The Study of NC318 Alone or in Combination With Pembrolizumab in Patients With Advanced Non-small Cell Lung Cancer

NCT04699123 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 20000282062P50CA196530-06
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2 study to investigate NC318 alone or in combination with Pembrolizumab in patients with advanced non-small cell lung cancer.

Conditions

Advanced Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (9)

• Objective response rate (ORR) in Arm 1a

  To determine the objective response rate (ORR) using RECIST v1.1 to NC318 in arm 1a

  Tumor response will be based on tumor assessments at screening, every 8 weeks from the first dose (for the first 24 weeks) and thereafter every 12 weeks until investigator-assessed initial disease progression, up to 4 years

• Objective response rate (ORR) in Arm 1b

  To determine the objective response rate (ORR) using RECIST v1.1 to NC318 combined with pembrolizumab in arm 1b

  Tumor response will be based on tumor assessments at screening, every 8 weeks from the first dose (for the first 24 weeks) and thereafter every 12 weeks until investigator-assessed initial disease progression, up to 4 years

• Objective response rate (ORR) in Arm 1c

  To determine the objective response rate (ORR) using RECIST v1.1 to NC318 combined with pembrolizumab in arm 1b

  Tumor response will be based on tumor assessments at screening, every 8 weeks from the first dose (for the first 24 weeks) and thereafter every 12 weeks until investigator-assessed initial disease progression, up to 4 years

• Number of participants on Arm 1b with treatment related adverse events as assessed by CTCAE v5

  To determine the safety of NC318 when administered in combination with pembrolizumab in arm 1b

  Safety run in of 6 weeks

• Number of participants on Arm 1c with treatment related adverse events as assessed by CTCAE v5

  To determine the safety of NC318 when administered in combination with pembrolizumab in arm 1b

  Safety run in of 6 weeks

• Objective response rate (ORR) in Arm 2

  To determine the objective response rate (ORR) using RECIST v1.1 to NC318 combined with pembrolizumab in arm 2

  Tumor response will be based on tumor assessments at screening, every 8 weeks from the first dose (for the first 24 weeks) and thereafter every 12 weeks until investigator-assessed initial disease progression, up to 4 years

• Objective response rate (ORR) in Arm 2a

  To determine the objective response rate (ORR) using RECIST v1.1 to NC318 combined with pembrolizumab in arm 2

  Tumor response will be based on tumor assessments at screening, every 8 weeks from the first dose (for the first 24 weeks) and thereafter every 12 weeks until investigator-assessed initial disease progression, up to 4 years

• Number of participants in arm 2 with treatment related adverse events as assessed by CTCAE v5

  To determine the safety of NC318 when administered in combination with pembrolizumab in arm 2

  Safety run in of 6 weeks

• Number of participants in arm 2a with treatment related adverse events as assessed by CTCAE v5

  To determine the safety of NC318 when administered in combination with pembrolizumab in arm 2

  Safety run in of 6 weeks

Secondary Outcomes (6)

• Progression-free survival (RECIST v1.1) Arm 1a

  Until disease progression or death, up to 4 years

• Overall Survival (RECIST v1.1) Arm 1a

  Until death, up to 5 years

• Progression-free survival (RECIST v1.1) Arm 1B

  Until disease progression or death, up to 4 years

• Overall survival (RECIST v1.1) Arm 1B

  Until death, up to 5 years

• Progression-free survival (RECIST v1.1) Arm 2

  Until disease progression or death, up to 4 years

Study Arms (5)

Arm 1a - NC318 only

EXPERIMENTAL

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

Drug: NC318 800 mg

Arm 1b - NC318 and Pembrolizumab

EXPERIMENTAL

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

Drug: NC318 400 mg; Drug: Pembrolizumab

Arm 1c - NC318 and Pembrolizumab

EXPERIMENTAL

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

Drug: NC318 800 mg

Arm 2 (naïve to PD-1 axis inhibitor)- NC318 and Pembrolizumab

EXPERIMENTAL

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.

Drug: NC318 400 mg; Drug: Pembrolizumab

Arm 2a (naïve to PD-1 axis inhibitor)- NC318 and Pembrolizumab

EXPERIMENTAL

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.

Drug: NC318 800 mg; Drug: Pembrolizumab

Interventions

NC318 800 mg DRUG

NC318 will be given intravenously (IV) weekly for 8 doses and then every 2 weeks for patients receiving combination therapy treatment or weekly for patient receiving NC318 in monotherapy.

Arm 1a - NC318 only; Arm 1c - NC318 and Pembrolizumab; Arm 2a (naïve to PD-1 axis inhibitor)- NC318 and Pembrolizumab

NC318 400 mg DRUG

NC318 will be given intravenously (IV) every 2 weeks.

Arm 1b - NC318 and Pembrolizumab; Arm 2 (naïve to PD-1 axis inhibitor)- NC318 and Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab 200 mg will be given IV every 3 weeks

Arm 1b - NC318 and Pembrolizumab; Arm 2 (naïve to PD-1 axis inhibitor)- NC318 and Pembrolizumab; Arm 2a (naïve to PD-1 axis inhibitor)- NC318 and Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically documented, locally advanced or metastatic (i.e., Stage IIIB not eligible for definitive chemoradiotherapy, Stage IV, or recurrent) NSCLC (per the American Joint Committee /AJCC staging system)
• ECOG performance status of 0 to 1
• Measurable disease per RECIST v1.1 criteria
• Arm 1a, and 1b and 1c: Prior PD-1 axis inhibitor therapy (anti-PD-1 or anti-PD-L1, e.g. nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab) either alone or in combination with other systemic agents, with documented progressive disease.
• Arm 2a: PD-L1 expression of less than 50 percent (PD-1 axis inhibitor therapy naïve)
• Patients with NSCLC known to harbor an ALK rearrangement, ROS1 rearrangement, EGFR mutation or BRAF mutation known to be sensitive to FDA approved tyrosine kinase inhibitors (TKI), are only eligible after experiencing disease progression (during or after treatment) or intolerance to respective TKI:
• Patients with TKI treated EGFR mutant NSCLC harboring the secondary EGFR T790M tumor must have received prior osimertinib.
• Patients with crizotinib treated ALK rearranged NSCLC must have received a next generation ALK inhibitor (e.g. ceritinib, alectinib, brigatinib or lorlatinib).
• At least one tumor amenable to incisional, excisional, core or forceps (transbronchial) biopsy. Patients must be willing to undergo a tumor biopsy before starting trial therapy and at the time of disease progression.
• Adequate hematologic and end-organ function

You may not qualify if:

• Subjects must not have a history of life-threatening toxicity related to prior anti-PD-1 axis therapy:
• a. Subjects with history of anti-PD-1 axis therapy toxicities that are unlikely to recur with standard countermeasures (e.g., hormone replacement after adrenal crisis) are eligible.
• Symptomatic or untreated CNS metastases. Patients with a history of treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:
• No evidence of interim progression between the completion of CNS-directed therapy and the start of trial therapy
• No ongoing requirement for dexamethasone as therapy for CNS disease; anticonvulsants at a stable dose are allowed.
• Completed stereotactic radiosurgery at least 1 week prior to initiation of trial therapyCycle 1, Day 1 or whole-brain radiation at least 2 weeks prior to initiation of trial therapyCycle 1, Day 1.
• History of leptomeningeal carcinomatosis
• Prior palliative radiotherapy outside the CNS within 2 weeks of the first dose of study drug
• Treatment with systemic immunosuppressive medications (including but not limited to, dexamethasone at doses \> 2 mg daily (or equivalent dose of other corticosteroids), cyclophosphamide, tacrolimus, sirolimus, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to initiating trial therapy. (Inhaled or topically applied steroids, and acute and chronic standard-dose NSAIDs are permitted. Replacement steroids are also permitted). Prophylactic corticosteroids prior to imaging with intravenous contrast are allowed per institutional guidelines, without need for delay of 2 weeks. Arm 2a: No prior PD-1 axis inhibitor therapy

Sponsors & Collaborators

• Yale University: lead
• National Cancer Institute (NCI): collaborator
• NextCure, Inc.: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06492, United States

Location

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Scott Gettinger

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Internal Medicine (Medical Oncology)

Study Record Dates

• First Submitted: December 16, 2020
• First Posted: January 7, 2021
• Study Start: February 4, 2021
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: May 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)