NGM831 + Pembrolizumab for Cancer

Not currently recruiting at 16 trial locations

Overseen By NGM Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: NGM Biopharmaceuticals, Inc

Must not be taking: ILT3, LAIR1

Disqualifiers: Others

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

Compensation: Varies

Number of Visits: 1

Duration: 9 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new drug, NGM831, both alone and in combination with pembrolizumab, a common cancer treatment, in individuals with advanced or metastatic solid tumors. Researchers aim to determine the optimal dose and explore how these drugs might work together to combat cancer. Participants should have advanced or metastatic solid tumor cancer and be in good health to tolerate the treatment. This trial may suit individuals who have not previously received treatments targeting specific proteins, such as ILT3 or LAIR1, in their cancer therapy. As a Phase 1 trial, this research focuses on understanding the treatment's effects in humans, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that NGM831, whether used alone or with pembrolizumab or pembrolizumab plus NGM438, has generally been safe. About 33% of patients experienced moderate side effects, but no deaths were linked to the treatment, suggesting it is generally well-tolerated. Pembrolizumab, a common cancer treatment already approved by the FDA, is widely used, adding confidence about its safety in combination with other treatments. However, as this is an early-stage study, more research is needed to fully understand the safety of these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NGM831 in combination with pembrolizumab because this treatment offers a novel approach to fighting cancer. Unlike standard therapies that primarily focus on inhibiting cancer cell growth, NGM831 is designed to enhance the body's immune response against tumors. By pairing it with pembrolizumab, an established immune checkpoint inhibitor, there's potential to boost the treatment's effectiveness, offering new hope for patients. Additionally, the trial explores NGM831 both as a single agent and in combination with NGM438, which could unveil even more robust strategies to combat various cancers. This innovative angle is what sets these treatments apart from existing options.

What evidence suggests that this trial's treatments could be effective for advanced or metastatic solid tumors?

Research has shown that NGM831 is designed to block ILT3, a molecule that can weaken the immune system's response. This might help the immune system attack cancer cells more effectively. Studies have generally found NGM831 to be safe and well-tolerated. In this trial, some participants will receive NGM831 as a monotherapy, while others will receive it in combination with pembrolizumab. Pembrolizumab, often used with NGM831, has improved survival rates in cancers like non-small cell lung cancer and melanoma by helping the immune system recognize and fight cancer better. Early findings suggest that using NGM831 with pembrolizumab might boost these effects, potentially offering a new way to treat advanced or spreading solid tumors. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors, including various cancers like lung, breast, and colorectal cancer. Participants should be in good physical condition (performance status of 0 or 1) and have recovered from previous treatments' acute effects. They must also have adequate bone marrow, kidney, and liver function. Those who've had prior treatment targeting ILT3 cannot join.

Inclusion Criteria

My bone marrow, kidney, and liver are functioning well.

My cancer is advanced or has spread and was confirmed by a lab test.

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

Exclusion Criteria

I have received treatments targeting ILT3 before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NGM831 as monotherapy or in combination with pembrolizumab and NGM438

9 weeks

Cycle 1 and Cycle 3 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• NGM831
• Pembrolizumab

Trial Overview The study is testing NGM831 on its own and combined with pembrolizumab to see how well they work against different types of advanced cancers. The goal is to find out if these treatments can help control the growth of cancer cells.

How Is the Trial Designed?

Group I: NGM831 combination dose finding with pembrolizumab (KEYTRUDA®) Experimental Treatment 1 Intervention

Part 1b NGM831 plus pembrolizumab (KEYTRUDA®)

Group II: NGM831 and NGM438 Combination Dose Finding with pembrolizumab (KEYTRUDA®) Experimental Treatment 1 Intervention

Part 1c NGM831 and NGM438 plus pembrolizumab (KEYTRUDA®)

Group III: NGM831 Monotherapy Dose Escalation Experimental Treatment 1 Intervention

Part 1a Single Agent Dose Escalation

Who Is Running the Clinical Trial?

NGM Biopharmaceuticals, Inc

Lead Sponsor

Trials

25

Recruited

2,500+

Merck Sharp & Dohme LLC

Industry 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 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 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]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

Pembrolizumab (PEM) significantly improved short-term treatment effectiveness and long-term survival rates in patients with advanced cutaneous malignant melanoma compared to chemotherapy with Temozolomide, with a notable increase in one-year survival rates (53.85% vs. 40.00%).

The use of PEM did not lead to a higher incidence of adverse reactions compared to the control group, indicating that it is a relatively safe treatment option for patients with this type of melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. Fu, L., Zhang, H., Jiang, J., et al.[2021]

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 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]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

In a study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab and pemetrexed-carboplatin (PC) significantly improved the objective response rate (56.7% vs. 30.2% with PC alone) and progression-free survival (PFS) compared to PC alone, with a hazard ratio (HR) of 0.53.

The updated analysis showed a favorable overall survival (OS) hazard ratio of 0.56 for the pembrolizumab plus PC group, indicating a significant survival benefit, although 41% of patients experienced grade 3 to 5 treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer. Borghaei, H., Langer, CJ., Gadgeel, S., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05215574

NCT05215574 | Study of NGM831 as Monotherapy and in ... Study of NGM831 as Monotherapy and in Combination with Pembrolizumab or Pembrolizumab and NGM438 in Advanced or Metastatic Solid Tumors

2. aacrjournals.org aacrjournals.org/cancerres/article/82/12_Supplement/LB216/704680/Abstract-LB216-Pre-clinical-characterization-of

Pre-clinical characterization of NGM831, an ILT3 antagonist ... These data support the clinical development of the ILT3 antagonist antibody NGM831 alone and in combination with immune checkpoint blockade.

3. synapse.patsnap.com synapse.patsnap.com/drug/dd8c5f8003b5418285ddf91ac0ecdefd

NGM-831 - Drug Targets, Indications, Patents NGM831 and NGM438, alone and in combination with pembrolizumab, have been generally well-tolerated and there have been no dose limiting toxicities noted to date ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12025738/

An Update on Completed and Ongoing Clinical Trials Pancreatic cancer remains one of the most lethal malignancies, with a 5-year relative survival rate of 12.8% [1]. In 2024, it was estimated that 66,440 new ...

5. biospace.com biospace.com/ngm-bio-announces-initiation-of-phase-1-1b-clinical-trial-of-ngm831-for-the-treatment-of-patients-with-advanced-solid-tumors

NGM Bio Announces Initiation of Phase 1/1b Clinical Trial ... NGM831 is an antagonist antibody product candidate designed to block the interaction of ILT3 (also known as LILRB4) with fibronectin, a key component of the ...

6. fightcolorectalcancer.org fightcolorectalcancer.org/zh/clinical-trial/nct05215574/

Study of NGM831 as Monotherapy and in Combination ... NGM831 (a ILT3 antagonist) as monotherapy and in combination with pembrolizumab in advanced or metastatic solid tumors (CRC included). Trial starts with NGM831 ...

7. bcan.org bcan.org/clinicaltrials/ngm831-as-monotherapy-and-in-combination-with-pembrolizumab-in-advanced-or-metastatic-solid-tumors/

NGM831 as Monotherapy and in Combination With ... PRIMARY OUTCOMES. Primary Outcome 1 - Measure: Number of Patients with Dose-limiting Toxicities ; ELIGIBILITY · Gender: All ; OFFICIAL INFORMATION. Name: N/A.

8. withpower.com withpower.com/trial/phase-1-cholangiocarcinoma-2-2022-fb698

NGM831 + Pembrolizumab for Cancer · Info for Participants The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that ...

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Study of NGM831 as Monotherapy and in Combination With ... Search Results. Study of NGM831 as Monotherapy and in Combination With Pembrolizumab or Pembrolizumab and NGM438 in Advanced or Metastatic Solid Tumors.