Phase 1/2 FIH trial of CTL-002 in subjects with advanced-stage, relapsed/refractory solid tumors.
- Conditions
- 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: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-002103-19-DE
- Lead Sponsor
- CatalYm GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 238
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
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 < 6 months prior to Screening).
6. Pre-existing arrhythmia (unless considered clinically not relevant), uncontrolled angina pectoris, diagnosed with heart failure New York Heart Association (NYHA) Grade IV, any myocardial infarction/coronary event as well as any central nervous system (CNS)-ischemic event and any thromboembolic event at any time < 6 months prior to Screening or presence of uncontrolled heart failure NYHA Grade III or higher
7. Left ventricular ejection fraction (LVEF) < 50% as measured by an echocardiogram (ECHO) or multigated acquisition (MUGA) scan if ECHO cannot be performed at site for any reason
8. QT interval corrected for heart rate using Fridericia’s formula (QTcF) interval > 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 < 6 months prior to Screening.
11. Any active inflammatory bowel disease such as Crohn’s disease or ulcerative colitis which are generally excluded or active autoimmunthyroiditis present < 6 months prior to Screening.
12. Type I diabetes.
13. History of CNS disease such as stroke, seizure, encephalitis, or multiple sclerosis (< 6 months prior to Screening).
14. Any history of motor neuron disorder or disease that affects motor neuron function.
15. Ongoing immune-related AEs (irAEs) and/or AEs = Grade 2 not resolved from previous therapies except vitiligo, stable peripheral sensory neuropathy up to Grade 2, hair loss, and stable endocrinopathies with substitutive hormone therapy.
16. Active allergy requiring systemic treatment (with the exception of histamine H1 receptor blocker treatment) or active infections requiring systemic anti-infectious therapy.
17. History of or clinical evidence of CNS primary tumors or metastases including leptomeningeal metastases, unless they have been previously treated, demonstrated no progression at least for 3 months before Screening, are asymptomatic and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days before Screening – subjects with suspected brain metastases at Screening should undergo a CT/MRI of the brain prior to study entry.
18. Systemic steroids at a daily dose of > 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method