MK-0472 + Pembrolizumab for Advanced Cancer

Recruiting at 33 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Antiretrovirals, HBV antivirals

Must not be taking: Proton-pump inhibitors, H2 blockers

Disqualifiers: Second malignancy, Hypercalcemia, Glaucoma, Cardiovascular disease, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: Up to approximately 56 months

178 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, MK-0472 (an experimental treatment), both alone and with other drugs like pembrolizumab (also known as KEYTRUDA), for individuals with advanced or metastatic solid tumors. Researchers aim to assess the effectiveness and safety of these treatments. Participants must have a confirmed diagnosis of advanced cancer, such as lung, kidney, or breast cancer, and have tried other treatments without success. This study could offer new hope for managing difficult-to-treat cancers. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have taken a proton-pump inhibitor or H2 blocker within 7 days before starting the trial, and you must not be on chronic systemic steroid therapy or other immunosuppressive treatments within 7 days prior to the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pembrolizumab, also known as KEYTRUDA, is generally safe for treating various types of cancer. However, some patients may experience side effects such as tiredness and nausea. Discussing any concerns with a doctor is important.

In contrast, MK-0472 is still under investigation, and limited information is available about its safety. This phase 1 trial primarily aims to assess the safety of MK-0472 and its tolerability. Researchers remain hopeful but continue to learn about potential side effects.

For those considering participation in a trial with these treatments, discussing it with a doctor is advisable. They can provide insights into the potential benefits and risks based on the latest information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they bring new approaches to tackling advanced cancer. MK-0472 is an innovative oral capsule treatment, potentially offering a more convenient delivery method compared to traditional intravenous chemotherapy. When combined with pembrolizumab, an existing immunotherapy drug, MK-0472 might enhance the immune system's ability to fight cancer more effectively. Additionally, the combination with MK-1084 is another promising avenue, as it could provide a synergistic effect in targeting cancer cells. These treatments represent a fresh take compared to conventional options like chemotherapy, which often have more severe side effects and limit patient quality of life.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

Research shows that MK-0472 is undergoing testing in patients with advanced solid tumors. This drug acts as a KRAS inhibitor, targeting a specific change in cancer cells. In other studies of similar drugs, patients with non-small cell lung cancer achieved an 80.6% rate of disease control, with the cancer remaining stable for about 6.8 months.

In this trial, participants may receive MK-0472 alone or with pembrolizumab. Combining MK-0472 with pembrolizumab, already effective in treating advanced cancers like melanoma, shows promise. In some trials, pembrolizumab alone had a 24% response rate. When combined with chemotherapy, it significantly reduced the chance of cancer progression compared to chemotherapy alone. These findings suggest that MK-0472 could be effective on its own and even more so when combined with pembrolizumab. ^{1 2 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors that have alterations in certain genes and who've tried all other treatments. They must not have serious eye conditions, skin disorders, known allergies to the drugs being tested, recent use of certain stomach acid medications, or a history of severe reactions to similar cancer therapies.

Inclusion Criteria

I am hepatitis B positive but have been on antiviral therapy for over 4 weeks with an undetectable viral load.

My advanced cancer has specific genetic changes and I've tried all known beneficial treatments.

I have HIV and have been on stable HIV medication for over 4 weeks.

Exclusion Criteria

I have another cancer that is growing or was treated in the last 2 years.

I have a serious heart condition.

I stopped a cancer treatment due to side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MK-0472 as monotherapy or in combination with pembrolizumab or MK-1084 until disease progression or withdrawal

Up to approximately 56 months

Visits every 3 weeks for up to 35 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MK-0472
• Pembrolizumab

Trial Overview The study tests MK-0472 alone and combined with Pembrolizumab on participants with specific genetic tumor profiles. It aims to evaluate the effectiveness and safety without a primary hypothesis; meaning they're exploring how well these treatments work without trying to prove a specific idea.

How Is the Trial Designed?

Group I: MK-0472 + Pembrolizumab Experimental Treatment 2 Interventions

Participants receive MK-0472 via oral capsule according to one of the protocol-specified dosing regimens until disease progression or withdrawal/discontinuation, plus pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Group II: MK-0472 + MK-1084 Experimental Treatment 2 Interventions

Participants receive MK-0472 via oral capsule according to one of the protocol-specified dosing regimens, plus MK-1084 via oral capsule until disease progression or withdrawal/discontinuation.

Group III: MK-0472 Experimental Treatment 1 Intervention

Participants receive MK-0472 via oral capsule according to one of the protocol-specified dosing regimens until disease progression or withdrawal/discontinuation.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., et al.[2022]

In a phase 1a/b trial involving 26 patients with PD-L1-positive non-small cell lung cancer (NSCLC), the combination of ramucirumab and pembrolizumab showed a manageable safety profile, with 84.6% experiencing treatment-related adverse events, primarily hypertension.

The treatment demonstrated promising efficacy, with an objective response rate of 42.3%, and particularly strong results in patients with high PD-L1 expression (TPS ≥ 50%), who had a median progression-free survival that was not reached.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC. Herbst, RS., Arkenau, HT., Bendell, J., et al.[2023]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05853367

Study of MK-0472 in Participants With Advanced/Metastatic ... The purpose of this study is to assess the efficacy, safety, and tolerability of MK-0472 administered as monotherapy and in combination with pembrolizumab ...

2. withpower.com withpower.com/trial/phase-1-neoplasms-5-2023-a13e8

MK-0472 + Pembrolizumab for Advanced Cancer This trial is testing a new drug called MK-0472, alone and with other drugs, in patients with advanced or spreading solid tumors.

3. sigma.larvol.com sigma.larvol.com/moa.php?e1=1013148&e2=&sourcepg=TZMoa&tab=OTTtrac&sr=now&er=1+month&ipwnd=on&rlink=,tab=OTTtrac,sourcepg=TZMoa,itype=0,1&rflag=1&page=2

KRAS G12C inhib Trials 2022-001088-29: Study of efficacy and safety of JDQ443 single-agent as first-line treatment for patients with locally advanced or metastatic KRAS G12C- mutated ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2405803324002759

KRAS inhibitors: resistance drivers and combinatorial ... Here, 80.6% of patients with NSCLC displayed DC, PFS was 6.8 months, and median overall survival (OS) was 12.5 months [35]. Based on the favorable findings of ...

5. ancora.ai ancora.ai/fr/details/NCT05853367

Study of MK-0472 in Participants With Advanced/Metastatic ... The purpose of this study is to assess the efficacy, safety, and tolerability of MK-0472 administered as monotherapy and in combination with ...

6. centers.louisville.edu centers.louisville.edu/brown-cancer-center/clinical-trials/genitourinary-clinical-trials

Genitourinary Clinical Trials - Centers & Institutes - UofL The purpose of this study is to assess the efficacy, safety, and tolerability of MK-0472 administered as monotherapy and in combination with pembrolizumab (MK- ...

7. humanforschung-schweiz.ch humanforschung-schweiz.ch/de/studiensuche/studien-detail/62989/translate/en/?cHash=6c2aa14fdac84eeb05a5e086f1840538

An open multicenter clinical phase 1/1b study of MK-0472 ... These are the two investigational drugs in the study: - MK-0472: MK-0472 inhibits and blocks the SHP2 protein, which in turn leads to an inhibition of the cell ...

8. etudes-cliniques-oncologie.ch etudes-cliniques-oncologie.ch/etudes/mk-0472-a-phase-1-1b-open-label-multicenter-clinical-study-of-mk-0472-asmonotherapy-and-combination-therapy-in-participants-with-advanced-metastatic-solid-tumors

MK0472-001: A Phase 1/1b Open-label, Multicenter Clinical ... A Phase 1/1b Open-label, Multicenter Clinical Study of MK-0472 asMonotherapy and Combination Therapy in Participants with Advanced/Metastatic Solid Tumors.