NC410 + Pembrolizumab for Advanced Cancer

Recruiting at 16 trial locations

Overseen By Director Clinical Operations at NextCure, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: NextCure, Inc.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Active infection, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 24 months

97 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received certain cancer therapies or vaccines within specific timeframes before starting the study treatment.

What data supports the effectiveness of the drug pembrolizumab in treating advanced cancer?

Research shows that pembrolizumab, a drug that helps the immune system fight cancer, has been effective in improving survival and response rates in patients with advanced non-small cell lung cancer and melanoma. It has shown promise in various solid tumors, suggesting potential benefits for other advanced cancers as well. ^{1 2 3 4 5}

Is the combination of NC410 and Pembrolizumab safe for humans?

Pembrolizumab (also known as Keytruda or MK-3475) has been shown to be generally safe in humans, with common side effects including fatigue, cough, nausea, and rash. Some serious side effects can occur, such as inflammation of the lungs (pneumonitis), liver (hepatitis), or intestines (colitis), and issues with hormone glands, but these are less common. ^{1 2 6 7 8}

What makes the drug NC410 + Pembrolizumab unique for advanced cancer treatment?

The combination of NC410 and Pembrolizumab is unique because it involves a novel approach by combining a new treatment (NC410) with Pembrolizumab, a well-established immune checkpoint inhibitor that targets the PD-1/PD-L1 pathway, which has shown effectiveness in various cancers. This combination aims to enhance the immune system's ability to fight cancer, potentially offering a new option for patients with advanced cancer. ^{1 2 7 9 10}

What is the purpose of this trial?

This is an open-label, non-randomized, Phase 1b/2 study to determine the safety and tolerability of NC410 when combined with a standard dose of pembrolizumab. This study will also assess the clinical benefit of combination therapy in participants with advanced unresectable and/or metastatic ICI refractory solid tumors OR ICI naïve MSS/MSI-low solid tumors

Research Team

Udayan Guha, MD

Principal Investigator

NextCure, Inc.

Eligibility Criteria

Adults with advanced unresectable/metastatic solid tumors, including specific cancers like colorectal, stomach, esophageal, and ovarian. Participants must have progressed after standard therapy or be ICI refractory. They should agree to contraception use and not expect a child soon. Adequate organ function and an ECOG status of 0-1 are required.

Inclusion Criteria

My cancer is not highly mutated and has worsened after treatment.

My organs are functioning well.

My cancer is advanced, cannot be surgically removed, and may have spread.

Exclusion Criteria

I have or had lung inflammation that needed steroids.

I am currently being treated for an infection.

I have received a transplant from another person.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NC410 and pembrolizumab until a reason for treatment discontinuation is reached

up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• NC410
• Pembrolizumab

Trial Overview The trial is testing the combination of NC410 with Pembrolizumab for safety, tolerability, and effectiveness in treating various advanced solid tumors that are either resistant to immune checkpoint inhibitors (ICIs) or haven't been treated with ICIs if they're microsatellite stable/low.

Participant Groups

Group I: NC410 and pembrolizumab Experimental Treatment 2 Interventions

All participants will receive NC410 (IV) and pembrolizumab (IV) according to the treatment schedule until a reason for treatment discontinuation is reached.

Who Is Running the Clinical Trial?

NextCure, Inc.

Lead Sponsor

Trials

8

Recruited

660+

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

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]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., 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]

In the KEYNOTE-024 study involving 305 patients with untreated advanced non-small-cell lung cancer, pembrolizumab significantly improved overall survival (OS) compared to platinum-based chemotherapy, with a median OS of 30.0 months versus 14.2 months for chemotherapy.

Pembrolizumab also had a better safety profile, with fewer treatment-related severe adverse events (31.2% for pembrolizumab vs. 53.3% for chemotherapy), indicating it is a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[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]

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]

A study of 219 patients with advanced non-small-cell lung cancer (NSCLC) receiving first-line pembrolizumab found that a simple score combining albumin and neutrophil count (Scottish Inflammatory Prognostic Score, SIPS) can effectively predict progression-free survival (PFS) and overall survival (OS).

Patients with a higher SIPS score (indicating lower albumin and higher neutrophil counts) had significantly worse survival outcomes, with PFS ranging from 17.9 months for SIPS0 to 2.5 months for SIPS2, highlighting the score's potential to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers of systemic inflammation predict survival with first-line immune checkpoint inhibitors in non-small-cell lung cancer. Stares, M., Ding, TE., Stratton, C., et al.[2022]

In a phase II study involving 110 patients with advanced clear cell renal cell carcinoma (ccRCC), pembrolizumab demonstrated a 36.4% objective response rate, indicating significant antitumor activity as a first-line treatment.

The treatment was generally well-tolerated, with 30% of patients experiencing grade 3-5 adverse events, primarily colitis and diarrhea, which aligns with safety profiles observed in other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. McDermott, DF., Lee, JL., Bjarnason, GA., et al.[2022]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]

4. United States 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. [2022]

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

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]

7. 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]

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

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

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

Biomarkers of systemic inflammation predict survival with first-line immune checkpoint inhibitors in non-small-cell lung cancer. [2022]

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

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. [2022]