Study of GT103 in Combination With Pembrolizumab in Refractory, Metastatic Non-Small Cell Lung Cancer

NCT05617313 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: PRO00109146HCRN LUN21-497
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 6

Brief Summary

This open-label, non-randomized Phase II trial is designed to assess the safety and tolerability of GT103 in combination with pembrolizumab in adult subjects with relapsed or refractory, metastatic NSCLC. The study will consist of a safety lead-in of 10-20 patients. A total of 50 patients will be treated with the combination at the safest dose of GT103 as determined in the safety lead-in. If 10 additional patients are enrolled to the dose level -1 then the maximum of 60 subjects may be accrued to this trial.

Conditions

Non Small Cell Lung Cancer; Metastatic NSCLC; Recurrent Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  ORR will be defined as the proportion of patients with radiographic complete or partial response rate per RECIST v1.1.

  3 years

• Assess the Frequency and Severity of Adverse Events

  Safety and tolerability will be assessed by the proportion of patients with DLT observed during the first cycle of treatment. NCI CTCAE v5 will be used to grade adverse events.

  6 months

Secondary Outcomes (6)

• Characterize PK Profile: T1/2 of GT103 in combination with Pembrolizumab

  6 months

• Characterize PK Profile: Tmax of GT103 in combination with Pembrolizumab

  6 months

• Characterize PK Profile: Peak Plasma Concentration (Cmax)

  6 months

• Characterize PK Profile: Area Under the Plasma Concentration vs Time Curve (AUC)

  6 months

• Progression Free Survival (PFS)

  4 years

Study Arms (1)

Experimental Group

EXPERIMENTAL

Pembrolizumab will be given intravenously on Day 1 of the 21 day cycle (For all cycles). GT103 dose will be determined by the safety lead in prior to the study. Dosing calculations should be based on actual body weight where applicable. It will be taken intravenously on Day 1 of the 21 day cycle (For all cycles).

Drug: Pembrolizumab; Drug: GT103

Interventions

Pembrolizumab DRUG

200 mg intravenously on Day 1 of cycle.

Also known as: Keytruda

Experimental Group

GT103 DRUG

10mg/kg taken intravenously on Day 1 of cycle.

Experimental Group

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status 0 or 1 within 14 days prior to registration.
• Histologically and/or cytologically confirmed Stage III-IV recurrent or metastatic NSCLC (American Joint Committee on Cancer (AJCC) Staging Manual 8th ed).
• Relapsed or refractory to immunotherapy. NOTE: anti-PD-1/PD-L1; prior anti-CTLA4 therapy is permitted; a minimum of 2 doses of prior immunotherapy is required. Prior treatment with chemotherapy is permitted. Neoadjuvant or adjuvant therapy is considered a line of treatment if given within 6 months of recurrent/metastatic disease. No more than 2 prior lines of therapy is permitted (this does not include oral targeted therapy).
• Patients with sensitizing EGFR, ALK, RET, ROS1, BRAF and MET exon 14 alterations must have received at least one prior oral targeted therapy and prior chemotherapy (at least one platinum doublet regimen, i.e., carboplatin/cisplatin plus pemetrexed/ paclitaxel/docetaxel/gemcitabine). NOTE: Oral targeted therapies do not count as lines of treatment, with the exception of KRAS G12C agents (sotorasib, adagrasib, similar do count toward lines of treatment). No more than 2 prior lines of therapy is permitted.
• Disease must be measurable by RECIST 1.1 criteria. Tumor lesions in a previously irradiated area are considered measurable IF progression has been demonstrated in such lesions after radiation.
• Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 14 days prior to C1D1.
• Hematological
• Absolute Neutrophil Count (ANC): ≥1500/µL
• Platelet Count: ≥100 000/µL
• Hemoglobin (Hgb): ≥ 9 g/dL; Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
• Renal
• Serum creatinine OR Calculated creatinine clearance: ≤ 1.5 × ULN OR ≥ 30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
• Hepatic

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Patients currently receiving anticancer therapies or who have received anticancer therapies within 14 days prior to day 1 of study drug (including investigational agents, chemotherapy, and antibody-based therapy).
• Radiation therapy within 14 days prior to day 1 of study drug. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
• Intolerance to pembrolizumab or other PD-1/PD-L1 axis drug(s), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immune-stimulatory anti-tumor agents.
• Known auto-immune conditions requiring systemic immune suppression therapy other than prednisone ≤10 mg daily (or equivalent).
• History of (non-infectious) interstitial pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Receipt of allogeneic transplant (stem cell transplantation or solid organ).
• Current use of medications specified by the protocol as prohibited for administration in combination with the study drugs. This includes patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to day 1 of study drug. Inhaled or topical steroids and adrenal replacement doses \>10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS), hepatitis C virus (allowed if received curative therapy), acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment. NOTE: no testing for Hepatitis B, Hepatitis C or HIV is required unless mandated by local health authority.
• Current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment on Day 1 of study drug. Patients receiving prophylactic antibiotics (e.g., for prevention of urinary tract infection or chronic obstructive pulmonary disease) are eligible.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial.
• Known active CNS metastases which are symptomatic. Eligible if metastases have been locally treated 14 days prior to Cycle 1 Day 1, are clinically controlled, or asymptomatic on Cycle 1 Day. Steroid dose must be equivalent of ≤10 mg prednisone daily or equivalent dose steroid. Untreated, asymptomatic brain metastases allowed if subject does not require corticosteroids or anticonvulsant therapy.
• History of myocardial infarction, NYHA class III or IV congestive heart failure, or unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to study enrollment.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.

Sponsors & Collaborators

• Jeffrey Clarke: lead
• Merck Sharp & Dohme LLC: collaborator
• Grid Therapeutics: collaborator

Study Sites (6)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Karmanos Cancer Center (Wayne State University)

Detroit, Michigan, 48201, United States

Location

Summit Health

Berkeley Heights, New Jersey, 07922, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jeffrey Clarke, MD

  Duke Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: November 15, 2022
• Study Start: February 17, 2023
• Primary Completion: June 26, 2025
• Study Completion: June 26, 2025
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)