Trial Outcomes & Findings for Pembrolizumab in Patients With Poor-Prognosis Carcinoma of Unknown Primary Site (CUP) (NCT NCT03391973)

NCT ID: NCT03391973

Last Updated: 2026-07-02

Results Overview

The objective response rate will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per RECIST v1.1, tumor response was assessed using MRI or CT imaging. Complete Response (CR) was defined as disappearance of all target lesions; Partial Response (PR) as a ≥30% decrease in the sum of diameters of target lesions from baseline; Stable Disease (SD) as neither sufficient tumor shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD); and PD as a ≥20% increase in the sum of diameters of target lesions or the appearance of new lesions. Disease Control Rate (DCR) was defined as the proportion of participants who achieved CR, PR, or SD as their best overall response during the assessment period, reflecting the ability of treatment to prevent disease progression. The RECIST median duration of response is the time, measured from the first date of CR or PR to PD or death.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

Within 3 years

Results posted on

2026-07-02

Participant Flow

Participant milestones

Participant milestones
Measure	Arm 1 - Pembrolizumab Arm 1 - Pembrolizumab injection dosed at 200 mg given Q3 weeks by IV infusion on Day 1 of each 3 week cycle. Pembrolizumab Injection: Pembrolizumab 200 mg will be administered as a 30 minute IV infusion Q3W.
Overall Study STARTED	33
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1 - Pembrolizumab Arm 1 - Pembrolizumab injection dosed at 200 mg given Q3 weeks by IV infusion on Day 1 of each 3 week cycle. Pembrolizumab Injection: Pembrolizumab 200 mg will be administered as a 30 minute IV infusion Q3W.
Overall Study Lack of Efficacy	2
Overall Study Physician Decision	2
Overall Study Adverse Event	1
Overall Study Development intercurrent illness preventing ongoing treatment	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1 - Pembrolizumab n=33 Participants Pembrolizumab injection dosed at 200 mg given Q3 weeks by IV infusion on Day 1 of each 3 week cycle.
Age, Customized Age	64 years n=33 Participants
Sex: Female, Male Female	14 Participants n=33 Participants
Sex: Female, Male Male	19 Participants n=33 Participants
ECOG 0	5 Participants n=33 Participants
ECOG 1	28 Participants n=33 Participants
Histology Adenocarcinoma	22 Participants n=33 Participants
Histology Squamous Cell Carcinoma	2 Participants n=33 Participants
Histology Poorly Differentiated	8 Participants n=33 Participants
Histology Other	1 Participants n=33 Participants
Sites of Metastatic Disease Lung	14 Participants n=33 Participants
Sites of Metastatic Disease Liver	23 Participants n=33 Participants
Sites of Metastatic Disease Bone	8 Participants n=33 Participants
Sites of Metastatic Disease Lymph Nodes	20 Participants n=33 Participants
Sites of Metastatic Disease Skin/soft tissues	1 Participants n=33 Participants
Sites of Metastatic Disease Genitourinary	1 Participants n=33 Participants
Sites of Metastatic Disease Other	8 Participants n=33 Participants
Number of Metastatic Sites 1	5 Participants n=33 Participants
Number of Metastatic Sites 2	12 Participants n=33 Participants
Number of Metastatic Sites 3 or more	16 Participants n=33 Participants
Baseline Endoscopy Baseline upper and lower endoscopy	22 Participants n=33 Participants
Baseline Endoscopy Baseline upper and no lower endoscopy	2 Participants n=33 Participants
Baseline Endoscopy Baseline lower and no upper endoscopy	2 Participants n=33 Participants
Baseline Endoscopy No endoscopy	7 Participants n=33 Participants
MMR MMR Proficient	6 Participants n=33 Participants
MMR MMR Deficient	2 Participants n=33 Participants
MMR MMR status unknown/not done	25 Participants n=33 Participants
Elevated LDH at baseline	10 Participants n=33 Participants
Baseline PET Baseline PET	3 Participants n=33 Participants
Baseline PET no PET	30 Participants n=33 Participants

PRIMARY outcome

Timeframe: Within 3 years

Population: 33 patients were enrolled and 27 were evaluable. Subjects enrolled were considered evaluable for response if they received study treatment and did not discontinue from study treatment before completion of a response evaluation period (at 9 weeks)

Outcome measures

Outcome measures
Measure	Arm 1 - Pembrolizumab n=27 Participants Pembrolizumab injection dosed at 200 mg given Q3 weeks by IV infusion on Day 1 of each 3 week cycle.
Number of Participants That Develop an Objective Response to Treatment (Objective Response Rate, ORR). Objective Response Rate	3 Participants
Number of Participants That Develop an Objective Response to Treatment (Objective Response Rate, ORR). Stable Disease	11 Participants
Number of Participants That Develop an Objective Response to Treatment (Objective Response Rate, ORR). Complete Response	1 Participants
Number of Participants That Develop an Objective Response to Treatment (Objective Response Rate, ORR). Partial Response	2 Participants
Number of Participants That Develop an Objective Response to Treatment (Objective Response Rate, ORR). Progressive Disease	13 Participants
Number of Participants That Develop an Objective Response to Treatment (Objective Response Rate, ORR). Disease Control Rate	14 Participants

PRIMARY outcome

Timeframe: Within 3 years

The duration of response and disease control will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per RECIST v1.1, tumor response was assessed using MRI or CT imaging. Complete Response (CR) was defined as disappearance of all target lesions; Partial Response (PR) as a ≥30% decrease in the sum of diameters of target lesions from baseline; Stable Disease (SD) as neither sufficient tumor shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease; and Progressive Disease (PD) as a ≥20% increase in the sum of diameters of target lesions (with an absolute increase of at least 5 mm) or the appearance of new lesions. Disease Control Rate (DCR) was defined as the proportion of participants who achieved CR, PR, or SD as their best overall response during the assessment period, reflecting the ability of treatment to prevent disease progression. The Duration of Response is the time, measured from the first date of CR or PR to PD or death.

Outcome measures

Outcome measures
Measure	Arm 1 - Pembrolizumab n=27 Participants Pembrolizumab injection dosed at 200 mg given Q3 weeks by IV infusion on Day 1 of each 3 week cycle.
Duration of Response and Disease Control Median Duration of Response	22.12 Months Interval 16.33 to The upper bound of the 95% confidence interval could not be calculated because the event threshold has not yet been reached in the data - meaning the study follow-up period is still ongoing and a reliable upper limit cannot be determined at this time. At the time of study closure (i.e. no further study data collection), 1 participant did not reach PD or death.
Duration of Response and Disease Control Median Duration of Disease Control	6.39 Months Interval 3.09 to 8.44

PRIMARY outcome

Timeframe: Within 3 years

Treatment related adverse events will be assessed using CTCAE v4.0.

Outcome measures

Outcome measures
Measure	Arm 1 - Pembrolizumab n=27 Participants Pembrolizumab injection dosed at 200 mg given Q3 weeks by IV infusion on Day 1 of each 3 week cycle.
Incidence of Treatment-related Adverse Events (TRAEs) Serious Adverse Events (possibly related)	2 Number of Events
Incidence of Treatment-related Adverse Events (TRAEs) Adverse Events (possibly related)	55 Number of Events

SECONDARY outcome

Timeframe: Within 4 years

OS is the time from treatment initiation to death due to any cause

Outcome measures

Outcome measures
Measure	Arm 1 - Pembrolizumab n=27 Participants Pembrolizumab injection dosed at 200 mg given Q3 weeks by IV infusion on Day 1 of each 3 week cycle.
The Overall Survival (OS) of Participants.	9.49 months Interval 3.84 to 14.72

SECONDARY outcome

Timeframe: Within 4 years

Progression is assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum recorded since treatment started (nadir), with an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Arm 1 - Pembrolizumab n=27 Participants Pembrolizumab injection dosed at 200 mg given Q3 weeks by IV infusion on Day 1 of each 3 week cycle.
The Progression Free Survival (PFS) of Participants.	2.98 months Interval 2.07 to 4.63

Adverse Events

Arm 1 - Pembrolizumab

Serious events: 2 serious events

Other events: 27 other events

Deaths: 26 deaths

Serious adverse events

Serious adverse events
Measure	Arm 1 - Pembrolizumab n=27 participants at risk Arm 1 - Pembrolizumab injection dosed at 200 mg given Q3 weeks by IV infusion on Day 1 of each 3 week cycle. Pembrolizumab Injection: Pembrolizumab 200 mg will be administered as a 30 minute IV infusion Q3W.
General disorders Fatigue, generalized weakness	3.7% 1/27 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Gastrointestinal disorders Fever, nausea, vomiting	3.7% 1/27 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.

Other adverse events

Other adverse events
Measure	Arm 1 - Pembrolizumab n=27 participants at risk Arm 1 - Pembrolizumab injection dosed at 200 mg given Q3 weeks by IV infusion on Day 1 of each 3 week cycle. Pembrolizumab Injection: Pembrolizumab 200 mg will be administered as a 30 minute IV infusion Q3W.
General disorders Dizziness	3.7% 1/27 • Number of events 1 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Eye disorders Epiphora	3.7% 1/27 • Number of events 1 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Skin and subcutaneous tissue disorders Hand food syndrome	3.7% 1/27 • Number of events 1 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Musculoskeletal and connective tissue disorders Joint Pain	22.2% 6/27 • Number of events 6 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
General disorders Fatigue/malaise/weakness	25.9% 7/27 • Number of events 7 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Skin and subcutaneous tissue disorders Rash	14.8% 4/27 • Number of events 4 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
General disorders Nausea	18.5% 5/27 • Number of events 5 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Skin and subcutaneous tissue disorders Pruritis	14.8% 4/27 • Number of events 4 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Respiratory, thoracic and mediastinal disorders Cough/Dyspnea	14.8% 4/27 • Number of events 4 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Gastrointestinal disorders Vomiting	11.1% 3/27 • Number of events 3 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
General disorders Anorexia/Decreased food intake	7.4% 2/27 • Number of events 2 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
General disorders Pain	3.7% 1/27 • Number of events 1 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Gastrointestinal disorders Diarrhea	7.4% 2/27 • Number of events 2 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
General disorders Fever	7.4% 2/27 • Number of events 2 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Nervous system disorders Headache	3.7% 1/27 • Number of events 1 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Renal and urinary disorders Dysuria/Urine changes	7.4% 2/27 • Number of events 2 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Endocrine disorders Adrenal Insufficiency	3.7% 1/27 • Number of events 1 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Nervous system disorders Confusion	3.7% 1/27 • Number of events 1 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Skin and subcutaneous tissue disorders Edema	3.7% 1/27 • Number of events 1 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Investigations Increased CRP	3.7% 1/27 • Number of events 1 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Musculoskeletal and connective tissue disorders Myalgias	3.7% 1/27 • Number of events 1 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.7% 1/27 • Number of events 1 • Serious and Other Adverse Events were monitored/assessed from the time that informed consent is signed until cessation of treatment or until the beginning of a new anti-neoplastic therapy, whichever occurs first, up to 3 years. All-cause Mortality was assessed for up to 4 years.

Additional Information

Jose Monzon

Cancer Care Alberta

Phone: 587-231-5102

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor to review and comment on public presentations and publications and may request reasonable delays to protect confidential or proprietary information.
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Restriction type: OTHER