NGM438 + Pembrolizumab for Cancer

Not currently recruiting at 5 trial locations

Overseen By NGM Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: NGM Biopharmaceuticals, Inc

Must not be taking: LAIR1 inhibitors

Disqualifiers: Others

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

Compensation: Varies

Number of Visits: 1

Duration: Approximately 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for individuals with advanced or metastatic solid tumors, which are cancers that have spread and do not respond to standard treatments. Researchers are testing NGM438, an experimental drug, both alone and with Pembrolizumab (KEYTRUDA®), a medication that aids the immune system in fighting cancer. The trial aims to determine the optimal dose and understand how these treatments interact. It suits those whose cancer has not improved with existing treatments and who maintain good organ function and physical health. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if 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 NGM438 is a new treatment under study for its potential to fight cancer by targeting a specific protein called LAIR1. It has been tested in labs and early trials, designed to enhance the immune system's ability to fight cancer by blocking collagen, which can weaken immune responses.

Since NGM438 is in the early stages of testing, detailed safety information in humans is still being collected. However, its testing in humans suggests some initial confidence in its safety from earlier studies. Early trials primarily focus on ensuring the treatment's safety and determining the right dose.

Pembrolizumab, also known as Keytruda, is a well-known cancer treatment already approved for many types of cancer. It works by helping the immune system attack cancer cells. Its safety is well-documented, with the most common side effects being tiredness, skin issues, and minor digestive problems.

In this trial, researchers are testing NGM438 both alone and with pembrolizumab. While pembrolizumab's safety is established, the new combination with NGM438 is still under study to understand its tolerance and any new side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NGM438, especially when combined with pembrolizumab (KEYTRUDA®), because it offers a novel approach to cancer treatment. Unlike most standard cancer therapies that often target the cancer cells directly, NGM438 is designed to modulate the tumor microenvironment, potentially enhancing the immune system's ability to fight cancer. This could improve the effectiveness of pembrolizumab, an already widely used checkpoint inhibitor. By working together, these treatments might offer a more potent and durable response against cancer compared to existing options.

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

Research shows that NGM438 is a new treatment designed to block a protein called LAIR1, which can weaken the immune system's ability to fight cancer. Lab studies have demonstrated that NGM438 helps the immune system better target cancer cells. In this trial, some participants will receive NGM438 alone, while others will receive it in combination with pembrolizumab, a well-known cancer treatment. Pembrolizumab has improved survival rates in patients with certain cancers, such as lung cancer. Together, these treatments could offer a promising new approach to treating advanced cancers. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors who have tried all other treatments without success. They should be in good physical condition (able to perform daily activities) and have normal bone marrow, kidney, and liver function. People can't join if they've previously received treatment targeting LAIR1.

Inclusion Criteria

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

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

My side effects from previous treatments are mild or gone.

Exclusion Criteria

I have received treatments targeting LAIR1.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NGM438 as monotherapy and in combination with pembrolizumab in advanced or metastatic solid tumors

Approximately 24 months

Visits on Day 1, 2, 4, 8, and 15 of Cycles 1 and 3, Day 1 of Cycle 2, and Day 1 of Cycles 4-6 and every third cycle thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NGM438
• Pembrolizumab

Trial Overview The study is testing NGM438 alone and combined with Pembrolizumab on various cancers like lung, breast, prostate, melanoma, etc., to see how well these treatments work against advanced stages of the diseases.

How Is the Trial Designed?

Group I: NGM438 Monotherapy Dose Escalation Experimental Treatment 1 Intervention

Part 1a Single Agent Dose Escalation

Group II: NGM438 Combination Dose Finding with pembrolizumab ( KEYTRUDA ® ) Experimental Treatment 2 Interventions

Part 1b NGM438 plus pembrolizumab ( KEYTRUDA ® )

Group III: Biopsy Cohort with NGM438 Monotherapy Followed by Combination Therapy with Pembrolizumab(KEYTRUDA ®) Experimental Treatment 2 Interventions

Part 1C NGM438 followed by NGM438 plus pembrolizumab ( KEYTRUDA ® )

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 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]

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) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

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, an immune checkpoint inhibitor for non-small cell lung carcinoma, has been linked to adverse renal outcomes, including acute kidney injury.

In a reported case, a patient developed acute tubulointerstitial nephritis after starting pembrolizumab, and while renal function improved with long-term corticosteroid treatment after discontinuation of the drug, it only improved partially.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Tubulointerstitial Nephritis: A Case Report on Rare Adverse Effect of Pembrolizumab. Basnet, S., Dhital, R., Tharu, B.[2020]

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]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/82/12_Supplement/LB219/704677/Abstract-LB219-Preclinical-development-of-NGM438-a

Preclinical development of NGM438, a novel anti-LAIR1 ... NGM438 is a novel LAIR1 antagonist mAb that reverses collagen-based immune suppression. LAIR1 was expressed on cancer patient circulating and intratumoral ...

2. ngmbio.com ngmbio.com/wp-content/uploads/2024/07/Rodriguez-Rivera-et-al-Mol-Cancer-Ther-2024-Anti-tumor-activity-of-a-novel-LAIR1-antagonist-in-combination-with-anti-PD-1-to-treat-collagen-rich-solid-tumors.pdf

Anti-tumor activity of a novel LAIR1 antagonist in ... Further, a mouse-reactive NGM438 surrogate antibody sensitized refractory KP mouse lung tumors to anti-PD-1 therapy and resulted in increased intratumoral CD8+ ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05311618

NCT05311618 | Study of NGM438 as Monotherapy and in ... Incidence and titers of anti-drug antibodies (ADA) against NGM438. Will be measured on Day 1 of each cycle through Cycle 6 and every third cycle thereafter.

4. drugdiscoverynews.com drugdiscoverynews.com/introducing-ngm438-14962

Introducing NGM438 NGM Biopharmaceuticals recently disclosed its third oncology development candidate: NGM438, a novel antagonist antibody that inhibits leukocyte-associated ...

5. biospace.com biospace.com/ngm-bio-announces-initiation-of-phase-1-1b-clinical-study-of-ngm438-for-the-treatment-of-patients-with-advanced-solid-tumors

NGM Bio Announces Initiation of Phase 1/1b Clinical Study ... NGM438 is an antagonist antibody product candidate engineered to inhibit LAIR1 being developed by NGM Bio for the treatment of advanced solid ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38648067/

Antitumor Activity of a Novel LAIR1 Antagonist in ... - PubMed NGM438, a novel humanized LAIR1 antagonist mAb, elicits myeloid inflammation and allogeneic T-cell responses by binding to LAIR1 and blocking collagen ...