Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Yale University
Must be taking:PD-1 inhibitors
Must not be taking: Immunosuppressants
Disqualifiers: CNS metastases, Leptomeningeal carcinomatosis, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing a new drug, NC318, alone or with Pembrolizumab, in patients with advanced lung cancer. It aims to help those who haven't responded to other treatments or have specific tumor characteristics. The drugs work by enhancing the immune system's ability to attack cancer cells.
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.
What data supports the effectiveness of the drug pembrolizumab for lung cancer?
Research shows that pembrolizumab, a drug that helps the immune system fight cancer, improves survival and slows disease progression in patients with advanced non-small cell lung cancer. It is especially effective in patients whose tumors have high levels of a protein called PD-L1.
12345Is the combination of NC318 and Pembrolizumab safe for humans?
Pembrolizumab (also known as Keytruda) has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and more serious immune-related issues like lung inflammation (pneumonitis) and liver inflammation (hepatitis). While specific safety data for the combination with NC318 is not provided, pembrolizumab's safety profile is well-documented in other conditions.
12467What makes the drug combination of NC318 and pembrolizumab unique for lung cancer treatment?
The combination of NC318 and pembrolizumab is unique because it involves using pembrolizumab, a drug that blocks a pathway (PD-1/PD-L1) to help the immune system attack cancer cells, alongside NC318, which may target different aspects of the tumor environment, potentially enhancing the overall treatment effect for lung cancer.
12489Eligibility Criteria
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 lung cancer is advanced or has spread to other areas.
I am willing to have a biopsy on at least one of my tumors.
I have had PD-1 inhibitor therapy and my cancer progressed afterwards.
I am fully active or can carry out light work.
Exclusion Criteria
I had a severe reaction to previous immunotherapy.
I have never received PD-1 axis inhibitor therapy.
I had radiation therapy not targeting the brain within the last 2 weeks.
I have brain metastases that are causing symptoms or have not been treated.
I have had cancer spread to the lining of my brain and spinal cord.
Participant Groups
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.
5Treatment groups
Experimental Treatment
Group I: Arm 2a (naïve to PD-1 axis inhibitor)- NC318 and PembrolizumabExperimental Treatment2 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 PembrolizumabExperimental Treatment2 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 PembrolizumabExperimental Treatment1 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 PembrolizumabExperimental Treatment2 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 onlyExperimental Treatment1 Intervention
At the discretion of the treating physician, advanced NSCLC patients on arm 1a will receive NC318 alone.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Yale UniversityNew Haven, CT
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Who is running the clinical trial?
Yale UniversityLead Sponsor
National Cancer Institute (NCI)Collaborator
NextCure, Inc.Industry Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
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. [2022]Pembrolizumab is a standard-of-care for advanced non-small-cell lung cancer (NSCLC). We assessed pembrolizumab as adjuvant therapy for completely resected stage IB-IIIA NSCLC.
FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co., Inc., https://www.merck.com) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors express programmed death-ligand 1 (PD-L1) as determined by an FDA-approved test, as follows: (a) first-line treatment of patients with mNSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, and (b) treatment of patients with mNSCLC whose tumors express PD-L1 (TPS ≥1%), with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.Approval was based on two randomized, open-label, active-controlled trials demonstrating statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients randomized to pembrolizumab compared with chemotherapy. In KEYNOTE-024, patients with previously untreated mNSCLC who received pembrolizumab (200 mg intravenously [IV] every 3 weeks) had a statistically significant improvement in OS (hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.41-0.89; p = .005), and significant improvement in PFS (HR 0.50; 95% CI: 0.37-0.68; p < .001). In KEYNOTE-010, patients with disease progression on or after platinum-containing chemotherapy received pembrolizumab IV 2 mg/kg, 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks. The HR and p value for OS was 0.71 (95% CI: 0.58-0.88), p < .001 comparing pembrolizumab 2 mg/kg with chemotherapy and the HR and p value for OS was 0.61 (95% CI: 0.49-0.75), p < .001 comparing pembrolizumab 10 mg/kg with chemotherapy.
Pembrolizumab Shows Promise for NSCLC. [2015]Data from the KEYNOTE-001 trial show that pembrolizumab improves clinical outcomes for patients with advanced non-small cell lung cancer, and is well tolerated. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]Pembrolizumab is a programmed death receptor-1 masking antibody approved for metastatic non-small cell lung cancer. This Phase 2 study (NCT02818920) of neoadjuvant pembrolizumab in non-small cell lung cancer had a primary end point of safety and secondary end points of efficacy and correlative science.
[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]Pembrolizumab, a humanized monoclonal antibody IgG4 anti-PD-1, having offered promising results in patients suffering from non-small cell lung cancer metastatic and heavily pretreated.