Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Melanoma

What is the Purpose of this Study?

Substudies 02A, 02B, and 02C: To assess the safety and tolerability of investigational treatment combinations based on the proportion of participants with adverse events (AEs). Substudies 02A and 02B: To evaluate objective response rate (ORR) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). Substudy 02C: To evaluate pathological complete response (pCR) rate as assessed by central review of the pathology results.

Eligibility

* Has histologically or cytologically confirmed melanoma
* Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
* Has been untreated for advanced disease.
* Has provided a tumor biopsy

Inclusion Criteria:

* Has histologically or cytologically confirmed melanoma
* Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
* Has been untreated for advanced disease.
* Has provided a tumor biopsy
* If capable of producing sperm, male participants agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (7 days):
* Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR
* Uses contraception unless confirmed to be azoospermic
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
* Is not a WOCBP OR
* Is a WOCBP and Uses a contraceptive method that is highly effective, with low user dependency, or be abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
* MK-4280A: 120 days
* MK-1308A: 120 days
* MK-7684: 50 days
* MK-3475: 120 days
* Lenvatinib: 30 days
* ATRA: 30 days
* Has adequate organ function
* Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia and Grade 2 neuropathy)

Exclusion Criteria:

* Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days before the first dose of study intervention
* Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
* Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has ocular or mucosal melanoma
* Has an active autoimmune disease that has required systemic treatment in the past 2 years
* Has an active infection requiring systemic therapy
* Has known history of human immunodeficiency virus (HIV)
* Has history of Hepatitis B or known Hepatitis C virus infection
* Has a history of (noninfectious) pneumonitis
* Has a history of active tuberculosis (TB)
* Has received prior systemic anticancer therapy within 4 weeks prior to randomization
* Has received prior radiotherapy within 2 weeks of first dose of study intervention
* Has had major surgery \<3 weeks prior to first dose of study intervention
* Has received a live vaccine within 30 days before the first dose of study intervention
* Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention
* Has had an allogeneic tissue/solid organ transplant
* Has a known psychiatric or substance abuse disorder that would interfere with requirements of the study
* Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula
* Has radiographic evidence of encasement of invasion of a major blood vessel, or of intratumoral cavitation
* Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study intervention
* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
* Has urine protein ≥1 g/24-hour.
* Has presence of gastrointestinal condition including malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib

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Where can I participate?

Cedars-Sinai Cancer at The Angeles Clinic and Research Institute : Saba Mukarram

More about this Clinical Trial

What is the full name of this clinical trial?

MK-3475-U02-01: A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants with Melanoma: Master

Study Details

Disease Type/Condition

Melanoma, Soft Tissue

Principal Investigator

Hamid, Omid

Co-Investigators

Ani Balmanoukian, Cathie T Chung, Inderjit Mehmi, Iryna Singh, Justin Moyers, Kristopher Wentzel, Mark Faries, Navid Hafez

Age Group

Adult

Phase

I/II

IRB Number

STUDY00000595

ClinicalTrials.gov ID

NCT04305054

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Saba Mukarram

Phone

+1 310-231-2181

MukarramS@cshs.org