NC318 + Pembrolizumab for Lung Cancer

Overseen By Jennifer Pope

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must be taking: PD-1 inhibitors

Must not be taking: Immunosuppressants

Disqualifiers: CNS metastases, Leptomeningeal carcinomatosis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the effectiveness of a new treatment, NC318 (experimental treatment), alone or combined with Pembrolizumab (an immunotherapy drug), for people with advanced non-small cell lung cancer (NSCLC). The trial seeks to determine if these treatments can benefit those who have tried other therapies without success or those who have not yet tried Pembrolizumab. Ideal participants are individuals with advanced NSCLC who either had a previous treatment that stopped working or have specific genetic markers that make them eligible. Participants will receive either NC318 alone or a combination of NC318 and Pembrolizumab, based on their treatment history and doctor's advice. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to benefit from potentially effective new therapies.

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic immunosuppressive medications (like certain steroids and drugs that suppress the immune system) at least 2 weeks before starting the trial. However, inhaled or topical steroids and standard-dose NSAIDs are allowed.

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

Research has shown that NC318 is generally well-tolerated. Studies have found that patients treated with NC318, either alone or with pembrolizumab, experience no serious side effects. Reports from trials with NC318 and pembrolizumab indicate that most side effects are mild to moderate.

The FDA has already approved pembrolizumab for treating other cancers, confirming its well-known safety profile. For those receiving both NC318 and pembrolizumab, the combination remains manageable, with no unexpected safety issues.

Overall, the safety data suggest that both treatments warrant further study in treating advanced non-small cell lung cancer, though monitoring for side effects remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NC318 combined with pembrolizumab for lung cancer because it targets the PD-1 axis, which plays a key role in helping cancer cells evade the immune system. Unlike standard treatments like chemotherapy, which can affect both cancerous and healthy cells, this combination aims to enhance the body's immune response specifically against cancer cells. Pembrolizumab is already known for its success in immunotherapy, and pairing it with NC318 could potentially boost its effectiveness. This approach offers a promising alternative for patients, especially those who haven't received PD-1 inhibitors before.

What evidence suggests that this trial's treatments could be effective for advanced non-small cell lung cancer?

Research shows that NC318, one of the treatments in this trial, may help treat advanced non-small cell lung cancer (NSCLC) either alone or with pembrolizumab, another treatment option in this trial. Studies found that 28% of patients who did not respond to PD-1 inhibitors (a type of immune system treatment) experienced positive results with the NC318 and pembrolizumab combination. Pembrolizumab is already known to work well for various cancers, especially in patients with tumors that have PD-L1. This combination treatment has improved some patients' responses and overall health outcomes. The research suggests this could be a new option for people with advanced NSCLC. ^{1 2 3 5 6}

Who Is on the Research Team?

Scott N. Gettinger

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer who have tried PD-1 axis inhibitor therapy and it didn't work (except Arm 2a). They should be relatively healthy, able to undergo a biopsy, and not have used immunosuppressive drugs recently. Those with certain gene mutations after treatment failure or intolerance are also eligible.

Inclusion Criteria

My cancer progressed or I couldn't tolerate treatment after a specific gene mutation.

You have a disease that can be measured using specific criteria.

My blood and organs are functioning well.

Exclusion Criteria

I had a severe reaction to previous immunotherapy.

I haven't taken any immune-weakening drugs in the last 2 weeks.

I have never received PD-1 axis inhibitor therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Initial safety assessment of NC318 alone or in combination with pembrolizumab

6 weeks

Treatment

Participants receive NC318 alone or in combination with pembrolizumab, with tumor assessments every 8 weeks for the first 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments every 12 weeks until disease progression

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• NC318
• Pembrolizumab

Trial Overview The study is testing the effectiveness of NC318 at two different doses, either alone or combined with Pembrolizumab. It's designed to see how well these treatments can control lung cancer that has spread and isn't responding to previous therapies.

How Is the Trial Designed?

Group I: Arm 2a (naïve to PD-1 axis inhibitor)- NC318 and Pembrolizumab Experimental Treatment 2 Interventions

Arm 2a will enroll patients with advanced NSCLC who are naïve to PD-1 axis inhibitor therapy to receive combination therapy with NC318 and pembrolizumab.

Group II: Arm 2 (naïve to PD-1 axis inhibitor)- NC318 and Pembrolizumab Experimental Treatment 2 Interventions

Arm 2 will enroll patients with advanced NSCLC who are naïve to PD-1 axis inhibitor therapy to receive therapy with NC318 in combination with pembrolizumab.

Group III: Arm 1c - NC318 and Pembrolizumab Experimental Treatment 1 Intervention

At the discretion of the treating physician, advanced NSCLC patients on arm 1b will receive combination therapy with NC318 and pembrolizumab.

Group IV: Arm 1b - NC318 and Pembrolizumab Experimental Treatment 2 Interventions

At the discretion of the treating physician, advanced NSCLC patients on arm 1b will receive combination therapy with NC318 and pembrolizumab.

Group V: Arm 1a - NC318 only Experimental Treatment 1 Intervention

At the discretion of the treating physician, advanced NSCLC patients on arm 1a will receive NC318 alone.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

NextCure, Inc.

Industry 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

Published Research Related to This Trial

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

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 Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

In a phase 3 trial involving 1177 participants with completely resected stage IB-IIIA non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved median disease-free survival to 53.6 months compared to 42.0 months for placebo, indicating its efficacy as an adjuvant therapy.

The safety profile of pembrolizumab was consistent with previous studies, showing no new safety signals, although serious adverse events were more common in the pembrolizumab group (24%) compared to placebo (15%), highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. O'Brien, M., Paz-Ares, L., Marreaud, S., 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 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]

The KEYNOTE-001 trial demonstrated that pembrolizumab significantly improves clinical outcomes for patients with advanced non-small cell lung cancer, indicating its efficacy as a treatment option.

Patients whose tumors express PD-L1 in at least 50% of cells showed better responses to pembrolizumab, suggesting that PD-L1 expression is a key factor in predicting treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04699123

NCT04699123 | The Study of NC318 Alone or in ... This is a phase 2 study to investigate NC318 alone or in combination with Pembrolizumab in patients with advanced non-small cell lung cancer. Detailed ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-00074

NC318 Alone or in Combination with Pembrolizumab for ... This phase II trial tests how well NC318 works alone or in combination with pembrolizumab in treating patients with non-small cell lung cancer (NSCLC)

3. ir.nextcure.com ir.nextcure.com/news-releases/news-release-details/phase-2-study-anti-siglec-15-antibody-nc318-combination

A Phase 2 Study of Anti-Siglec-15 Antibody, NC318, in ... Efficacy data demonstrate that the combination of NC318 and pembrolizumab is active in advanced PD-1 axis inhibitor refractory NSCLC: 28% of ...

4. medicine.yale.edu medicine.yale.edu/news-article/new-immunotherapy-treatment-brings-hope-to-patients-with-advanced-non-small-cell-lung-cancer/

New Immunotherapy Treatment Brings Hope to Patients With ... The study's findings suggest that NC318, both alone and in combination with pembrolizumab, improved response rates and clinical outcomes for some patients with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04430933

A Safety and Tolerability Study of NC318 in Combination ... A Safety and Tolerability Study of NC318 in Combination With Chemotherapy for Subjects With Advanced or Metastatic NSCLC. ClinicalTrials.gov ID NCT04430933.

6. clin.larvol.com clin.larvol.com/trial-detail/NCT03665285

A Safety and Tolerability Study of NC318 in Subjects With ... The data come from clinical studies evaluating NC318, a Siglec-15 antibody, and NC410, a LAIR-2 fusion protein, in patients with advanced/metastatic solid ...