NGM707 + Pembrolizumab for Cancer

Not currently recruiting at 44 trial locations

Overseen By NGM Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: NGM Biopharmaceuticals, Inc

Must not be taking: ILT2, ILT4, HLA-G

Disqualifiers: Others

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

Compensation: Varies

Number of Visits: 1

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of a new treatment called NGM707, either alone or combined with pembrolizumab (KEYTRUDA®), for advanced or metastatic solid tumors. The goal is to determine the effectiveness and safety of these treatments for various cancers, including lung, head and neck, kidney, colon, and ovarian cancers. Individuals with solid tumor cancer that has worsened despite other treatments might be suitable for this trial. Participants should have good kidney, liver, and bone marrow function and must not have previously received treatments targeting certain immune checkpoints. As a Phase 1 trial, this research aims to understand 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. 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 NGM707, used alone or with pembrolizumab, is safe and well-tolerated at various doses. In these studies, participants with advanced or metastatic solid tumors received the treatment, and the results were encouraging. No serious side effects specific to the combination have been reported.

Moreover, pembrolizumab, part of the combination treatment, has already received FDA approval for other cancers, indicating its safety in those cases. Overall, the evidence suggests that this treatment is generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NGM707 because it introduces a novel approach in cancer treatment by targeting immune checkpoints that are distinct from those affected by current options like PD-1 or PD-L1 inhibitors. Unlike standard treatments, NGM707 works by potentially enhancing the immune system's ability to recognize and attack cancer cells by blocking the interactions of specific immune-regulatory proteins. Combined with pembrolizumab (KEYTRUDA®), which is already a well-known PD-1 inhibitor, this combination aims to provide a dual blockade that could offer enhanced anti-tumor activity. This innovative mechanism provides hope for treating various cancer types like NSCLC, SCCHN, RCC, CRC, and ovarian cancer more effectively.

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

Research shows that NGM707, when combined with pembrolizumab, shows early signs of effectiveness in treating advanced solid tumors. In this trial, participants may receive this combination, which studies have found safe and well-tolerated at various doses. Early results suggest this combination may alter myeloid cells, a type of immune cell, to enhance their ability to fight cancer. Additionally, NGM707 is being tested alone in this trial for several cancers, including kidney and ovarian cancer. Initial findings suggest it may help by targeting specific cancer pathways. Both treatments remain under study, but early data is promising. ^{4 6 7 8 9}

Who Is on the Research Team?

Chief Medical Officer

Principal Investigator

NGM Biopharmaceuticals, Inc

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, or can't tolerate them, and are in good physical condition. They must have recovered from previous therapy side effects and have proper bone marrow, kidney, and liver function.

Inclusion Criteria

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

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

My cancer did not respond to or I couldn't tolerate all treatments I was eligible for.

Exclusion Criteria

I have not had treatments targeting ILT2/ILT4 or HLA-G.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NGM707 as monotherapy or in combination with pembrolizumab for advanced or metastatic solid tumor malignancies

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 Cycle 4 and each cycle thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• NGM707
• Pembrolizumab

Trial Overview The study tests NGM707 alone or combined with pembrolizumab to treat various cancers. It aims to see how well these treatments work on their own or together against different types of advanced cancer.

How Is the Trial Designed?

Group I: NGM707 Monotherapy Dose Expansion Arm F Experimental Treatment 1 Intervention

NGM707 in Ovarian

Group II: NGM707 Monotherapy Dose Expansion Arm E Experimental Treatment 1 Intervention

NGM707 in CRC

Group III: NGM707 Monotherapy Dose Expansion Arm D Experimental Treatment 1 Intervention

NGM707 in RCC

Group IV: NGM707 Monotherapy Dose Escalation Experimental Treatment 1 Intervention

Part 1a Single Agent Dose Escalation

Group V: NGM707 Combination Dose Finding with pembrolizumab (KEYTRUDA®) Experimental Treatment 1 Intervention

Part 1b NGM707 plus pembrolizumab (KEYTRUDA®)

Group VI: NGM707 Combination Dose Expansion Arm C Experimental Treatment 1 Intervention

NGM707 with pembrolizumab (KEYTRUDA®) in SCCHN

Group VII: NGM707 Combination Dose Expansion Arm B Experimental Treatment 1 Intervention

NGM707 with pembrolizumab (KEYTRUDA®) in Non-Squamous NSCLC

Group VIII: NGM707 Combination Dose Expansion Arm A Experimental Treatment 1 Intervention

NGM707 with pembrolizumab (KEYTRUDA®) in Squamous NSCLC

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 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 (MK-3475) is a monoclonal antibody that blocks PD-1, which helps the immune system fight cancer by preventing tumor cells from evading immune responses; it has shown high tumor response rates in advanced melanoma and non-small cell lung cancer.

The drug received accelerated FDA approval due to its effectiveness in early clinical trials, demonstrating long-lasting effects in patients who had previously been treated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: PD-1 inhibition as a therapeutic strategy in cancer. McDermott, J., Jimeno, A.[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 (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 (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 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]

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, 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04913337

NCT04913337 | Study of NGM707 As Monotherapy and in ... A Phase 1/2 Dose Escalation/Expansion Study of NGM707 As Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies

2. ngmbio.com ngmbio.com/wp-content/uploads/2024/04/AACR-2024-Poster1-NGM707-Clinical-Results.pdf

NGM707 in Combination With Pembrolizumab in ... In this advanced and metastatic solid tumor cohort, early efficacy signals have been observed. Evidence of myeloid cell reprogramming was observed in paired ...

3. delta.larvol.com delta.larvol.com/Products/?ProductId=de175dbd-2a61-4800-bda1-8752025b0590

NGM707 / NGM Biopharma Enrollment status • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor ... Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and ...

4. clinicaltrials.eu clinicaltrials.eu/inn/ngm707/

NGM707: A Promising New Drug for Advanced Solid Tumors It is being studied for various types of cancer, including non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, ...

5. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04913337/

Clinical Trial: NCT04913337 Study of NGM707 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04913337

NCT04913337 | Study of NGM707 As Monotherapy and in ... A Phase 1/2 Dose Escalation/Expansion Study of NGM707 As Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2582

Phase 1/2 study of NGM707, an ILT2/ILT4 dual antagonist ... Conclusions: NGM707 as monotherapy and in combination with pembrolizumab was safe and well tolerated at all dose levels. In heavily pretreated ...

8. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT099/742554/Abstract-CT099-NGM707-in-combination-with

Abstract CT099: NGM707 in combination with pembrolizumab ... NGM707 in combination with pembrolizumab appears to be safe and well tolerated at all dose levels. In this advanced and metastatic solid tumor cohort, early ...

9. esmoiotech.org esmoiotech.org/article/S2590-0188(22)00217-9/fulltext

174P First-in-human study of NGM707, an ILT2/ILT4 dual ... First-in-human study of NGM707, an ILT2/ILT4 dual antagonist antibody in advanced or metastatic solid tumors: Preliminary monotherapy dose escalation data