Trial Outcomes & Findings for Tusamitamab Ravtansine Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors (NCT NCT04659603)

Last Updated: 2025-10-01

Results Overview

ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. CR was defined as disappearance of all target and non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)

Results posted on

2025-10-01

Participant Flow

The study was conducted at 31 centers in 10 countries. A total of 55 participants were screened from 29 March 2021 to 27 November 2023, of which 5 were screen failures. Screen failures were mainly due to not meeting the eligibility criteria.

Total 50 participants enrolled to receive tusamitamab ravtansine as single agent treatment (Cohorts A, B) or in combination with gemcitabine (Cohort C). All participants received the same dose in the respective Cohorts. The study was terminated due to the discontinuation of the overall development program of tusamitamab ravtansine by the Sponsor.

Participant milestones

Participant milestones
Measure	Cohort A: Metastatic Breast Cancer (mBC) Participants with mBC received an intravenous (IV) infusion of tusamitamab ravtansine at a loading dose of 170 milligram per square meter (mg/m\^2) on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 every 2 weeks (Q2W) from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: Metastatic Pancreatic Adenocarcinoma (mPAC) Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: Metastatic Pancreatic Adenocarcinoma (mPAC) Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 every 4 weeks (Q4W) until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Overall Study STARTED	6	28	16
Overall Study COMPLETED	6	23	13
Overall Study NOT COMPLETED	0	5	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort B: Metastatic Pancreatic Adenocarcinoma (mPAC) Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: Metastatic Pancreatic Adenocarcinoma (mPAC) Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 every 4 weeks (Q4W) until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Overall Study Study terminated by sponsor	0	2
Overall Study Withdrawal by Subject	5	0
Overall Study Not related to Coronavirus disease 2019	0	1

Baseline Characteristics

Tusamitamab Ravtansine Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: mBC n=6 Participants Participants with mBC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: mPAC n=28 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: mPAC n=16 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 Q4W until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Total n=50 Participants Total of all reporting groups
Age, Continuous	47.2 years STANDARD_DEVIATION 7.3 • n=99 Participants	63.8 years STANDARD_DEVIATION 11.8 • n=107 Participants	65.0 years STANDARD_DEVIATION 7.9 • n=206 Participants	62.2 years STANDARD_DEVIATION 11.5 • n=157 Participants
Sex: Female, Male Female	6 Participants n=99 Participants	18 Participants n=107 Participants	7 Participants n=206 Participants	31 Participants n=157 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	10 Participants n=107 Participants	9 Participants n=206 Participants	19 Participants n=157 Participants
Race/Ethnicity, Customized White	4 Participants n=99 Participants	19 Participants n=107 Participants	15 Participants n=206 Participants	38 Participants n=157 Participants
Race/Ethnicity, Customized Asian	1 Participants n=99 Participants	2 Participants n=107 Participants	1 Participants n=206 Participants	4 Participants n=157 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=99 Participants	4 Participants n=107 Participants	0 Participants n=206 Participants	4 Participants n=157 Participants
Race/Ethnicity, Customized Not reported	1 Participants n=99 Participants	3 Participants n=107 Participants	0 Participants n=206 Participants	4 Participants n=157 Participants

PRIMARY outcome

Timeframe: From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)

Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered.

Outcome measures

Outcome measures
Measure	Cohort A: mBC n=6 Participants Participants with mBC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: mPAC n=28 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: mPAC n=16 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 Q4W until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Objective Response Rate (ORR)	0 percentage of participants Interval 0.0 to 45.93	3.6 percentage of participants Interval 0.09 to 18.35	31.3 percentage of participants Interval 11.02 to 58.66

PRIMARY outcome

Timeframe: Cycle 1 (28 days)

Population: DLT-evaluable population (Cohort C Part 1) included participants who received 1 cycle with at least 80% of the intended dose for both tusamitamab ravtansine at each of the first 2 infusions and gemcitabine at each of the 3 first infusions unless they discontinued the study treatment before the end of Cycle 1 due to a DLT.

The following adverse events (AEs) that occurred during the first cycle of treatment, unless due to disease progression or to a cause obviously unrelated to study treatment, were considered DLTs: 1. Hematological abnormalities: grade 4 neutropenia for 7 or more consecutive days, grade 3 to 4 neutropenia complicated by fever or microbiologically or radiographically documented infection, grade greater than or equal to (≥) 3 thrombocytopenia associated with clinically significant bleeding requiring clinical intervention; 2. Non-hematological abnormalities: grade 4 non-hematologic AE, grade ≥3 keratopathy. In addition, any other AE that the recruiting Investigators and Sponsor deemed to be dose limiting, regardless of its grade, was also considered as DLT.

Outcome measures

Outcome measures
Measure	Cohort A: mBC n=3 Participants Participants with mBC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: mPAC Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: mPAC Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 Q4W until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Cohort C (Part 1): Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants	—	—

SECONDARY outcome

Timeframe: From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks

Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered.

An AE was defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A serious adverse event was defined as any AE that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via an authorized medicinal product. TEAEs were defined as AEs that developed, worsened, or became serious during the treatment-emergent period (defined as the period from the first study treatment administration to the last study treatment administration + 30 days).

Outcome measures

Outcome measures
Measure	Cohort A: mBC n=6 Participants Participants with mBC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: mPAC n=28 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: mPAC n=16 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 Q4W until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) TEAEs	6 Participants	28 Participants	16 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) TESAEs	0 Participants	16 Participants	9 Participants

SECONDARY outcome

Timeframe: From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks

Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered. Only those participants with data collected for the specified category are reported.

Blood samples were collected to determine the abnormalities in hematology/coagulation and clinical chemistry. Abnormality criteria was assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Hematological and coagulation parameters assessed were white blood cells, platelets, neutrophils, lymphocytes, and international normalized ratio. Clinical chemistry parameters assessed were albumin, sodium, potassium, calcium, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin. Only those categories in which at least 1 participant had \>2 grade worsening in laboratory abnormalities are reported.

Outcome measures

Outcome measures
Measure	Cohort A: mBC n=6 Participants Participants with mBC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: mPAC n=27 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: mPAC n=15 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 Q4W until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry Alanine aminotransferase increased	0 Participants	1 Participants	2 Participants
Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry Aspartate aminotransferase increased	0 Participants	1 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry Alkaline phosphatase increased	0 Participants	1 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry Total bilirubin increased	1 Participants	2 Participants	1 Participants
Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry Hypercalemia	0 Participants	0 Participants	2 Participants
Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry White blood cell decreased	0 Participants	1 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry Platelet count decreased	0 Participants	0 Participants	1 Participants
Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry Neutrophil count decreased	0 Participants	1 Participants	2 Participants
Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry Lymphocyte count decreased	0 Participants	0 Participants	2 Participants
Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry International normalized ratio increased	0 Participants	1 Participants	1 Participants
Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry Hypoalbuminemia	0 Participants	1 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry Hyponatremia	0 Participants	3 Participants	1 Participants
Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry Hyperkalemia	0 Participants	1 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry Hypocalemia	0 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)

Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered.

PFS was defined as the time from the date of first tusamitamab ravtansine administration to the date of the first documented disease progression according to RECIST v1.1 or death due to any cause, whichever came first. Disease progression was defined as unequivocal progression of existing non-target lesions; at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Outcome measures

Outcome measures
Measure	Cohort A: mBC n=6 Participants Participants with mBC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: mPAC n=28 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: mPAC n=16 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 Q4W until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Progression-free Survival (PFS)	3.71 months Interval 1.314 to NA indicates that the upper limit of 95% confidence interval (CI) was not estimable due to insufficient number of participants with events	1.87 months Interval 1.643 to 2.267	4.73 months Interval 1.873 to NA indicates that the upper limit of 95% CI was not estimable due to insufficient number of participants with events

SECONDARY outcome

Timeframe: From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)

Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered.

DCR was defined as the percentage of participants who achieved confirmed CR, confirmed PR or stable disease (SD) as per RECIST v1.1. CR was defined as disappearance of all target and non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum of diameters while on study.

Outcome measures

Outcome measures
Measure	Cohort A: mBC n=6 Participants Participants with mBC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: mPAC n=28 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: mPAC n=16 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 Q4W until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Disease Control Rate (DCR)	66.7 percentage of participants Interval 22.28 to 95.67	28.6 percentage of participants Interval 13.22 to 48.67	75.0 percentage of participants Interval 47.62 to 92.73

SECONDARY outcome

Timeframe: From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)

Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered. Only participants with response are analyzed. None of the participants in Cohort A had confirmed CR or PR; hence DOR could not be derived.

DOR was defined as the time from first documented evidence of confirmed CR or confirmed PR until progressive disease determined per RECIST v1.1 or death from any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Disease progression was defined as unequivocal progression of existing non-target lesions; at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Outcome measures

Outcome measures
Measure	Cohort A: mBC Participants with mBC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: mPAC n=1 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: mPAC n=5 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 Q4W until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Duration of Response (DOR)	—	4.11 months NA indicates that the upper and lower limit of 95% CI were not estimable due to insufficient number of participants with events.	7.26 months Interval 3.713 to NA indicates that the upper limit of 95% CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration [maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)]

Population: ATA population included all treated participants with at least 1 post-baseline ATA result.

Blood samples were collected for assessing the presence of ATA against tusamitamab ravtansine in plasma. The number of participants with treatment-emergent ATA i.e., either seroconverted (treatment-induced ATAs) or boosted their pre-existing ATA response (treatment-boosted ATAs) during the study are reported.

Outcome measures

Outcome measures
Measure	Cohort A: mBC n=6 Participants Participants with mBC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: mPAC n=21 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: mPAC n=4 Participants Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 Q4W until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Number of Participants With Treatment-emergent Anti-therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine	2 Participants	5 Participants	2 Participants

SECONDARY outcome

Timeframe: Cycle 1: Day 1: Start of infusion, end of infusion, 3, 72, 168, and 336 hours post-start of infusion (cycle duration: 28 days)

Population: Pharmacokinetic (PK) population included all treated participants with at least 1 post-baseline PK result with adequate documentation of dosing and sampling dates and times.

Blood samples were collected for the measurement of Cmax of tusamitamab ravtansine. Cmax was calculated using non-compartmental method.

Outcome measures

Outcome measures
Measure	Cohort A: mBC n=8 Participants Participants with mBC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: mPAC Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: mPAC Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 Q4W until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Cohort C: Maximum Concentration Observed After Infusion (Cmax) of Tusamitamab Ravtansine	88.3 microgram per milliliter (mcg/mL) Standard Deviation 17.8	—	—

SECONDARY outcome

Timeframe: Cycle 1: Day 1: Start of infusion, end of infusion, 3, 72, 168, and 336 hours post-start of infusion (cycle duration: 28 days)

Population: PK population included all treated participants with at least 1 post-baseline PK result with adequate documentation of dosing and sampling dates and times. Only those participants with data collected for this outcome measure are reported.

Blood samples were collected for the measurement of AUC0-14d of tusamitamab ravtansine. AUC0-14d was calculated using non-compartmental method.

Outcome measures

Outcome measures
Measure	Cohort A: mBC n=7 Participants Participants with mBC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: mPAC Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: mPAC Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 Q4W until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Cohort C: Area Under the Plasma Concentration Versus Time Curve Calculated Using the Trapezoidal Method From Time 0 to 14 Days (AUC0-14d) of Tusamitamab Ravtansine	473 day*mcg/mL Standard Deviation 85.7	—	—

SECONDARY outcome

Timeframe: Cycle 1: Days 1 and 8: Start of infusion, end of infusion, 0.25, 1, 1.5, and 2 hours post-start of infusion (cycle duration: 28 days)

Blood samples were collected for the measurement of CL of gemcitabine. CL was calculated using non-compartmental method.

Outcome measures

Outcome measures
Measure	Cohort A: mBC n=3 Participants Participants with mBC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: mPAC Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: mPAC Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 Q4W until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Cohort C: Total Body Clearance From Plasma (CL) of Gemcitabine	169 liter per hour Standard Deviation 93.8	—	—

SECONDARY outcome

Timeframe: Cycle 1: Days 1 and 8: Start of infusion, end of infusion, 0.25, 1, 1.5, and 2 hours post-start of infusion (cycle duration: 28 days)

Blood samples were collected for the measurement of Cmax of dFdU. Cmax was calculated using non-compartmental method.

Outcome measures

Outcome measures
Measure	Cohort A: mBC n=3 Participants Participants with mBC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: mPAC Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: mPAC Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 Q4W until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Cohort C: Cmax of Gemcitabine Metabolite (dFdU)	31.4 mcg/mL Standard Deviation 7.27	—	—

Adverse Events

Cohort A: mBC

Serious events: 0 serious events

Other events: 6 other events

Deaths: 4 deaths

Cohort B: mPAC

Serious events: 16 serious events

Other events: 23 other events

Deaths: 21 deaths

Cohort C: mPAC

Serious events: 9 serious events

Other events: 14 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER

Measure	Cohort A: mBC n=6 participants at risk Participants with mBC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort B: mPAC n=28 participants at risk Participants with mPAC received an IV infusion of tusamitamab ravtansine at a loading dose of 170 mg/m\^2 on Day 1 of Cycle 1 (cycle duration: 2 weeks), followed by 100 mg/m\^2 Q2W from Cycle 2 until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.	Cohort C: mPAC n=16 participants at risk Participants with mPAC received an IV infusion of tusamitamab ravtansine at an initial loading dose of 170 mg/m\^2 on Day 1, followed by 100 mg/m\^2 Q2W along with gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 Q4W until documented disease progression, unacceptable toxicity, new anticancer therapy initiation, or the participant's or Investigator's decision to stop the treatment.
Infections and infestations Biliary Tract Infection	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Infections and infestations Device Related Infection	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Infections and infestations Diarrhoea Infectious	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Infections and infestations Pneumonia Aspiration	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	6.2% 1/16 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Infections and infestations Sepsis	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Infections and infestations Urinary Tract Infection	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	6.2% 1/16 • Number of events 2 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Infections and infestations Urosepsis	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/28 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	6.2% 1/16 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Nervous system disorders Ischaemic Cerebral Infarction	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/28 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	6.2% 1/16 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Gastrointestinal disorders Abdominal Pain	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Gastrointestinal disorders Abdominal Pain Upper	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Gastrointestinal disorders Duodenal Obstruction	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Gastrointestinal disorders Duodenal Stenosis	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Gastrointestinal disorders Gastric Dilatation	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/28 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	6.2% 1/16 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Gastrointestinal disorders Gastritis Erosive	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Gastrointestinal disorders Ileus	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/28 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	6.2% 1/16 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Gastrointestinal disorders Intestinal Obstruction	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/28 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	6.2% 1/16 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Gastrointestinal disorders Intestinal Perforation	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/28 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	6.2% 1/16 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Gastrointestinal disorders Small Intestinal Perforation	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/28 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	6.2% 1/16 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Hepatobiliary disorders Biliary Obstruction	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/28 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	6.2% 1/16 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Hepatobiliary disorders Cholangitis	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Hepatobiliary disorders Cholangitis Acute	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Hepatobiliary disorders Cholecystitis	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Hepatobiliary disorders Jaundice Cholestatic	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
General disorders Complication Associated With Device	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/28 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	6.2% 1/16 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
General disorders Disease Progression	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	21.4% 6/28 • Number of events 6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	6.2% 1/16 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
General disorders Pain	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	3.6% 1/28 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/16 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.
Injury, poisoning and procedural complications Radiation Osteitis	0.00% 0/6 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	0.00% 0/28 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.	6.2% 1/16 • Number of events 1 • From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks. Analysis was performed on all-treated population.