IMA402 T Cell-Engaging Receptor Molecule (TCER®) in Recurrent and/or Refractory Solid Tumors

Study Overview
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Brief Summary
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The goal of this clinical trial is to evaluate the safety, tolerability and anti-tumor activity of IMA402 in patients with recurrent and/or refractory solid tumors. Primary objectives: To determine the maximum tolerated dose and/or recommended dose for extension for IMA402 (Phase I) To characterize the safety and tolerability of IMA402 (Phase I/II) To evaluate anti-tumor activity of IMA402 (Phase II) Secondary objectives: To evaluate the initial anti-tumor activity of IMA402 (Phase I) To evaluate anti-tumor activity of IMA402 (Phase II) To describe the PK of IMA402 (Phase I/II)

Detailed Description
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The study will be conducted in two phases: Phase Ia: Dose escalation/de-escalation Phase Ib: Dose extension Phase II: Dose extension in selected Indication-specific extension cohort(s) (ISEC)

Official Title
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A Phase I/II First-In-Human Clinical Trial to Evaluate the Safety, Tolerability and Anti-Tumor Activity of IMA402, a Bispecific TCER® Targeting PRAME, in Patients With Recurrent and/or Refractory Solid Tumors

Conditions
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Refractory Cancer, Recurrent Cancer, Solid Tumor, Adult, Cancer

Intervention / Treatment
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* Biological: IMA402 (Phase Ia)
* Biological: IMA402 (Phase Ib)
* Biological: IMA402 (Phase II)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years old Patients must have a specific pathologically confirmed and documented advanced and/or metastatic solid tumor indication Patients must have received or not be eligible for all available indicated standard-of-care treatments Measurable disease according to RECIST 1.1 Confirmed HLA status ECOG Performance Status of 0 to 1 Adequate baseline hematologic, hepatic and renal function, acceptable coagulation status Exclusion Criteria: Other active malignancies that require treatment or that might interfere with the trial endpoints (ongoing adjuvant anti-hormonal treatment is allowed) The patient is pregnant or is breastfeeding History of hypersensitivity to components of IMA402 or rescue medications, if no alternative treatment option is available The patient has concurrent severe and/or uncontrolled medical disease. Any other health condition that would, in the investigator's judgement, contraindicate the patient's participation in the clinical trial because of safety concerns or compliance with clinical trial procedures Patients with active brain metastases

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation/de-escalation (Phase Ia)<br>Dose-Finding of IMA402 (Phase Ia) | Biological: IMA402 (Phase Ia)<br>* Intravenous infusions in escalating dose levels<br>|
| Experimental: Dose extension (Phase Ib)<br>IMA402 monotherapy extension cohorts based on maximum tolerated dose (MTD) and/or recommended doses for extensions (RDEs) (Phase Ib) | Biological: IMA402 (Phase Ib)<br>* Treatment at MTD and/or RDE (Phase Ib)<br>|
| Experimental: Dose extension (Phase II)<br>Selected ISEC investigated on MTD/RDEs based on a manageable/favorable safety profile and initial signs of anti-tumor activity (Phase II) | Biological: IMA402 (Phase II)<br>* Treatment at MTD/RDE based on a manageable/favorable safety profile and initial signs of anti-tumor activity of selected ISEC (Phase II)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Number of patients with dose limiting toxicities (DLTs) |  | 24 months | 
| Phase I/II: Number of patients with treatment-emergent adverse events (TEAEs) |  | 40 months | 
| Phase I/II: Number of patients with serious TEAEs |  | 40 months | 
| Phase I/II: Frequency of dose interruptions and reductions, permanent discontinuations |  | 40 months | 
| Phase I/II: Duration of dose interruptions and reductions, permanent discontinuations |  | 40 months | 
| Phase II: Overall response rate (ORR) based on best overall response (BOR) of complete response (CR) and partial response (PR) locally assessed using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) |  | 40 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: ORR based on BOR of CR and PR locally assessed using RECIST v1.1 and iRECIST |  | 37 months | 
| Phase II: ORR based on BOR of CR and PR locally assessed using iRECIST |  | 40 months | 
| Phase I/II: Disease control rate (DCR) of CR, PR or stable disease (SD) (lasting 6 or more weeks) following the initiation of IMA402 based on RECIST v1.1 and iRECIST |  | 40 months | 
| Phase I/II: Duration of response (DOR) of CR or PR based on RECIST v1.1 and iRECIST |  | 40 months | 
| Phase I/II: Progression-free survival (PFS) based on RECIST v1.1 and iRECIST |  | 40 months | 
| Phase I/II: Overall survival (OS) |  | 40 months | 
| Phase I/II: Determination of PK parameter: half-life (t1/2) |  | 40 months | 
| Phase I/II: Determination of PK parameter: minimal serum concentration (Cmin) |  | 40 months | 
| Phase I/II: Determination of PK parameter: maximal serum concentration (Cmax) |  | 40 months | 
| Phase I/II: Determination of PK parameter: area under the curve (AUC) |  | 40 months |