MK-4464 + Pembrolizumab for Advanced Cancer

No longer recruiting at 7 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

Disqualifiers: CNS metastases, Active infection, 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 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the new drug MK-4464, an experimental treatment, is safe and effective for people with advanced solid tumors, either alone or with pembrolizumab (also known as KEYTRUDA, an immunotherapy). Participants will receive different combinations of these drugs through an IV infusion every three weeks. The trial targets individuals with advanced cancer that hasn't responded to other treatments and who are willing to provide a tumor sample for analysis. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have had chemotherapy, radiation, or biological cancer therapy within 4 weeks before starting the study. It's best to discuss your specific medications with the trial team.

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

Research is examining the safety of MK-4464 both alone and in combination with pembrolizumab. Although specific safety data for the combination is not yet available, pembrolizumab has received approval for treating several cancer types, indicating its general safety.

Studies are investigating how MK-4464 aids the immune system in attacking cancer cells. As this research remains in the early stages, the primary goal is to assess the drug's safety in humans, with careful monitoring for any side effects.

Zirconium-89 is primarily used for imaging, allowing researchers to observe how the drugs function within the body.

Since the study is in an early phase, the main focus is understanding the safety of MK-4464. The trials aim to determine the safest dose levels and closely monitor any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine MK-4464 with pembrolizumab, potentially enhancing the immune system's ability to attack cancer cells. Unlike traditional treatments that might target cancer cells directly, pembrolizumab is a type of immunotherapy that blocks a protein called PD-1, helping the immune system recognize and destroy cancer cells. MK-4464, when used alongside pembrolizumab, might further boost this immune response. Additionally, the use of Zirconium 89 (89Zr)-MK-4464 in one of the treatment arms allows researchers to track the distribution of MK-4464 in the body, offering insights into how the treatment interacts with the cancer and potentially improving its efficacy.

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

Research has shown that pembrolizumab effectively treats advanced cancers, such as non-small cell lung cancer, by extending patient survival and slowing disease progression. One study found that pembrolizumab benefited 45.8% of patients with advanced cancers. In this trial, some participants will receive MK-4464, a new treatment that aids the immune system in attacking tumors and killing cancer cells. Although human studies on MK-4464 remain limited, it shows promise in directly targeting cancer cells. Other participants will receive MK-4464 combined with pembrolizumab, potentially enhancing the immune system's cancer-fighting ability. These findings suggest a potentially effective treatment approach for advanced cancers. ^{1 2 3 6 7}

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 solid tumors who've tried, can't tolerate, or refused all other treatments. They must have a good performance status (0-1 on the ECOG scale), controlled HIV or hepatitis B if present, and provide a tumor sample. Excluded are those with recent cancer therapies, active CNS metastases, infections needing treatment, lung disease requiring steroids, autoimmune diseases treated in the last 2 years, major surgery effects not recovered from, live vaccines taken within 30 days before starting the study intervention.

Inclusion Criteria

Must submit a baseline tumor sample for analysis

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

I have HIV and it is well controlled with medication.

Exclusion Criteria

I have had a stem cell or organ transplant.

Has known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the study

Is currently participating and receiving study intervention in a study of an investigational agent or has participated and received study intervention in a study of an investigational agent or has used an investigational device within 28 days

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MK-4464 as monotherapy or in combination with pembrolizumab every 3 weeks for up to 35 cycles

Up to 24 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• MK-4464
• Pembrolizumab

Trial Overview The study tests MK-4464 alone and combined with Pembrolizumab to evaluate safety and early effectiveness in treating advanced solid tumors. It also looks at how the body processes these drugs (pharmacokinetics). Participants will be randomly assigned to receive either MK-4464 by itself or alongside Pembrolizumab.

How Is the Trial Designed?

Group I: MK-4464 + Pembrolizumab + Zirconium 89 (89Zr)-MK-4464 Experimental Treatment 3 Interventions

Participants will receive an IV infusion of 89Zr-MK-4464 + IV infusion of MK-4464 on Cycle 1 Day 1, followed by an IV infusion of MK-4464 + a 200 mg IV infusion of pembrolizumab starting on Cycle 2 Day 1 and every 3 weeks for up to 35 cycles. Each cycle=3 weeks. MK-4464 doses will be based on safety of MK-4464 monotherapy arm. Participants may receive a 200 mg IV infusion of pembrolizumab on cycle 36.

Group II: MK-4464 + Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive an IV infusion of MK-4464 administered in escalating doses and a 200 mg IV infusion of Pembrolizumab every 3 weeks for up to 35 cycles. Escalation to subsequent MK-4464 doses will be based on safety of MK-4464 monotherapy arm.

Group III: MK-4464 Experimental Treatment 1 Intervention

Participants will receive an intravenous (IV) infusion of MK-4464 administered in escalating doses every 3 weeks for up to 35 cycles. Escalation to subsequent MK-4464 doses will be based on safety of previous dose.

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 (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]

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]

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]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

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]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

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. withpower.com withpower.com/trial/phase-1-advancedmetastatic-solid-tumors-9-2022-e763b

MK-4464 + Pembrolizumab for Advanced Cancer 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12454464/

Real-World Outcomes of Pembrolizumab in Advanced ... Among 4127 patients, the median overall survival was 816 days. Mortality was higher in patients aged 65–84 years (adjusted hazards ratio 1.39, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05514444

NCT05514444 | Study of MK-4464 as Monotherapy and in ... The purpose of this study is to assess the safety, pharmacokinetics, and preliminary efficacy of MK-4464 as monotherapy and in combination with ...

4. onderzoekmetmensen.nl onderzoekmetmensen.nl/en/node/53771/pdf

A Phase 1, Open-label, Multicenter Study MK4464 recruits immune cells into tumors and directly activates killing of cancer cells. MK4464 binds to CEACAM5 (on cancer cells) and NKG2D and ...

5. msdclinicaltrials.com msdclinicaltrials.com/trial/nct05514444/

Study of MK-4464 as Monotherapy and in Combination With ... The purpose of this study is to assess the safety, pharmacokinetics, and preliminary efficacy of MK-4464 as monotherapy and in combination with pembrolizumab

6. ctv.veeva.com ctv.veeva.com/study/study-of-mk-4464-as-monotherapy-and-in-combination-with-pembrolizumab-in-participants-with-advanced

Study of MK-4464 as Monotherapy and in Combination With ... The purpose of this study is to assess the safety, pharmacokinetics, and preliminary efficacy of MK-4464 as monotherapy and in combination with pembrolizumab

7. trialstransparency.merckclinicaltrials.com trialstransparency.merckclinicaltrials.com/Upload/897_D1_PPLS_2023-504855-28_for%20pub_not%20r_05Jul2023_V1.0_MK-4464-001-04.pdf

A clinical study of MK-4464 to treat people with advanced ... MK-4464 is a study medicine designed to treat advanced solid tumors. The goal of this study is to learn about: • The safety of MK-4464 and how ...