NTX-1088 + Pembrolizumab for Cancer

Recruiting at 4 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

Trial Summary

What is the purpose of this trial?

This trial tests NTX-1088, alone or with pembrolizumab, in patients with advanced solid cancers. NTX-1088 helps the immune system find and attack cancer cells, while pembrolizumab boosts the immune system's ability to fight cancer.

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.

What data supports the effectiveness of the drug pembrolizumab in cancer treatment?

Pembrolizumab has been shown to improve survival in patients with non-small cell lung cancer and is approved for use in esophageal cancer, demonstrating its effectiveness in treating certain types of cancer. ^{1 2 3 4 5}

Is the combination of NTX-1088 and Pembrolizumab safe for humans?

Pembrolizumab (also known as KEYTRUDA) has been used in various clinical trials for different cancers, showing common side effects like fatigue, cough, nausea, and rash. More serious immune-related side effects can include lung inflammation, liver inflammation, and thyroid issues. While these studies provide safety data for Pembrolizumab, specific safety data for the combination with NTX-1088 is not available. ^{1 3 4 6 7}

What makes the drug NTX-1088 + Pembrolizumab unique for cancer treatment?

The combination of NTX-1088 with Pembrolizumab is unique because it pairs a novel treatment (NTX-1088) with Pembrolizumab, a well-established immune checkpoint inhibitor that blocks the PD-1 pathway, enhancing the immune system's ability to fight cancer. This combination may offer a new approach to treating cancers that are resistant to standard therapies. ^{1 3 4 8 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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 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) 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

3. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

5. United States 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]