Pembrolizumab Plus Lenvatinib in Combination with Belzutifan in Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Aug 2021 → ongoing

Decision date (initial)

2023-10-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Eisai · Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-503905-12-00

EudraCT number

2020-005007-40

WHO UTN

U1111-1288-3020

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Safety, Dose response, Therapy, Pharmacogenomic, Pharmacoeconomic, Pharmacokinetic

1. To assess the safety and tolerability of the combination of pembrolizumab and lenvatinib and belzutifan (Arm 1/triplet).
2. To evaluate the confirmed objective response rate (ORR) per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR).

Secondary objectives 6

1. To evaluate the duration of response (DOR) per RECIST 1.1 as assessed by BICR.
2. To evaluate disease control rate (DCR) per RECIST 1.1 by BICR.
3. To evaluate the progression-free survival (PFS) per RECIST 1.1 as assessed by BICR.
4. To evaluate the overall survival (OS)
5. To evaluate efficacy outcomes per hepatocellular carcinoma (HCC)-specific modified Response Criteria in Solid Tumors version 1.1 (mRECIST 1.1) (Cohort A) assessed by BICR.
6. To assess the safety and tolerability of the combination of pembrolizumab and lenvatinib (Arm 2/doublet) in Cohort G

Conditions and MedDRA coding

Liver cancer; Colon cancer; Pancreatic cancer; Bile Duct or Gallbladder cancer; Endometrial cancer; Esophageal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Diagnosis of one of the following advanced (unresectable and/or metastatic) solid tumors, documented by histopathology or cytopathology: Hepatocellular carcinoma (HCC), Colorectal cancer (CRC) (non-microsatellite instability-high [non-MSI-H]/deficient mismatch repair [dMMR]), Pancreatic ductal adenocarcinoma (PDAC), Biliary tract cancer (BTC) (includes intrahepatic, extrahepatic cholangiocarcinoma [CCA] and gall bladder cancer), Endometrial cancer (EC), Esophageal squamous cell carcinoma (ESCC)
2. Disease progression on or since the most recent treatment (does not apply to newly diagnosed unresectable or metastatic HCC or EC).
3. Measurable disease per RECIST v1.1 as assessed locally (by investigator) and verified by BICR
4. Submission of an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
5. HCC Specific Inclusion Criteria: No prior systemic chemotherapy, including anti-VEGF therapy, anti-programmed cell-death (PD-1)/PD-L1 or any systemic investigational anticancer agents for advanced/unresectable HCC (1L)
6. CRC ([non-MSI-H/dMMR) Specific Inclusion Criteria: Received at least 2 prior lines of systemic therapy for unresectable or metastatic disease which includes fluoropyrimidine, irinotecan and oxaliplatin
7. PDAC Specific Inclusion Criteria: Prior therapy with at least 1 (platinum or gemcitabine containing regimen) but no more than 2 prior systemic therapies for unresectable or metastatic pancreatic cancer
8. BTC Specific Inclusion Criteria: Received at least 1 prior line of systemic therapy (containing gemcitabine or fluoropyrimidine) for unresectable or metastatic disease
9. EC Specific Inclusion Criteria: Study treatment is for 1L therapy of EC and participants should not have received prior systemic chemotherapy. Exception: May have received 1 prior line of line of systemic platinum-based adjuvant and/or neoadjuvant chemotherapy in the setting of a curative-intent resection, if the recurrence occurred ≥6 months after the last dose of chemotherapy or may have received prior radiation with or without chemotherapy
10. ESCC Specific Inclusion Criteria: Have experienced radiographic or clinical progression on one prior line of standard systemic therapy (immune oncology (IO) naïve participants) or an anti-PD-1/PD-L1 (IO resistant participants)

Exclusion criteria 6

1. Unable to swallow orally administered medication or presence of a gastrointestinal (GI) disorder that may affect study intervention absorption
2. History of a second malignancy that is progressing or has required active treatment within 3 years
3. Presence of central nervous system (CNS) metastases and/or carcinomatous meningitis
4. Clinically significant cardiovascular disease within 6 months of first dose of study intervention
5. Moderate to severe hepatic impairment
6. Prior therapy with a PD-1, anti-PD-L1, anti-PD-L2 agent, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) or hypoxia-inducible factor 2α (HIF-2α). Note, this criteria does not apply to participants with immune oncology (IO) exposed ESCC.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Number of Participants in Lead-in Phase Who Experience at Least One Dose-limiting Toxicity (DLT)
2. Number of Participants in Arm 1/Triplet Who Experience at Least One Adverse Event (AE)
3. Number of Participants in Arm 1/Triplet Who Discontinue Study Treatment Due to an AE
4. Objective Response Rate Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

Secondary endpoints 10

1. Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
2. Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR
3. Progression-free Survival (PFS) Per RECIST 1.1 as Assessed by BICR
4. Overall Survival (OS)
5. ORR Per Modified Response Criteria in Solid Tumors Version 1.1 (mRECIST 1.1) for Hepatocellular Carcinoma (HCC) as Assessed by BICR
6. DOR Per mRECIST 1.1 for HCC as Assessed by BICR
7. DCR Per mRECIST 1.1 for HCC as Assessed by BICR
8. PFS Per mRECIST 1.1 for HCC as Assessed by BICR
9. Number of Participants in Arm 2/Doublet Who Experience at Least One AE
10. Number of Participants in Arm 2/Doublet Who Discontinue Study Treatment Due to an AE

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Girish Somala Naik

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Girish Somala Naik

Third parties 4

Locations

4 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 53 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications