Trial Outcomes & Findings for Trial of Pembrolizumab in Cancer of Unknown Primary (NCT NCT03752333)

Last Updated: 2026-05-04

Results Overview

The Response Evaluation Criteria in Solid Tumours (RECIST) criteria v1.1. classifies response based on the assessment of target and non-target lesions on CT scans as: Complete Response (CR): requires all of: * disappearance of all target and non-target lesions * pathological lymph nodes must have reduced to \<10 mm in short axis * no new lesions Partial Response (PR): requires all of: * at least 30% decrease in sum of diameters (SOD) of target lesions compared to baseline sum diameters * non-progressive disease of non-target lesions * no new lesions Progressive Disease (PD): either one of: * any new lesions * at least 20% relative and 5 mm absolute increase of SOD of target lesions compared to smallest SOD ever recorded for the patient Stable Disease (SD): not meeting criteria for PD or PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

From the start of the study treatment until the end of treatment, an average of 6-8 months.

Results posted on

2026-05-04

Participant Flow

A substantial amendment in January 2022 has formally closed Cohort 2, due to the significant challenges in recruitment caused by the ongoing COVID-19 pandemic as well as associated clinical factors. Accordingly, the trial sought to expand on and analyse as a single cohort.

Participant milestones

Participant milestones
Measure	Pembrolizumab All trial treatments are administered on an outpatient basis. Pembrolizumab 200 mg is administered as a 30 minute IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min). Pembrolizumab: Pembrolizumab has high affinity and potent receptor blocking activity for PD-1, based on preclinical in vitro data. Pembrolizumab has an acceptable preclinical and clinical safety profile and is in clinical development as an IV immunotherapy for advanced malignancies. The PD-1 pathway represents a major immune control switch, which may be engaged by tumour cells to overcome active T-cell immune surveillance. Pembrolizumab is a potent and highly selective humanized mAb of the Immunoglobulin (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances functional activity of the target lymphocytes to facilitate tumor regression and ultimately immune rejection.
Overall Study STARTED	35
Overall Study COMPLETED	35
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

One participant has missing quality of life data.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab n=35 Participants All trial treatments will be administered on an outpatient basis. Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min). Pembrolizumab: Pembrolizumab has high affinity and potent receptor blocking activity for PD-1, based on preclinical in vitro data. Pembrolizumab has an acceptable preclinical and clinical safety profile and is in clinical development as an IV immunotherapy for advanced malignancies. The PD-1 pathway represents a major immune control switch, which may be engaged by tumour cells to overcome active T-cell immune surveillance. Pembrolizumab is a potent and highly selective humanized mAb of the Immunoglobulin (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances functional activity of the target lymphocytes to facilitate tumor regression and ultimately immune rejection.
Age, Continuous	58 years n=35 Participants
Sex: Female, Male Female	21 Participants n=35 Participants
Sex: Female, Male Male	14 Participants n=35 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=35 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=35 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=35 Participants
Region of Enrollment United Kingdom	35 participants n=35 Participants
Histology Poorly differentiated adenocarcinoma or carcinoma	11 Participants n=35 Participants
Histology Well or Moderately Differentiated Adenocarcinoma	9 Participants n=35 Participants
Histology Undifferentiated Adenocarcinoma or Carcinoma	8 Participants n=35 Participants
Histology Squamous cell carcinoma	7 Participants n=35 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1	30 Participants n=35 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2	5 Participants n=35 Participants
EORTC QLQ-C30 Summary Score	70 units on a scale STANDARD_DEVIATION 18 • n=34 Participants • One participant has missing quality of life data.

PRIMARY outcome

Timeframe: From the start of the study treatment until the end of treatment, an average of 6-8 months.

Population: The Intention-to-Treat (ITT) Population.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=35 Participants All trial treatments are administered on an outpatient basis. Pembrolizumab 200 mg is administered as a 30 minute IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min). Pembrolizumab: Pembrolizumab has high affinity and potent receptor blocking activity for PD-1, based on preclinical in vitro data. Pembrolizumab has an acceptable preclinical and clinical safety profile and is in clinical development as an IV immunotherapy for advanced malignancies. The PD-1 pathway represents a major immune control switch, which may be engaged by tumour cells to overcome active T-cell immune surveillance. Pembrolizumab is a potent and highly selective humanized mAb of the Immunoglobulin (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances functional activity of the target lymphocytes to facilitate tumor regression and ultimately immune rejection.
Overall Response Rate (ORR) by RECIST Criteria v1.1 in the Second-line & First-line Setting. Complete Response (CR)	0 Participants
Overall Response Rate (ORR) by RECIST Criteria v1.1 in the Second-line & First-line Setting. Partial Response (PR)	4 Participants
Overall Response Rate (ORR) by RECIST Criteria v1.1 in the Second-line & First-line Setting. Stable Disease (SD)	9 Participants
Overall Response Rate (ORR) by RECIST Criteria v1.1 in the Second-line & First-line Setting. Progressive Disease (PD)	13 Participants
Overall Response Rate (ORR) by RECIST Criteria v1.1 in the Second-line & First-line Setting. Not Evaluable (NE)	9 Participants

SECONDARY outcome

Timeframe: 6-8 months, based on average length of treatment per patient

Population: The Safety Analysis Population includes all patients who received at least one dose of the trial treatment.

The number of patients with any recorded adverse events (AE) defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the trial. The incidence proportion or cumulative incidence is the percentage (%) of patients developing new AEs out of the total number at risk followed during that time frame.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=35 Participants All trial treatments are administered on an outpatient basis. Pembrolizumab 200 mg is administered as a 30 minute IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min). Pembrolizumab: Pembrolizumab has high affinity and potent receptor blocking activity for PD-1, based on preclinical in vitro data. Pembrolizumab has an acceptable preclinical and clinical safety profile and is in clinical development as an IV immunotherapy for advanced malignancies. The PD-1 pathway represents a major immune control switch, which may be engaged by tumour cells to overcome active T-cell immune surveillance. Pembrolizumab is a potent and highly selective humanized mAb of the Immunoglobulin (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances functional activity of the target lymphocytes to facilitate tumor regression and ultimately immune rejection.
Incidence Proportion of Adverse Events up to 8 Weeks After the Last Dose of Pembrolizumab in the Second Line Setting	34 Participants

SECONDARY outcome

Timeframe: 6-8 months (based on average length of treatment per patient)

Population: This is the number of participants with Performance Status score equal to 2 at baseline. Performance Status (PS) is measured according to the Eastern Cooperative Oncology Group (ECOG) Performance status score, which is a scale from 0 (fully active) to 4 (death) to grade how well the participant is, their cancer related symptoms, and what activities they are able to do.

The number of patients whose Performance Status was equal to two at baseline, with any recorded adverse events (AE) defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the trial. The incidence proportion or cumulative incidence is the percentage (%) of patients developing new AEs out of the total number at risk followed during that time frame.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=5 Participants All trial treatments are administered on an outpatient basis. Pembrolizumab 200 mg is administered as a 30 minute IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min). Pembrolizumab: Pembrolizumab has high affinity and potent receptor blocking activity for PD-1, based on preclinical in vitro data. Pembrolizumab has an acceptable preclinical and clinical safety profile and is in clinical development as an IV immunotherapy for advanced malignancies. The PD-1 pathway represents a major immune control switch, which may be engaged by tumour cells to overcome active T-cell immune surveillance. Pembrolizumab is a potent and highly selective humanized mAb of the Immunoglobulin (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances functional activity of the target lymphocytes to facilitate tumor regression and ultimately immune rejection.
Incidence of Adverse Events up to 8 Weeks After the Last Dose of Pembrolizumab in Performance Status 2 (PS2) Patients in Any Setting	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months (post study completion)

This would be a retrospective analysis of blood samples collected for future research purposes only. Research bloods will be used to examine DNA and measure various blood biomarkers. These biomarkers may predict possible response to study treatment. As these samples are being taken before, during and after treatment, they will help us understand how the study treatments work. This will also enable us to learn whether or not the treatments have the desired effect, and to understand if these effects may be beneficial for the treatment of cancer of unknown primary (CUP). This information may also be used to develop and test other new treatments in the future. The panel of potential biomarkers against which the blood plasma will be tested has not been established yet. Information gained from this research component is not directly beneficial to patients taking part in this clinical trial.

Outcome measures

Outcome data not reported

Adverse Events

Pembrolizumab

Serious events: 20 serious events

Other events: 15 other events

Deaths: 27 deaths

Serious adverse events

Serious adverse events
Measure	Pembrolizumab n=35 participants at risk All trial treatments are administered on an outpatient basis. Pembrolizumab 200 mg is administered as a 30 minute IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min). Pembrolizumab: Pembrolizumab has high affinity and potent receptor blocking activity for PD-1, based on preclinical in vitro data. Pembrolizumab has an acceptable preclinical and clinical safety profile and is in clinical development as an IV immunotherapy for advanced malignancies. The PD-1 pathway represents a major immune control switch, which may be engaged by tumour cells to overcome active T-cell immune surveillance. Pembrolizumab is a potent and highly selective humanized mAb of the Immunoglobulin (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances functional activity of the target lymphocytes to facilitate tumor regression and ultimately immune rejection.
Investigations Alanine aminotransferase increased	5.7% 2/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Metabolism and nutrition disorders Hyponatraemia	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Psychiatric disorders Confusion	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Gastrointestinal disorders Diarrhoea	5.7% 2/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Cardiac disorders Pericardial effusion	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Cardiac disorders Peripheral swelling	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Nervous system disorders Hypoaesthesia	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Investigations Haemoglobin decreased	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.9% 1/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Gastrointestinal disorders Abdominal pain	5.7% 2/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Nervous system disorders Headache	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Gastrointestinal disorders Vomiting	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Infections and infestations Abdominal infection	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Gastrointestinal disorders Small intestinal obstruction	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Surgical and medical procedures Complication associated with device	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Infections and infestations Wound infection	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Investigations Body temperature increased	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Cardiac disorders Dyspnoea	2.9% 1/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Infections and infestations Measles	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Infections and infestations Pneumonia	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Social circumstances Pregnancy of partner	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
General disorders Pyrexia	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Infections and infestations Urinary tract infection	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Infections and infestations Groin infection	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Renal and urinary disorders Urinary Incontinence	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Endocrine disorders Adrenal insufficiency	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Metabolism and nutrition disorders Hypercalcaemia	2.9% 1/35 • Number of events 1 • From the start of the study treatment until the end of treatment, an average of 6-8 months.

Other adverse events

Other adverse events
Measure	Pembrolizumab n=35 participants at risk All trial treatments are administered on an outpatient basis. Pembrolizumab 200 mg is administered as a 30 minute IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min). Pembrolizumab: Pembrolizumab has high affinity and potent receptor blocking activity for PD-1, based on preclinical in vitro data. Pembrolizumab has an acceptable preclinical and clinical safety profile and is in clinical development as an IV immunotherapy for advanced malignancies. The PD-1 pathway represents a major immune control switch, which may be engaged by tumour cells to overcome active T-cell immune surveillance. Pembrolizumab is a potent and highly selective humanized mAb of the Immunoglobulin (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances functional activity of the target lymphocytes to facilitate tumor regression and ultimately immune rejection.
General disorders Oedema	5.7% 2/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Musculoskeletal and connective tissue disorders Pain in extremity	5.7% 2/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Skin and subcutaneous tissue disorders Pruritus	5.7% 2/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Infections and infestations Sepsis	5.7% 2/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Investigations Weight decreased	5.7% 2/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Infections and infestations Herpes zoster	5.7% 2/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Metabolism and nutrition disorders Hyperkalaemia	5.7% 2/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
General disorders Fatigue	40.0% 14/35 • Number of events 22 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Gastrointestinal disorders Abdominal pain	25.7% 9/35 • Number of events 9 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Musculoskeletal and connective tissue disorders Arthralgia	14.3% 5/35 • Number of events 9 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Gastrointestinal disorders Constipation	22.9% 8/35 • Number of events 9 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Metabolism and nutrition disorders Decreased appetite	17.1% 6/35 • Number of events 8 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Gastrointestinal disorders Vomiting	22.9% 8/35 • Number of events 8 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.4% 4/35 • Number of events 7 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Gastrointestinal disorders Ascites	11.4% 4/35 • Number of events 6 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Respiratory, thoracic and mediastinal disorders Cough	8.6% 3/35 • Number of events 6 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Endocrine disorders Hypothyroidism	17.1% 6/35 • Number of events 6 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Gastrointestinal disorders Nausea	14.3% 5/35 • Number of events 6 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Infections and infestations Oral candidiasis	11.4% 4/35 • Number of events 6 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Gastrointestinal disorders Abdominal distension	8.6% 3/35 • Number of events 5 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
General disorders Oedema peripheral	8.6% 3/35 • Number of events 5 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
General disorders Pyrexia	14.3% 5/35 • Number of events 5 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Skin and subcutaneous tissue disorders Rash	11.4% 4/35 • Number of events 5 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Blood and lymphatic system disorders Anaemia	8.6% 3/35 • Number of events 4 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Investigations Blood bilirubin increased	8.6% 3/35 • Number of events 4 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Metabolism and nutrition disorders Hypercalcaemia	8.6% 3/35 • Number of events 4 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Nervous system disorders Neuropathy peripheral	11.4% 4/35 • Number of events 4 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Infections and infestations Urinary tract infection	8.6% 3/35 • Number of events 4 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Renal and urinary disorders Acute kidney injury	5.7% 2/35 • Number of events 3 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Musculoskeletal and connective tissue disorders Back pain	8.6% 3/35 • Number of events 3 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.7% 2/35 • Number of events 3 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Skin and subcutaneous tissue disorders Dermatitis	5.7% 2/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Skin and subcutaneous tissue disorders Dry skin	5.7% 2/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.7% 2/35 • Number of events 2 • From the start of the study treatment until the end of treatment, an average of 6-8 months.

Additional Information

Professor Harpreet Wasan (Chief Investigator)

Imperial College London

Phone: +44(0) 20 8383 3089

Email: [email protected]; [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place