Trial Investigating Visugromab in Combination With Immunochemotherapy in 1L Treatment of Participants With Metastatic NSCLC

Official title

A Ph2, Randomized, Blinded, Placebo-Controlled Trial Investigating the Efficacy and Safety of Visugromab Versus Placebo, in Combination With Pembrolizumab, Pemetrexed, and Carboplatin, in 1L Treatment of Participants With Metastatic NSCLC (GDFATHER-NSCLC-01)

Overview

This is an exploratory, signal finding, randomized, placebo-controlled, blinded, multi-center Phase 2b trial of the anti GDF-15 antibody Visugromab (CTL-002) versus Placebo, combined with Immunochemotherapy (ICT: Pembrolizumab, Pemetrexed, Carboplatin) in the first-line treatment of participants with newly diagnosed metastatic non-squamous NSCLC. The trial consists of 3 Parts, a non-randomized Safety-run-in part (Part A) and the subsequent randomized Ph2b trial with 2 treatment arms. After the treatment of 15 participants with visugromab at the expansion dose, an interim safety and preliminary efficacy analysis will be conducted (Part B), followed by the treatment of the remaining participants (Part C).

Interventions

• Biological Visugromab
  Participants receive Visugromab (recommended dose) intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments.
• Drug Matching placebo for visugromab
  Participants receive Matching Placebo intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments.
• Biological Pembrolizumab 200 mg Q3W
  Participants receive Pembrolizumab 200 mg intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments after visugromab infusion.
• Drug Pemetrexed 500 mg/m^2
  Participants receive Pemetrexed 500 mg/m\^2 IV on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments.
• Drug Carboplatin AUC 5
  Participants receive Carboplatin target dose Area Under Curve (AUC) 5 (maximum dose 750 mg) on Day 1 of each 21-day cycle for four cycles.

Primary outcome measures

• Objective Response Rate [Time frame: up to 24 months]

Secondary outcome measures (12)

• Adverse Events [Time frame: up to 27 months]
• CR rate [Time frame: up to 24 months]
• PR rate [Time frame: up to 24 months]
• DOR [Time frame: up to 24 months]
• ORR [Time frame: up to 24 months]
• TTR [Time frame: up to 24 months]
• PFS [Time frame: up to 48 months]
• OS [Time frame: up to 48 months]
• Participant weight course over time [Time frame: up to 48 months]
• Maximum Concentration (Cmax) of visugromab [Time frame: At designated time points (up to 24 months)]
• Minimum Concentration (Cmin) of visugromab [Time frame: At designated time points (up to 24 months)]
• Participants' subjective well-being as assessed by Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) [Time frame: up to 27 months]

Eligibility criteria

Main Inclusion Criteria:

• Histologically confirmed, newly diagnosed stage IV non-squamous NSCLC.
• Demonstrated absence of actionable mutations (e.g., EGFR, ALK, among others) that suggest/require treatment with available targeted agent.
• Measurable disease determined by the local site Investigator/radiology by their assessment per RECIST v1.1.
• Have not received prior systemic treatment for advanced/metastatic NSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease and did not contain any PD 1/PD L1 directed CPI therapy.
• Availability of locally determined PD L1 TPS, determined with a test validated for this purpose, from a tumor tissue biopsy obtained after any potential prior systemic treatment for this disease. Participants with PD-L1 TPS ≥ 50% can only be enrolled in case CPI monotherapy is not clinically indicated.
• Availability of a tissue/histological biopsy for translational research investigations and Informed Consent Form (ICF) for biopsy release for translational research signed by participant. The biopsy has to be obtained after any potential prior systemic treatment for this disease and be available for shipment. A cytological sample is not accepted.
• Age ≥ 18 years on the day of signing the informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Adequate organ function (bone marrow, hepatic, renal function and coagulation).

Main Exclusion Criteria:

• Presence of predominantly squamous cell histology or predominantly neuroendocrine histology NSCLC (mixed tumors will be categorized by the predominant cell type) or presence of small cell lung cancer elements (ineligibility independent of percentage).
• Any acute or chronic major tissue injury that may require maintained GDF 15 function for tissue protection as per Investigator assessment (diagnosed with myocardial infarction, or liver, kidney or other major organ failure, all within < 3 months prior to planned treatment start).
• Major surgery (defined as a surgery which requires general anesthetic and/or involves opening of body cavities), within 4 weeks of the first dose of study drug.
• Received potentially curative radiation therapy to the lung that is > 30 Gy within 6 months prior to the first dose of study drug.
• Received or completed any focal radiotherapy for symptoms within 28 days of the first dose of study drug.
• Expected to require any other form of antineoplastic therapy while on trial.
• Clinically active inflammatory bowel disease, active diverticulitis, intra-abdominal abscess, and/or gastrointestinal obstruction.
• Known history of prior malignancy with the exception that the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
• Known or detected clinically active central nervous system (CNS) involvement by NSCLC or other tumors, e.g., with symptomatic metastases and/or carcinomatous meningitis. Participants with CNS involvement may be enrolled with mandatory regular imaging of the brain under protocol-defined conditions.
• Have one of the following cardiovascular risk factors: myocardial infarction in the past 3 months before planned treatment start; uncontrolled heart failure; uncontrolled ventricular arrhythmia; QT interval corrected for heart rate using Fridericia's formula interval ≥ 470 ms regardless of sex; peri/myocarditis in the past 3 months before planned treatment start; history of ischemic stroke in the past 3 months before planned treatment start.
• Any active autoimmune that has required systemic treatment in the past 3 months before planned treatment start (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
• Comedication with metformin or metformin-containing antidiabetics in participants with type II diabetes.
• Has interstitial lung disease or a history of non-infectious pneumonitis that required systemic steroids or current pneumonitis.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Spain · 14 centers

• University Hospital of Jaen — Jaén
• Regional University Hospital of Malaga — Málaga
• University Hospital Virgen Macarena — Seville
• University Hospital Virgen del Rocio (HUVR) — Seville
• University Hospital Marques de Valdecilla (HUMV) — Santander
• Hospital del Mar — Barcelona
• Hospital Quiron Dexeus Barcelona — Barcelona
• University Clinic of Navarra - Pamplona — Pamplona
• … and 6 more centers

United States · 7 centers

• University of Alabama at Birmingham — Birmingham
• USC Norris Comprehensive Cancer Center — Los Angeles
• Yale Cancer Center — New Haven
• Moffitt Cancer Center — Tampa
• NYU Longone Health — New York
• Duke University Medical Center — Durham
• Medical University of South Carolina — Charleston

Germany · 6 centers

• Thorax Clinic Heidelberg — Heidelberg
• University Hospital Würzburg — Würzburg
• Evangelical Hospital Bethel, Clinic for Internal Medicine, Hematology/Oncology, Palliative — Bielefeld
• Clinics Essen-Mitte — Essen
• Foundation Bethanien Moers — Moers
• Großhansdorf Hospital - Clinical Center for Pulmonology and Thoracic Surgery, Department o — Großhansdorf

Italy · 4 centers

• Institute of Romagna for Cancer Research " Dino Amadori" - IRCCS IRST — Meldola
• Oncology Reference Center — Aviano
• Local Health Unit of Romagna - Santa Maria delle Croci Hospital of Ravenna, Onco-Hematolog — Ravenna
• National Cancer Institute Regina Elena, IRCCS — Rome

Romania · 4 centers

• "Sf. Nectarie" Oncology Center, Department of Medical Oncology — Craiova
• Gral Medical S.R.L. - Oncofort Hospital — Piteşti
• Clinica Polisano S.R.L. — Sibiu
• SC Oncomed SRL, Department of Medical Oncology — Timișoara

Switzerland · 3 centers

• University Hospital Basel — Basel
• Fribourg Cantonal Hospital — Fribourg
• Cantonal Hospital Saint Gallen, Clinic of Oncology and Hematology — Sankt Gallen

Poland · 2 centers

• MED-Polonia, Sp. z o.o. (LLC) — Poznan
• Specialist Hospital in Prabuty Sp. z o.o. (LLC), Department of Pulmonology — Prabuty

Identifiers

NCT: NCT07098988 · CTL-002-003 · 2024-516792-32-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗