Trial Investigating Visugromab and Nivolumab With or Without Docetaxel in 2L Treatment of Participants With Metastatic NSCLC

Ph 2, Randomized, Blinded, Placebo-Controlled Trial Investigating the Efficacy and Safety of Visugromab and Nivolumab With or Without Docetaxel Versus Docetaxel in 2L Treatment of Participants With Metastatic NSCLC (GDFATHER-NSCLC-02)

This is an exploratory, signal-finding, randomized, placebo-controlled, blinded, multi-center phase 2b trial of the anti-GDF-15 antibody Visugromab (CTL-002) at two different dose levels plus Nivolumab with Docetaxel versus Visugromab at the higher dose plus Nivolumab with placebo versus double-placebo with Docetaxel, in participants that receive second-line treatment for non-squamous NSCLC after failure of prior first-line treatment including a CPI (checkpoint inhibitor).

The trial consists of 3 Parts: an open-label Safety Run-in part (Part A) followed by a subsequent randomized phase 2b part with 4 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).

Study Overview

• Status: Recruiting
• Conditions: Adult Solid Tumor; Metastatic Non-Squamous Non-Small Cell Lung Cancer
• Intervention / Treatment: Biological: Visugromab RDE (recommended dose for expansion); Biological: Nivolumab; Drug: Docetaxel; Biological: Visugromab 6mg/kg; Other: Placebo Saline Infusion

• Study Type: Interventional
• Enrollment (Estimated): 131
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lena Lemke, MD; Phone Number: +49 89 200066440; Email: regulatory-004@catalym.com

Study Locations

• Germany
  • Baden-Wurttemberg
    • Esslingen am Neckar, Baden-Wurttemberg, Germany, 73730
      • Recruiting
      • Hospital Esslingen GmbH
      • Contact: Martin Faehling, Dr; Phone Number: +49711310382411; Email: m.faehling@klinikum-esslingen.de
      • Contact: Annika Landmesser; Phone Number: +49711310386510; Email: a.landmesser@klinikum-esslingen.de
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • Recruiting
      • University Hospital Wuerzburg, Clinic and Polyclinic II for Gastroenterology, Hematology, Internal Oncology, Stem Cell Therapies, Hepatology, Infectiology, Psychosomatics and Rheumatology/ Clinical Immunology
      • Contact: Maria- Elisabeth Goebeler, Dr; Phone Number: +49 93120140959; Email: goebeler_m@ukw.de
  • North Rhine-Westphalia
    • Bielefeld, North Rhine-Westphalia, Germany, 33611
      • Recruiting
      • Evangelical Hospital Bethel, Clinic for Internal Medicine, Hematology/Oncology, Palliative Medicine Johannesstift
      • Contact: Florian Weissinger, Prof.; Phone Number: +49 (521) 77275750; Email: florian.weissinger@evkb.de
    • Essen, North Rhine-Westphalia, Germany, 45136
      • Recruiting
      • Clinics Essen-Mitte
      • Contact: Konstantinos Ferentinos, Dr; Phone Number: +49 (201) 174-24061; Email: K.Ferentinos@kem-med.com
• Italy
  • Ravenna, Italy, 48121
    • Recruiting
    • Local Health Unit of Romagna - Santa Maria delle Croci Hospital of Ravenna, Onco-Hematology Department
    • Contact: Manolo D'Arcangelo, Dr; Phone Number: +39 0544286223; Email: manolo.darcangelo@auslromagna.it
  • Emilia-Romagna
    • Forlì, Emilia-Romagna, Italy, 47014
      • Recruiting
      • Institute of Romagna for Cancer Research "Dino Amadori" - IRCCS IRST
      • Contact: Oriana Nanni, Dr; Phone Number: +39 0543739100; Email: oriana.nanni@irst.emr.it
• Spain
  • Lugo, Spain, 27003
    • Recruiting
    • University Hospital Lucus Augusti (HULA)
    • Contact: Sergio Vázquez Estévez, Dr; Phone Number: +34 (98) 229 6028; Email: sergio.vazquez.estevez@sergas.es
  • Andalusia
    • Jaén, Andalusia, Spain, 23007
      • Recruiting
      • University Hospital of Jaen
      • Contact: Jose Lopez Lopez, Dr; Phone Number: +34 (95) 322 0306; Email: Jall92hs@gmail.com
    • Málaga, Andalusia, Spain, 29010
      • Recruiting
      • Regional University Hospital of Malaga
      • Contact: Manuel Cobo Dols, Dr; Phone Number: +34 (95) 130 8130; Email: mangel.cobo.sspa@juntadeandalucia.es
  • Madrid
    • Madrid, Madrid, Spain, 28041
      • Recruiting
      • University Hospital 12 de Octubre
      • Contact: Luis Paz-Ares Rodríguez, Dr; Phone Number: +34 (91390) 8000; Email: lpazaresr@seom.org
• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel
    • Contact: Benjamin Thiele, Dr; Phone Number: +41 (612) 655 074; Email: Benjamin.Thiele@usb.ch
  • Sankt Gallen, Switzerland, CH-9007
    • Recruiting
    • Cantonal Hospital Saint Gallen, Clinic of Oncology and Hematology
    • Contact: Markus Joerger, Dr; Phone Number: +41 (71) 494 1111; Email: markus.joerger@h-och.ch
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • Not yet recruiting
      • University of Alabama at Birmingham (O'Neal Comprehensive Cancer Center)
      • Contact: Leigh McManus, RN, MSHQS, CCRP; Phone Number: 205-934-4173; Email: lmcmanus@uabmc.edu
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Usc Norris Comprehensive Cancer Center
      • Contact: Sandy Tran; Phone Number: 323-865-3935; Email: Sandy.Tran@med.usc.edu
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Not yet recruiting
      • Duke University Medical Center
      • Contact: Alicia Wilkerson; Phone Number: 919-681-4768; Email: Alicia.wilkerson@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

• Participants must have histologically or cytologically confirmed diagnosis of stage IV non-squamous NSCLC.
• Participants must have demonstrated absence of actionable mutations (e.g. EGFR, ALK, among others) that suggest/require treatment with available targeted agent.
• Participants must have failed one line of prior systemic treatment for metastatic NSCLC containing an approved anti PD (L)1 checkpoint inhibitor (CPI). The minimum treatment duration on this regimen must have been 12 weeks exposure for the CPI with no documented progression in this period. Failure of the prior line of systemic treatment for metastatic NSCLC must have occurred under ongoing CPI treatment. Discontinuation of the prior CPI and line of treatment due to AEs, or any other reason than progression/relapse does not permit enrollment.
• Participants must have measurable disease determined by the local site Investigator by their assessment per RECIST v1.1.
• Participants must have life expectancy of at least 3 months as assessed by the Investigator.
• Participants must have ECOG performance status ≤1.

Main Exclusion Criteria:

• Participants must not have received more than one line of prior systemic treatment for advanced/metastatic NSCLC.
• Participants must not have a prior malignancy requiring treatment.
• Participants must not have a 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 must not have any active autoimmune disease that has required systemic treatment in past 3 months before planned treatment start (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
• Participants must not have interstitial lung disease or a history of (non-infectious) pneumonitis that required systemic steroids or current pneumonitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Visugromab (RDE) + Nivolumab (360 mg) + Docetaxel (75 mg/m2), intravenous (IV) on Day 1 of every 21-day cycle every 3 weeks (Q3W)	Biological: Visugromab RDE (recommended dose for expansion); Participants receive Visugromab (RDE) intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W); Other Names: CTL-002; Biological: Nivolumab; Participants receive Nivolumab 360mg intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W); Other Names: OPDIVO®; Drug: Docetaxel; Participants receive Docetaxel 75 mg/m2 intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W)
Experimental: Arm B; Visugromab (6mg/kg) + Nivolumab (360 mg) + Docetaxel (75 mg/m2), intravenous (IV) on Day 1 of every 21-day cycle every 3 weeks (Q3W)	Biological: Nivolumab; Participants receive Nivolumab 360mg intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W); Other Names: OPDIVO®; Drug: Docetaxel; Participants receive Docetaxel 75 mg/m2 intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W); Biological: Visugromab 6mg/kg; Participants receive Visugromab (6mg/kg) intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W); Other Names: CTL-002
Experimental: Arm C; Visugromab (RDE) + Nivolumab (360 mg) + Placebo (Saline) intravenous (IV) on Day 1 of every 21-day cycle every 3 weeks (Q3W)	Biological: Visugromab RDE (recommended dose for expansion); Participants receive Visugromab (RDE) intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W); Other Names: CTL-002; Biological: Nivolumab; Participants receive Nivolumab 360mg intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W); Other Names: OPDIVO®
Active Comparator: Arm D; Double Placebo (Saline) + Docetaxel (75 mg/m2), intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W)	Drug: Docetaxel; Participants receive Docetaxel 75 mg/m2 intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W); Other: Placebo Saline Infusion; Participants receive Saline intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W); Other Names: 0.9% NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the Investigator at any time during the core trial period	up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Incidence, type and severity of adverse events, treatment emergent adverse events, treatment-related adverse events and serious adverse events	up to 60 months
CR rate	Complete response rate	up to 36 months
PR rate	Partial response rate	up to 36 months
ORR rate	Overall response rate	up to 36 months
DOR	Duration of response	up to 36 months
TTR	Time-to-respond	up to 36 months
PFS	Progression-free survival	up to 60 months
OS	Overall survival	up to 60 months
Participant weight course over time	Participant weight course over time	up to 39 months
Maximum Concentration (Cmax) of visugromab	Cmax is the maximum observed serum concentration of visugromab.	up to 36 months
Minimum Concentration (Cmin) visugromab	Cmin is the minimum observed serum concentration of visugromab	up to 36 months
Participants' subjective well-being as assessed by Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ)	NSCLC-SAQ is a participant reported outcome with seven (7) items assessing five (5) symptom domains of NSCLC: cough, fatigue, pain, dyspnea, and appetite. Each item is scored individually from 0 ("None/Never") to 4 ("Severe/Always"). The total score is calculated by summing domain scores, which are derived as follows: single-item domains (cough, dyspnea, appetite) use the item score; fatigue uses the mean of two items (or one if only one is answered); pain uses the highest score of two items (or one if only one is answered). The total score ranges from 0-20, with higher scores indicating more severe symptoms. If any domain score is missing, a total score is not computed	up to 39 months

Collaborators and Investigators

• Sponsor: CatalYm GmbH
• Investigators: Study Director: Lena Lemke, MD, CatalYm GmbH

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2025
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2031

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: November 19, 2025
• First Posted (Actual): November 24, 2025

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: CTL-002; GDF-15; Visugromab
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Pharmaceutical Preparations; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Diterpenes; Crystalloid Solutions; Isotonic Solutions; Solutions; Docetaxel; Nivolumab; Saline Solution
• Other Study ID Numbers: CTL-002-004; 2024-516794-70-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No