Pembrolizumab + Lenvatinib for Bladder Cancer

Recruiting in Palo Alto (17 mi)

+193 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Merck Sharp & Dohme Corp.

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of lenvatinib (MK-7902/E7080) in combination with pembrolizumab (MK-3475) in the treatment of cisplatin-ineligible participants with a Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10, or in participants ineligible for any platinum-containing chemotherapy regardless of CPS, with advanced/unresectable or metastatic urothelial carcinoma (UC). The primary hypotheses for this study are that: 1. Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR), and 2. Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Overall Survival (OS). With Amendment 3 (effective: September \[Sep\]-24-2021) participants discontinued lenvatinib and placebo; participants who remained on treatment in the study arms received open-label pembrolizumab. With Amendment 3 the external Data Monitoring Committee was discontinued. With Amendment 4 (effective: December-5-2022) Second Course will no longer be offered. Any participant receiving Second Course treatment prior to initiation of Amendment 4 will be able to complete treatment as planned. With Amendment 4 study participation will end after the final administration of pembrolizumab. Participants who either complete 35 administrations of pembrolizumab or discontinue pembrolizumab will discontinue from the study following the safety follow-up visit. AEs and spontaneously reported pregnancies will be reported and followed per protocol. All participants in efficacy follow-up prior to initiation of Amendment 4 will stop efficacy assessments and be discontinued from the study. All participants in survival follow-up prior to initiation of Amendment 4 are considered to have completed the study and should have a final survival contact. The overall study ends when the last participant completes the last study-related contact or visit, withdraws from the study, or is lost to follow-up.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with advanced or metastatic urothelial carcinoma who can't have cisplatin-based chemotherapy. They must have a specific level of PD-L1 protein expression, be able to provide tissue samples, and not be pregnant or breastfeeding. Participants need controlled blood pressure, adequate organ function, and no severe hearing loss or neuropathy.

Inclusion Criteria

I have moderate to severe numbness, tingling, or pain in my hands or feet.

I have moderate to severe hearing loss.

My blood pressure is under control.

See 17 more

Exclusion Criteria

I had radiotherapy for cancer spread without certain drugs, except for bone treatment, within the last 3 weeks.

I have been diagnosed with HIV.

My condition can be treated with the goal of curing it.

See 24 more

Treatment Details

Interventions

Lenvatinib (Tyrosine Kinase Inhibitor)
Pembrolizumab (Monoclonal Antibodies)

Trial OverviewThe study tests the effectiveness and safety of combining lenvatinib with pembrolizumab versus pembrolizumab with a placebo in treating bladder cancer. The main goals are to see if this combination improves survival without disease progression and overall survival time.

Participant Groups

2Treatment groups

Experimental Treatment

Active Control

Group I: Pembrolizumab + LenvatinibExperimental Treatment2 Interventions

Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to \~2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) until progressive disease or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinue lenvatinib and participants who remain on treatment will receive open label pembrolizumab only, at the same dose and schedule (IV 200 mg on Day 1 of each 21-Day cycle for up to 35 cycles \[up to \~2 years\]).

Group II: Pembrolizumab + PlaceboActive Control2 Interventions

Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to \~2 years) PLUS placebo for lenvatinib via oral capsule QD until progressive disease or discontinuation. With protocol amendment 3 (effective: Sep-24-2021), participants discontinue placebo and participants who remain on treatment will receive open label pembrolizumab only, at the same dose and schedule (IV 200 mg on Day 1 of each 21-Day cycle for up to 35 cycles \[up to \~2 years\]).