Pembrolizumab + Lenvatinib with/without FMT for Melanoma

Recruiting in Palo Alto (17 mi)

Dr. Diwakar Davar, MD - Pittsburgh, PA ...

Overseen byDiwakar Davar, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Diwakar Davar

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

In this is a randomized phase II study the addition of hd-FMT (healthy donor fecal-microbiota transplant) to pembrolizumab /lenvatinib in PD-1 R/R melanoma will be evaluated over a 104-week period in patients with anti-PD-1 R/R disease. Patients with PD-1 refractory advanced melanoma are eligible to enroll, excluding patients with prior lenvatinib (or other TKI) exposure. Intestinal microbiome composition mediates response to anti-PD-1 by affecting systemic inflammatory tone.

Eligibility Criteria

This trial is for adults with advanced melanoma that has not responded to anti-PD-1 therapy. They must have stable, treated brain metastases if present, agree to use contraception, and be willing to undergo endoscopic FMT. Excluded are those with certain types of melanoma (uveal, mucosal), recent major surgery, severe allergies or gastrointestinal conditions affecting drug absorption, unmanaged side effects from previous treatments, active infections including COVID-19 or hepatitis B/C virus infection.

Inclusion Criteria

You have a disease that can be measured using specific guidelines.

I have skin melanoma or melanoma of unknown primary, not uveal, mucosal, or acral-lentiginous melanoma.

I agree to follow the study's rules for using contraception and not donate sperm for 120 days after the last treatment.

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Exclusion Criteria

You have severe allergies to certain foods like shellfish, nuts, or seafood.

A WOCBP who has a positive urine pregnancy test at Screening (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

You have a severe allergic reaction (Grade 3 or higher) to anti-PD(L)1 inhibitor.

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Treatment Details

Interventions

Lenvatinib (Other)
Pembrolizumab (Immunotherapy)
Responder-Derived FMT (Other)

Trial OverviewThe study tests whether adding Responder-Derived Fecal Microbiota Transplantation (R-FMT) to the combination of Pembrolizumab and Lenvatinib improves outcomes in patients whose melanoma hasn't responded to PD-1 inhibitors. It's a randomized phase II trial over 104 weeks where participants' intestinal microbiome composition is considered as a mediator for their response.

Participant Groups

2Treatment groups

Experimental Treatment

Active Control

Group I: hdFMT + pembrolizumab/lenvatinib (Arm A)Experimental Treatment3 Interventions

* Pembrolizumab will be administered at 200 mg every 3 weeks (Q3W) as a 30-minute IV infusion (treatment intervals may be increased due to toxicity as described). * Lenvatinib will be administered at 20 mg daily. * hdFMT (induction) will be administered at C1D1 and C4D1 via colonoscopy or oral capsules * hdFMT (maintenance) will be repeated every 9 weeks starting with C4D1 via sigmodoscopy or oral capsules

Group II: pembrolizumab/lenvatinib (Arm B)Active Control2 Interventions

Lenvatinib is already approved in United States, European Union, European Union for the following indications:

🇺🇸 Approved in United States as Lenvima for: