What is the mechanism of action of this treatment?

The most common treatments for tumors, particularly those involving immune checkpoint inhibitors like pembrolizumab, focus on reactivating the immune system to target cancer cells. Pembrolizumab blocks the PD-1 pathway, which tumors use to hide from immune detection. By inhibiting this pathway, T-cells are reactivated to recognize and destroy cancer cells. This mechanism is significant for tumor patients as it provides a targeted approach to enhance the body's natural defenses against cancer, potentially improving treatment efficacy and patient outcomes.

What side effects are associated with this type of intervention?

Common side effects of treatments similar to MK-0482 and pembrolizumab, which include checkpoint inhibitors and chemotherapy, can vary. Checkpoint inhibitors like pembrolizumab often cause immune-related adverse events such as colitis, hepatitis, pneumonitis, endocrinopathies, and skin reactions. These side effects occur because the immune system can attack normal tissues. Chemotherapy, often used in combination, can cause nausea, vomiting, hair loss, fatigue, and increased risk of infections due to bone marrow suppression. It is important to discuss these potential side effects with a healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors for the treatment of various tumors. Pembrolizumab (Keytruda), an anti-PD-1 monoclonal antibody, is approved for multiple cancers, including non-small cell lung cancer (NSCLC) and melanoma. Nivolumab (Opdivo), another anti-PD-1 therapy, is also approved for similar indications. Additionally, ipilimumab (Yervoy), an anti-CTLA-4 antibody, is often used in combination with nivolumab for enhanced efficacy in melanoma. These approvals highlight the effectiveness of targeting immune checkpoints in cancer therapy, similar to the investigational approach of combining MK-0482 with pembrolizumab.

What other types of research exist?

Promising novel alternatives to MK-0482 for tumor patients considering treatment in 2024 include: 1) Epacadostat in combination with pembrolizumab, which has been studied in metastatic melanoma (ECHO-301/KEYNOTE-252). 2) Pembrolizumab plus lenvatinib, which has received FDA accelerated approval for advanced endometrial carcinoma. 3) Investigational drugs with single-agent activity in multiple myeloma, such as Isatuximab, marizomib, and venetoclax, which may have potential in solid tumors. 4) Pembrolizumab monotherapy or in combination with other agents, as it has shown efficacy in various cancers including non-small cell lung cancer, gastric cancer, and renal cell carcinoma.

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MK-0482 + Pembrolizumab for Advanced Cancer

Phase 1

Waitlist Available

Research Sponsored by Merck Sharp & Dohme Corp.

Eligibility Criteria Checklist

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

Must have

Part 2 Cohort C only: Has histologically confirmed diagnosis of metastatic PDAC and has received no prior systemic therapy for metastatic pancreatic ductal adenocarcinoma (PDAC) including chemotherapy, biological or targeted therapy and has albumin ≥3.0 g/dL

Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Must not have

Part 2 Cohort A only: 1) Has a history of class II-IV congestive heart failure or myocardial infarction within 6 months of start of study treatment 2) Has a known sensitivity to any component of paclitaxel or any of its excipients and 3) Is receiving any medication prohibited in combination with paclitaxel unless medication was stopped within 7 days before the start of study treatment

Has an active infection requiring systemic therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 27 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug, MK-0482, alone and with pembrolizumab, in patients with advanced cancers who have no other treatment options. MK-0482's safety and effectiveness are being evaluated, while pembrolizumab helps the immune system fight cancer. Pembrolizumab has been widely studied and used in various cancers, showing effectiveness and safety in combination with other treatments.

Who is the study for?

This trial is for adults with advanced solid tumors and no remaining treatment options. Specific groups include those with certain types of brain cancer, pancreatic cancer, soft tissue sarcoma, lung cancer, or triple negative breast cancer. Participants must have measurable disease, provide a tumor sample, meet organ function criteria and performance status requirements. Women of childbearing potential must use effective contraception.

What is being tested?

The study tests MK-0482 alone and combined with pembrolizumab in two parts: dose escalation to find the safest dose (Part 1), followed by expansion cohorts to assess safety and effectiveness in specific cancers when combined with pembrolizumab and chemotherapy (Part 2).

What are the potential side effects?

Possible side effects include reactions at the infusion site, fatigue, nausea, immune-related issues such as inflammation in various organs which can be serious. Each patient's experience may vary.

Eligibility Criteria

Inclusion Criteria

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

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I have metastatic pancreatic cancer, haven't had treatment for it, and my albumin level is at least 3.0 g/dL.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I have HIV and it is well controlled with medication.

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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My cancer has spread to my brain or the membranes around my brain.

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I am HIV-positive and have had Kaposi's sarcoma or Multicentric Castleman's Disease.

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I have an autoimmune disease treated with medication in the last 2 years.

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1) You have had heart failure, stroke, unstable angina, or heart attack within the past 6 months. 2) You have noticeable fluid buildup in your abdomen causing discomfort. 3) You are allergic to nab-paclitaxel or gemcitabine, or any of the ingredients they contain.

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I have a history of lung scarring or fibrosis.

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I stopped immunotherapy due to a severe side effect.

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I have had or currently have lung inflammation treated with steroids.

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I have had a transplant from another person in the last 5 years or have signs of my body rejecting the transplant.

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I have an immune system disorder or have been on steroids or other immune-weakening medicines recently.

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I had another cancer but was treated successfully and have been cancer-free for 2 years.

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I've had a severe allergic reaction to specific cancer treatments before.

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

Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Part 1 only)

Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Part 2 only)

+1 more

Secondary study objectives

AUC of MK-0482 When Administered in Combination with Pembrolizumab (Part 1 only)

Area Under the Concentration-Time Curve (AUC) of MK-0482 When Administered as Monotherapy (Part 1 only)

Cmax of MK-0482 When Administered in Combination with Pembrolizumab (Part 1 only)

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

7Treatment groups

Experimental Treatment

Group I: Part 2: Cohort EExperimental Treatment4 Interventions

Participants with metastatic non-squamous non-small cell lung carcinoma (NSCLC) (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion plus Pemetrexed 500 mg/m\^2 via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years) plus carboplatin with desired dose of area under the curve (AUC) 5 and pemetrexed 500 mg/m\^2, both administered via IV infusion, followed by maintenance therapy with pemetrexed 500 mg/m\^2 via IV infusion for up to a total of 35 administrations (up to approximately 2 years).

Group II: Part 2: Cohort DExperimental Treatment2 Interventions

Participants with metastatic soft tissue sarcoma (STS) (2L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years).

Group III: Part 2: Cohort CExperimental Treatment4 Interventions

Participants with metastatic pancreatic ductal adenocarcinoma (PDAC) (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years), Nab-Paclitaxel 125 mg/m\^2 via IV infusion and gemcitabine 1000 mg/m\^2 via IV infusion until PD or unacceptable toxicity that requires discontinuation.

Group IV: Part 2: Cohort BExperimental Treatment2 Interventions

Participants with recurrent non-operable glioblastoma (GBM) current treatment of second line (2L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years).

Group V: Part 2: Cohort AExperimental Treatment3 Interventions

Participants with metastatic triple negative breast cancer (TNBC) first line treatment (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years) and paclitaxel 90 mg/m\^2 via IV infusion until PD or discontinuation.

Group VI: Part 1: MK-0482 MonotherapyExperimental Treatment1 Intervention

Participants receive escalating doses of MK-0482 via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years).

Group VII: Part 1: MK-0482 + Pembrolizumab Combination TherapyExperimental Treatment2 Interventions

Participants receive escalating doses of MK-0482 via IV infusion + pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Paclitaxel

2011

Completed Phase 4

~5450

Carboplatin

2014

Completed Phase 3

~6120

pembrolizumab

2017

Completed Phase 3

~5890

Nab-paclitaxel

2014

Completed Phase 3

~1950

Gemcitabine

2017

Completed Phase 3

~1920

Pemetrexed

2014

Completed Phase 3

~5550

0 / 16Eligibility 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

The most common treatments for tumors, particularly those involving immune checkpoint inhibitors like pembrolizumab, focus on reactivating the immune system to target cancer cells. Pembrolizumab blocks the PD-1 pathway, which tumors use to hide from immune detection. By inhibiting this pathway, T-cells are reactivated to recognize and destroy cancer cells. This mechanism is significant for tumor patients as it provides a targeted approach to enhance the body's natural defenses against cancer, potentially improving treatment efficacy and patient outcomes.

Recurrent glioma clinical trial, CheckMate-143: the game is not over yet.Understanding Immune Checkpoint Inhibitors for Effective Patient Care.The State of Immune Checkpoint Inhibition in Urothelial Carcinoma: Current Evidence and Future Areas of Exploration.