IMA401 TCER® in Recurrent and/or Refractory Solid Tumors

Study Overview
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Brief Summary
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Primary objective: To determine the maximum tolerated dose and/or recommended dose for extension for IMA401 Secondary objectives: To characterize the safety and tolerability of IMA401 To evaluate initial anti-tumor activity of IMA401 To describe the pharmacokinetics of IMA401

Official Title
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A Phase Ia/Ib First-In-Human Clinical Trial to Evaluate the Safety, Tolerability and Initial Anti-tumor Activity of IMA401, a Bispecific T Cell Engaging Receptor Molecule (TCER®), in Patients With Recurrent and/or Refractory Solid Tumors.

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

Intervention / Treatment
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* Biological: IMA401 (Phase Ia)
* Biological: IMA401 (Phase Ib)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have voluntarily signed a written ICF, be able to understand and comply with clinical trial procedures Patients ≥ 18 years old Patients must have pathologically confirmed and documented advanced and/or metastatic solid tumor Confirmed HLA status and IMA401 tumor target MAGEA4/8 expression (IMADetect®) Life expectancy > 2 months ECOG Performance Status of 0 to 2 Measurable disease according to RECIST 1.1 Adequate baseline hematologic, renal and hepatic function; acceptable coagulation status Patients must have recurrent and/or refractory solid tumors and must have received or not be eligible for all available indicated standard of care treatments The patient must have recovered from any side effects of prior therapy to Grade 1 or lower (except for non-clinically significant toxicities; e.g., alopecia, vitiligo) prior to treatment start. As determined by the investigator, the patient may still be eligible if the patient has not fully recovered from Grade ≥ 2 toxicities, in case if these toxicities are not anticipated to further improve (e.g., chronic peripheral neuropathy) and such toxicities are not anticipated to worsen with the IMA401 therapy Exclusion Criteria: Other active malignancies that require treatment or that might interfere with the trial endpoints (ongoing adjuvant anti-hormonal treatment is allowed) History of hypersensitivity to components of IMA401 or rescue medications, if no alternative treatment option is available Patients with prior allogeneic stem cell transplantation or organ transplantation Patients with autoimmune diseases needing disease-directed treatment Any serious or uncontrolled health condition, which, in the opinion of the Investigator, would place the subject at undue risk from the study, impair the ability of the subject to receive protocol specified therapy, or interfere with the interpretation of study results Positive for HIV or with active hepatitis B or C infection. Patients with any clinically relevant, active infection Systemic corticosteroids (≥ 10 mg/day prednisone or equivalent) received 2 weeks prior to starting IMA401 therapy 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose-Finding Escalation/De-escalation (Phase Ia) and Extension Part (Phase Ib)<br>Dose-Finding Escalation/De-escalation of IMA401 (Phase Ia) IMA401 monotherapy extension cohort following the determination of the recommended dose for extension (RDE) (Phase Ib) | Biological: IMA401 (Phase Ia)<br>* Intravenous infusions in escalating dose levels<br>Biological: IMA401 (Phase Ib)<br>* Treatment at recommended dose for extension (RDE)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with dose limiting toxicities |  | 44 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with treatment-emergent adverse events (TEAEs) |  | 68 months | 
| Number of patients with serious TEAEs |  | 68 months | 
| Number of patients with treatment emergent adverse events of special interest (AESIs) |  | 68 months | 
| Frequency of dose interruptions and reductions |  | 68 months | 
| Duration of dose interruptions and reductions |  | 68 months | 
| Overall response rate (ORR) based on best overall response (BOR) of complete response (CR) and partial response (PR) locally assessed using RECIST v1.1 and iRECIST |  | 68 months | 
| Disease control rate (DCR) of CR, PR or stable disease (SD) lasting 6 or more weeks following the initiation of IMA401 |  | 68 months | 
| Duration of response (DOR) of CR or PR based on RECIST v1.1 and iRECIST |  | 68 months | 
| Progression-free survival (PFS) based on RECIST v1.1 and iRECIST |  | 68 months | 
| Overall survival (OS) |  | 68 months | 
| Determination of PK parameter: maximal serum concentration (Cmax) |  | 44 months | 
| Determination of PK parameter: time at Cmax (Tmax) |  | 44 months | 
| Determination of PK parameter: minimal serum concentration (Cmin) |  | 44 months | 
| Determination of PK parameter: area under the serum concentration-time curve (AUC) |  | 44 months | 
| Determination of PK parameter: clearance (Cl) |  | 44 months | 
| Determination of PK parameter: volume of distribution (Vss) |  | 44 months | 
| Determination of PK parameter: half-life (t1/2) |  | 44 months | 
| Determination of PK parameter: assessment of dose-proportionality |  | 44 months | 
| Determination of PK parameter: steady-state attainment |  | 44 months |