What is the mechanism of action of this treatment?

Immune checkpoint inhibitors, such as those targeting ILT4, PD-1, and CTLA-4, work by blocking proteins that inhibit the immune system's ability to attack cancer cells. By preventing these inhibitory signals, these treatments enhance the immune response against tumors. This mechanism is significant for tumor patients as it leverages the body's natural defenses to fight cancer more effectively, potentially improving outcomes and reducing side effects compared to conventional therapies.

What side effects are associated with this type of intervention?

Common side effects of immune checkpoint inhibitors, such as pembrolizumab, nivolumab, and ipilimumab, include fatigue, rash, pruritus, diarrhea, and colitis. More severe immune-related adverse events can occur, such as pneumonitis, hepatitis, endocrinopathies (e.g., hypothyroidism, adrenal insufficiency), and nephritis. These treatments can also lead to immune-related adverse events requiring systemic immunosuppression, which may impact survival and time to treatment failure. It is important for patients to be closely monitored for these side effects during treatment.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors for the treatment of various tumors. Notable examples include pembrolizumab (Keytruda) and nivolumab (Opdivo), both of which target PD-1 and are approved for multiple cancers, including melanoma and non-small cell lung cancer. Atezolizumab (Tecentriq) targets PD-L1 and is approved for urothelial carcinoma and non-small cell lung cancer. Ipilimumab (Yervoy), targeting CTLA-4, is approved for melanoma. These drugs work by enhancing the immune system's ability to fight cancer, similar to the investigational drug MK-4830, which targets ILT4.

What other types of research exist?

Promising novel alternatives to MK-4830 for tumor patients include: 1) Nivolumab plus relatlimab, which has shown efficacy in metastatic melanoma. 2) Pembrolizumab combined with chemotherapy, as seen in various studies for non-small-cell lung cancer. 3) Cemiplimab plus chemotherapy, which has demonstrated positive outcomes in non-small-cell lung cancer. 4) Durvalumab with or without tremelimumab in combination with chemotherapy, as explored in the POSEIDON study for non-small-cell lung cancer.

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Other

MK-4830 + Pembrolizumab for Cancer

Phase 1

Waitlist Available

Research Sponsored by Merck Sharp & Dohme LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Expansion phase Arm C participants: Has histologically confirmed recurrent or metastatic head and neck squamous cell cancer (HNSCC) of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies, Has experienced disease progression at any time during or after treatment with a platinum-containing (eg, carboplatin or cisplatin) regimen with or without cetuximab

Expansion phase Arm D participants: Has histologically confirmed advanced or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies, Has not had any prior programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) therapy

Must not have

Expansion phase Arm H participants: Has received prior systemic anticancer therapy for advanced RCC with a tyrosine kinase inhibitor, Has a clinically significant gastrointestinal (GI) abnormality, Has a history of untreated deep vein thrombosis or pulmonary embolism within 6 months prior to screening, Has poorly controlled hypertension, Has active GI bleeding, Has evidence of inadequate wound healing, Has active bleeding disorder or other history of significant bleeding episodes within 30 days prior to randomization, Has hemoptysis within 6 weeks prior to randomization, Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation

Has an active infection requiring therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 27 months

Awards & highlights

Summary

This trial is testing a new drug called MK-4830 alone and with other cancer treatments to see if it is safe and effective. It focuses on cancer patients, including those in China. The treatments work by helping the immune system fight cancer and killing cancer cells.

Who is the study for?

This trial is for adults with various advanced solid tumors, including specific types such as pancreatic adenocarcinoma, renal cell cancer, and non-small-cell lung cancer. Participants must have tried certain treatments without success or be ineligible for them. They should have measurable disease, adequate organ function, and agree to contraception if applicable.

What is being tested?

The study tests MK-4830 alone and combined with Pembrolizumab in treating advanced tumors. It includes dose escalation to assess safety and preliminary efficacy; dose expansion to evaluate response rates; plus a coformulation part testing a mix of MK-4830 and Pembrolizumab.

What are the potential side effects?

Possible side effects include reactions at the infusion site, fatigue, changes in blood counts leading to increased infection risk or bleeding problems, potential liver or kidney issues due to organ inflammation, allergic reactions, and other immune-related adverse events.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer in the head or neck area has returned or spread and didn't respond to platinum-based treatment.

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My cancer is in the mouth or throat and can't be cured with surgery or radiation, and I haven't had PD-1/PD-L1 therapy.

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I have advanced non-squamous NSCLC and haven't had systemic therapy for it.

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My mesothelioma has returned or spread and cannot be cured with standard treatments, but I can receive chemotherapy.

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I have metastatic pancreatic cancer and received 1-3 prior treatments.

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My cancer is a type of pancreatic cancer that has spread.

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I have advanced or recurrent kidney cancer with clear cells and haven't had systemic therapy for it.

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I have had 1 to 3 treatments for my condition.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am currently being treated for an infection.

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I have serious heart problems, including recent heart attacks or severe heart failure.

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I have had lung inflammation treated with steroids or have it now.

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I have or had lung disease that affects the tissue and space around the air sacs.

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I have an autoimmune disease but haven't needed systemic treatment in the last 2 years, except for vitiligo or childhood asthma.

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My cancer does not have a high MSI status.

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I still have side effects from radiation that are not mild and I need steroids for lung inflammation.

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I have recovered from major surgery and have no infections.

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I have had more than 3 treatments for advanced pancreatic cancer.

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I have lost more than 10% of my weight in the last 2 months, have fluid in my abdomen, and cancer has spread to the lining of my abdomen.

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I have symptoms like cough or chest pain due to fluid in my chest and have had a transplant.

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My tumor is in the brainstem or spinal cord, is larger than 6 cm, or needs steroids.

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I have had chemotherapy or targeted therapy for Stage IIIb/IV non-squamous NSCLC and treatment with anti-PD-1, PD-L1, or PD-L2.

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I stopped immunotherapy due to severe side effects.

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I have been taking more than 10 mg of steroids daily in the last week.

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I've had a severe allergic reaction to monoclonal antibody treatment or am allergic to pembrolizumab or its chemotherapy components.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 27 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 27 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 27 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose-Limiting Toxicities (DLTs)

Number of Participants Who Discontinued Study Treatment Due to an AE

Number of Participants Who Experienced an Adverse Event (AE)

+2 more

Secondary study objectives

Area Under the Curve (AUC) of Plasma MK-4830

Maximum Drug Concentration (Cmax) of Plasma MK-4830

Maximum Drug Concentration (Cmax) of Plasma Pembrolizumab in Arm M

+3 more

Trial Design

17Treatment groups

Experimental Treatment

Group I: Dose Expansion, Arm M: Advanced Solid Tumor in Chinese Participants In ChinaExperimental Treatment2 Interventions

Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in Chinese participants, who reside in China, have histologically or cytologically-confirmed advanced/metastatic solid tumor, and who have been previously treated with at least 2 prior lines of therapy. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Group II: Dose Expansion, Arm L: MesotheliomaExperimental Treatment4 Interventions

Triple combination therapy with pembrolizumab plus preliminary RP2D A of MK-4830 plus pemetrexed plus cisplatin in participants who have histologically confirmed advanced mesothelioma. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1 for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Pemetrexed will be administered by IV, on Day 1 of each Q3W cycle for a maximum of 6 cycles. Each cycle is 21 days. Cisplatin will be administered by IV, on Day 1 of each Q3W cycle for a maximum of 6 cycles. Each cycle is 21 days.

Group III: Dose Expansion, Arm K: Triple negative Breast Cancer (TNBC)Experimental Treatment3 Interventions

Triple combination therapy with pembrolizumab plus preliminary RP2D A of MK-4830 plus paclitaxel in participants who have histologically confirmed TNBC. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1 for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Paclitaxel will be administered by IV on Days 1, 8, and 15 every 4 weeks (Q4W) until disease progression or prohibitive toxicity.

Group IV: Dose Expansion, Arm J: Ovarian CancerExperimental Treatment3 Interventions

Triple combination therapy with pembrolizumab plus preliminary RP2D A of MK-4830 plus paclitaxel in participants who have histologically confirmed, ovarian cancer. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1 for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Paclitaxel will be administered by IV, once every week (QW) on Days 1, 8, and 15 of each 21-day cycle until disease progression or prohibitive toxicity.

Group V: Dose Expansion, Arm I: R/M Gastric/GE Junction AdenocarcinomaExperimental Treatment2 Interventions

Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants who have histologically or cytologically-confirmed recurrent or metastatic (R/M) gastric or gastroesophageal (GE) junction adenocarcinoma and who have been previously treated with at least 2 prior lines of therapy. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Group VI: Dose Expansion, Arm H: RCC, +LenvatinibExperimental Treatment3 Interventions

Combination therapy with the preliminary RP2D A of MK-4830, pembrolizumab, and lenvatinib in participants with advanced renal cell carcinoma (RCC). MK-4830 will be administered IV, Q3W, starting with Cycle 1 following pembrolizumab infusion, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years). Lenvatinib will be administered orally once daily for up to 35 cycles of 21 days (up to approximately 2 years).

Group VII: Dose Expansion, Arm G: NSCLC, +Carboplatin/PemetrexedExperimental Treatment4 Interventions

Combination therapy with the preliminary RP2D A of MK-4830, pembrolizumab, and carboplatin/pemetrexed in participants with advanced non-squamous non-small-cell-lung-cancer (NSCLC) (Stage IIIB or IV). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles. Carboplatin and pemetrexed will be administered IV Q3W, starting with Cycle 1, Day 1, for 4 cycles, followed by pemetrexed Q3W continuous with MK-4830 and pembrolizumab, up to 35 cycles. Each cycle is 21 days (up to approximately 2 years).

Group VIII: Dose Expansion, Arm F: First-Line Advanced NSCLC, Dose BExperimental Treatment2 Interventions

Combination therapy with the preliminary RP2D B of MK-4830, and pembrolizumab, in participants who have histologically-confirmed, first-line treatment advanced non-small-cell-lung-cancer (NSCLC) (Stage IIIB or IV). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Group IX: Dose Expansion, Arm E: First-Line Advanced NSCLC, Dose AExperimental Treatment2 Interventions

Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants who have histologically-confirmed, first-line treatment advanced non-small-cell-lung-cancer (NSCLC) (Stage IIIB or IV). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Group X: Dose Expansion, Arm D: PD-L1 positive HNSCC, Dose AExperimental Treatment2 Interventions

Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants who have histologically or cytologically-confirmed advanced programmed death-ligand 1 (PD-L1) positive head and neck squamous cell carcinoma (HNSCC). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Group XI: Dose Expansion, Arm C: R/M HNSCCExperimental Treatment2 Interventions

Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants who have histologically or cytologically-confirmed recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) whose disease progressed on an anti-programmed cell death 1/programmed cell death ligand 1 (PD1/L1) therapy. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Group XII: Dose Expansion, Arm B: Glioblastoma (GBM)Experimental Treatment2 Interventions

Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants with histologically or cytologically confirmed GBM. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Group XIII: Dose Expansion, Arm A: Pancreatic AdenocarcinomaExperimental Treatment2 Interventions

Combination therapy with the preliminary recommended phase 2 dose (RP2D) A of MK-4830, and pembrolizumab, in participants with histologically or cytologically confirmed pancreatic adenocarcinoma. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Group XIV: Dose Escalation, Part C: MK-4830 and PembrolizumabExperimental Treatment2 Interventions

Combination therapy with MK-4830 and pembrolizumab (with MK-4830 doses determined by an mTPI design). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Group XV: Dose Escalation, Part B: MK-4830 MonotherapyExperimental Treatment1 Intervention

MK-4830 monotherapy (with MK 4830 doses determined by a modified toxicity probability interval \[mTPI\] method) will be administered IV, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Participants enroll with histologically or cytologically confirmed pleural or peritoneal malignant mesothelioma, epithelial, sarcomatoid, or biphasic subtypes.

Group XVI: Dose Escalation, Part A: MK-4830 MonotherapyExperimental Treatment1 Intervention

MK-4830 monotherapy (with MK-4830 doses determined by an accelerated titration design \[ATD\]) will be administered intravenously (IV), every 3 weeks (Q3W), starting with Cycle 1, Day 1, for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Participants enroll with histologically or cytologically confirmed pancreatic adenocarcinoma.

Group XVII: Coformulation Phase, Arm N: MK-4830A (Coformulation of MK-4830 + pembrolizumab)Experimental Treatment1 Intervention

Monotherapy with MK-4830A, a coformulation of MK-4830 800 mg + pembrolizumab 200 mg, in participants with histologically or cytologically-confirmed advanced/metastatic solid tumor, and who and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit. MK-4830A will be administered IV, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Paclitaxel

2011

Completed Phase 4

~5810

Cisplatin

2013

Completed Phase 3

~2360

Pembrolizumab

2017

Completed Phase 2

~2070

Carboplatin

2014

Completed Phase 3

~6120

Lenvatinib

2017

Completed Phase 4

~2040

Pemetrexed

2014

Completed Phase 3

~5550

0 / 25Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Immune checkpoint inhibitors, such as those targeting ILT4, PD-1, and CTLA-4, work by blocking proteins that inhibit the immune system's ability to attack cancer cells. By preventing these inhibitory signals, these treatments enhance the immune response against tumors. This mechanism is significant for tumor patients as it leverages the body's natural defenses to fight cancer more effectively, potentially improving outcomes and reducing side effects compared to conventional therapies.

Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.