Advance-stage, relapsed/refractory solid tumors in non-curable state, that relapsed post or were refractory to a prior anti-PD-1/PD-L1 therapy. MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: CTL-002
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: -
Other descriptive name: CTL-002
Concentration unit: mg/ml milligram(s)/millilitre
Conc
Sponsors
CatalYm GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Screening: 1.Provide signed and dated informed consent. For Part A only: signed pre-screening consent for patients that undergo pre-screening procedures 2. Male or female aged = 18 years. 3.Subjects with histologically or cytologically confirmed/documented diagnosis of advanced-stage, relapsed/refractory solid tumors in non-curable state as per current clinical knowledge who have exhausted all available approved standard treatments or are not eligible for them anymore. 4. For Part A (Ph 1), subjects must have received during their prior treatment at least one anti-PD-1/PD-L1 treatment (alone or in combination) and progressed on or relapsed after completion of the anti-PD-1/PD-L1 treatment (with a minimum of 12 weeks of anti-PD1/PD-L1 exposure). For Part B (Ph 2a), subjects must either have (1) bladder CA, hepatocellular CA, non-small cell lung cancer, or melanoma (for melanoma, only cutaneous and mucosal forms, not uveal/ocular) (approved anti-PD-1/PD-L1 indications) that relapsed on or were primary refractory to prior anti-PD-1/PD-L1 therapy with an approved anti-PD-1/PD-L1 compound (with a minimum of 12 weeks of anti-PD-1/PD-L1 exposure), and have exhausted all available approved standard treatments or are not eligible for them anymore (2) CRC (MSS/mismatch-repair competent) and have not received any prior anti-PD-1/PD-L1 therapy. (Note: Not applicable in Germany), or (3) biomarker cohort with mixed solid tumors (”basket” cohort;) that relapsed or were primary refractory to prior anti PD-1/PD-L1 therapy with an approved anti-PD-1/PD-L1 compound and have exhausted all available approved standard treatments or are not eligible for them anymore. Note: All Subjects in cohorts (1) and (3) must have received an approved anti-PD-1/PD-L1 compound with a minimum of 12 weeks of anti-PD1/PD L1 exposure. Non-approved, experimental anti-PD-1/PD-L1 treatments are not permissive for enrolment into this group. 5.Ability to understand the purpose of the study, provide signed and dated informed consent prior to performing any protocol-related procedures (including Screening evaluations) 6. For Part A, ideally ~50% of subjects enrolled per dose level should have increased GDF-15 serum levels [based on pre-screening result or historic serum GDF-15 data (up to 2 months prior to the start of treatment with CTL-002 where available)]. 7.All subjects must have biopsy-accessible tumor lesions and be willing to undergo tumor biopsy: triple-sequential biopsies (Part A) or dual-sequential biopsies (Part A backfill); in Part B, baseline biopsy (new or archived if obtained within 120 days prior to treatment start) from all subjects. In the melanoma, and the biomarker cohort with mixed solid tumors (“basket” cohort), an additional on-treatment biopsy is mandatory. All biopsies are mandatory unless not seen as safe and feasible by the treating physician or another specific reason that precludes a biopsy sample being taken and which should be discussed with the Medical Monitor prior to Screening or if applying to the sequential biopsy, prior to that biopsy. All other study eligibility criteria must be met before the baseline biopsy sample is obtained. (Important note for the biomarker cohort: in case biopsy cannot be taken for medical reasons and no archived biopsy <120 days is available, subject cannot be included. 8. For Part B, presence of radiologically measurable disease at baseline – with at least 1 lesion, not previously irradiated, that can be accurately
Exclusion criteria
Exclusion criteria: 1. Pregnant or breastfeeding. 2. Has received any tumor-directed therapy within 21 days before start of study treatment. 3. Treatment with any investigational agent within 21 days before start of study treatment. 4. Radiotherapy within 14 days before the start of the study treatment; however, subjects may receive palliative radiotherapy upon discussion and approval from the Medical Monitor if needed on non-target lesions. 5. Any acute or chronic major tissue injury that may require maintained GDF-15 function for tissue protection as per Investigator assessment (diagnosed with liver, kidney, myocardial infarction, or other major organ failure, all within 450 ms for men or > 470 ms for women. 9. Any active autoimmune disease that requires systemic immunosuppressive treatments, for which (re-)activation may present a medical threat to the subject as per Investigator’s assessment 10. Any history of non-infectious pneumonitis 10 mg of prednisolone, > 2 mg of dexamethasone or equivalent, except non-systemic (inhaled, topical, nasal), for the last 28 days and ongoing. 19. Subjects with rapidly progressing disease (as per Investigator assessment), which may predispose to inability to tolerate treatment and/or study procedure. 20. Major surgery within last 4 weeks prior to Screening. 21. Known/expected hypersensitivity against CTL-002 and/or anti-PD-1/PD-L1 agents or their ingredients or previously had
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Part B: To explore the preliminary anti-tumor activity of CTL-002 administered in combination with an anti-PD-1 checkpoint inhibitor in in subjects with advanced-stage relapsed/refractory solid tumors in non-curable state as per current clinical knowledge that have either (1) bladder CA, hepatocellular CA, non-small cell lung cancer or melanoma (for melanoma, only cutaneous and mucosal forms, not uveal/ocular) (approved anti-PD-1/PD-L1 indications) that relapsed on or were primary refractory to prior anti-PD-1/PD-L1 therapy with an approved anti-PD-1/PD-L1 compound and have exhausted all available approved standard treatments or are not eligible for them anymore, or (2) CRC (micro-satellite stable [MSS]/mismatch-repair competent) and have not received any prior anti-PD-1/PD-L1 therapy, or (3) biomarker cohort with mixed solid tumors that relapsed or were primary, anti-PD-1/PD-L1 therapy Note: The colorectal cancer cohort is not applicable for Germany. ;Secondary Objective: PART A: - To explore the pharmacokinetics (PK) of CTL-002 administered as monotherapy and in combination with an anti-PD-1 checkpoint inhibitor. - To explore the pharmacodynamics of CTL-002 administered as monotherapy and in combination with an anti-PD-1 checkpoint inhibitor. - To determine the recommended dose(s) for the expansion cohorts (Part B [expansion]) of CTL-002 administered as monotherapy and in combination with an anti-PD-1 checkpoint inhibitor. - To explore the preliminary anti-tumor activity of CTL-002 administered in combination with an anti-PD-1 checkpoint inhibitor. - To explore the effect of CTL-002 on prevention of anorexia and muscle wasting (cachexia). PART B: - To confirm and further explore the PK/pharmacodynamics of CTL-002 given in combination with an anti-PD-1 checkpoint inhibitor. - To confirm the recommended Phase 2 dose (RP2D) of CTL-002. ;Timepoint(s) of evaluation of this end point: Please refer to Schedule of Assessments;Primary end point(s): PART | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PART A: - Evaluation of PK parameters of CTL-002 (e.g., maximum concentration [Cmax], area under the curve [AUC], and half-life [t1/2]). - Evaluation of treatment-emergent cytokine profiles in peripheral blood. - Evaluation of treatment-induced anti-drug antibodies (ADA). - Evaluation of the clinical efficacy according to Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 of CTL-002 as monotherapy and in combination with an anti-PD-1 checkpoint inhibitor by assessment of: o The proportion of subjects with tumor shrinkage, a confirmed partial response (PR) and/or complete response (CR), and overall response rate (ORR). o The interval between the date of first CTL-002 administration and first documented evidence of a PR or CR (Time to Response [TTR]). o The interval between the date of first documented evidence of PR or CR, until first documented evidence of disease progression or death, due to any cause (Duration of Response [DOR]). o The interval between the date of first CTL-002 administration and the earliest date of disease progression or death (Progression Free Survival [PFS]). o The interval between the date of first CTL-002 administration and date of death due to any cause (Overall Survival [OS]). - To assess appetite, body mass index (BMI), and muscle mass (e.g., L3 skeletal muscle index [L3SMI]). PART B: Secondary Endpoints: - Evaluation of PK parameters of CTL-002 (e.g., Cmax, AUC and t1/2). - Evaluation of treatment-emergent cytokine and chemokine profiles in peripheral blood. - Evaluation of treatment-induced ADA. - Evaluation of GDF-15 baseline serum levels and their correlation with pharmacodynamics and clinical response. ;Timepoint(s) of evaluation of this end point: Please refer to Schedule of Assessments | — |
Countries
Germany, Italy, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactPetra Fettes
CatalYm GmbH
Outcome results
None listed