Adult Solid Tumor, Metastatic Non-Squamous Non-Small Cell Lung Cancer
Conditions
Keywords
CTL-002, Visugromab, GDF-15
Brief summary
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).
Interventions
Participants receive Visugromab (RDE) intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W)
BIOLOGICALVisugromab 6mg/kg
Participants receive Visugromab (6mg/kg) intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W)
BIOLOGICALNivolumab
Participants receive Nivolumab 360mg intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W)
Participants receive Saline intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W)
DRUGDocetaxel
Participants receive Docetaxel 75 mg/m2 intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W)
Sponsors
CatalYm GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Throughout the randomized part of the trial, participants, Investigators, trial-assigned site staff (except for the pharmacists), the CRO (except for the unblinded clinical monitoring team), and imaging vendor will remain blinded to the information of which participant is receiving which IMP in Treatment Arms A, B and D, treatment assignment to the chemotherapy-free Arm C will be open label. Sponsor staff may be unblinded on an as needed basis.
Intervention model description
Part A: Safety Run-In Part B and C: Randomized Part consists of 4 Arms: Arm A: Visugromab at the recommended dose for expansion (RDE) with Nivolumab and Docetaxel, Arm B: Visugromab 6 mg/kg with Nivolumab and Docetaxel, Arm C: Visugromab at the RDE with Nivolumab Arm D: Double Placebo (saline) and Docetaxel Participants will be allocated in 2:1:1:1 ratio to treatment arms A, B, C, or D
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | up to 36 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | up to 60 months | Incidence, type and severity of adverse events, treatment emergent adverse events, treatment-related adverse events and serious adverse events |
| CR rate | up to 36 months | Complete response rate |
| PR rate | up to 36 months | Partial response rate |
| ORR rate | up to 36 months | Overall response rate |
| DOR | up to 36 months | Duration of response |
| TTR | up to 36 months | Time-to-respond |
| PFS | up to 60 months | Progression-free survival |
| OS | up to 60 months | Overall survival |
| Participant weight course over time | up to 39 months | Participant weight course over time |
| Maximum Concentration (Cmax) of visugromab | up to 36 months | Cmax is the maximum observed serum concentration of visugromab. |
| Minimum Concentration (Cmin) visugromab | up to 36 months | Cmin is the minimum observed serum concentration of visugromab |
| Participants' subjective well-being as assessed by Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) | up to 39 months | 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 |
Countries
Germany, Italy, Poland, Romania, Spain, Switzerland, United States
Contacts
CONTACTLena Lemke, MD
STUDY_DIRECTORLena Lemke, MD
CatalYm GmbH
Outcome results
None listed