NTX-1088 + Pembrolizumab for Cancer

Recruiting at 5 trial locations

Overseen By Keren Paz, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nectin Therapeutics Ltd

Must not be taking: Cytotoxic chemotherapy, Monoclonal antibodies

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 2

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, NTX-1088, both alone and with pembrolizumab (an immunotherapy), for individuals with serious solid tumors that have spread or cannot be removed. The study aims to determine the optimal dose and treatment schedule for these drugs. It seeks participants with specific cancers, such as lung or kidney cancer, who have not responded to other treatments. Participants should have cancer that impacts their daily life and are looking for new options. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on certain cancer treatments or immunosuppressive therapies when starting the trial.

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

Research has shown that NTX-1088 has been safe in early testing when used alone. It aids the body's immune system in fighting cancer. In these studies, patients generally tolerated the treatment well, and no unexpected side effects have been reported so far.

The safety of NTX-1088 combined with pembrolizumab, a drug already approved for various cancers, is still under investigation. Pembrolizumab is known to be effective and is usually well-tolerated in its approved uses. However, specific safety information for the combination of NTX-1088 and pembrolizumab is not yet available, as this combination remains in the early testing stages.

In the first phase of testing, the primary goal is to assess the safety of NTX-1088 for humans and determine the appropriate dose. Results so far appear promising, but more information is needed to fully understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NTX-1088 because it offers a novel approach to cancer treatment. Unlike current options that predominantly focus on targeting cancer cells directly, NTX-1088 is designed to work by enhancing the body's immune response against cancer. This is achieved through a new mechanism of action, potentially offering a more effective and targeted approach to fighting cancer. Additionally, when used in combination with pembrolizumab, a well-known immunotherapy drug, NTX-1088 may boost the overall effectiveness of the treatment, providing new hope for better outcomes in cancer therapy.

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

Research shows that NTX-1088 is a promising new treatment for solid tumors. It targets a protein called PVR, which typically helps cancer evade the immune system. By blocking PVR, NTX-1088 enables the immune system to better attack cancer cells. Early studies have demonstrated that NTX-1088 can enhance the immune system's ability to fight tumors by restoring levels of DNAM1, a key molecule for immune response.

In this trial, some participants will receive NTX-1088 as a monotherapy, while others will receive it in combination with pembrolizumab, a well-known cancer treatment. Pembrolizumab has already been shown to extend the lives of patients with certain types of cancer, such as non-small cell lung cancer and esophageal cancer. Together, NTX-1088 and pembrolizumab could form a strong combination against advanced cancers. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with advanced solid cancers that express PVR, who have tried standard treatments without success or for whom no standard treatment is available. They must be in good physical condition (ECOG ≤1), not pregnant or breastfeeding, agree to use contraception, and have tumors measurable by RECIST 1.1.

Inclusion Criteria

Adherence to study visit schedule and other protocol requirements

My blood, kidney, and liver tests are within normal ranges.

Disease measurable by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1

Exclusion Criteria

My brain metastases are stable after treatment.

Active autoimmune disease requiring systemic treatment in the past

I had radiotherapy less than 2 weeks ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Phase

NTX-1088 administered as a 60-minute IV infusion at escalating doses as monotherapy or in combination with pembrolizumab

21 days per cycle

1 visit per cycle (in-person)

Dose Expansion Phase

NTX-1088 administered at the RP2D as a 60-minute IV infusion as monotherapy or in combination with pembrolizumab

21 days per cycle

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after the last dose

What Are the Treatments Tested in This Trial?

Interventions

• NTX-1088
• Pembrolizumab

Trial Overview

The trial studies NTX-1088 alone and combined with Pembrolizumab in patients with advanced solid malignancies. It's a two-part study: first testing different doses of NTX-1088 (dose escalation) and then expanding the trial to more patients at the chosen dose.

How Is the Trial Designed?

Group I: Part 2 - Dose Expansion (Monotherapy) Experimental Treatment 1 Intervention

NTX-1088 administered at the RP2D as a 60-minute IV infusion as a monotherapy.

Group II: Part 2 - Dose Expansion (Combination Therapy) Experimental Treatment 2 Interventions

NTX-1088 administered at the RP2D as a 60-minute IV infusion in combination with pembrolizumab at the standard labeled dose.

Group III: Part 1 - Dose Escalation Phase (Monotherapy) Experimental Treatment 1 Intervention

NTX-1088 administered as a 60-minute IV infusion at escalating doses as a monotherapy. NTX-1088 will be administered on Day 1 of a 21-day cycle.

Group IV: Part 1 - Dose Escalation Phase (Combination Therapy) Experimental Treatment 2 Interventions

NTX-1088 administered as a 60-minute IV infusion in escalating doses in combination with pembrolizumab. NTX-1088 will be administered on Day 1 of a 21-day cycle. Pembrolizumab will be administered as a 30-minute IV infusion, within 2 hours prior to NTX-1088 administration, at a dose of 200 mg on Day 1 of every 21-day cycle.

Who Is Running the Clinical Trial?

Nectin Therapeutics Ltd

Lead Sponsor

Trials

1

Recruited

90+

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 safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

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) 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 (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 (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

The ongoing KEYNOTE-495/KeyImPaCT study is evaluating the effectiveness of pembrolizumab combined with other therapies in advanced non-small cell lung cancer (NSCLC), with results showing varying objective response rates (ORR) based on tumor characteristics, ranging from 0-12% in low T-cell-inflamed groups to 50-60% in high T-cell-inflamed groups.

The study confirms that assessing T-cell-inflamed gene expression profiles (TcellinfGEP) and tumor mutational burden (TMB) can help identify which patients are more likely to benefit from pembrolizumab-based treatments, while the safety profiles of the combinations remain consistent with previous findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. Gutierrez, M., Lam, WS., Hellmann, MD., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., 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]

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