IMA401 TCER® in Recurrent and/or Refractory Solid Tumors, Alone or in Combination With a Checkpoint Inhibitor

Phase 1

Recruiting

• Conditions: Recurrent Cancer; Solid Tumor, Adult; Refractory Cancer; Cancer
• Interventions: Biological: IMA401 (Phase Ia); Biological: IMA 401 (Phase Ib); Biological: IMA401 (Phase Ib); Biological: Pembrolizumab (Phase Ia)

• Registration Number: NCT05359445
• Lead Sponsor: Immatics Biotechnologies GmbH

Brief Summary

Primary objective:

* To determine the maximum tolerated dose and/or recommended dose for extension for IMA401 as monotherapy and in combination with pembrolizumab

Secondary objectives:

* To characterize the safety and tolerability of IMA401 as monotherapy and in combination with pembrolizumab

* To evaluate initial anti-tumor activity of IMA401 as monotherapy and in combination with pembrolizumab

* To describe the pharmacokinetics of IMA401 as monotherapy and in combination with pembrolizumab

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-04-11
• Study First Submitted QC: 2022-04-28
• Study First Posted: 2022-05-03
• Study Start: 2022-05-19
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-15
• Last Update Posted: 2025-04-16
• Primary Completion: 2025-11
• Study Completion: 2029-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 95

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 NSCLC or HNSCC, other solid tumor may be considered
• Confirmed HLA status and IMA401 tumor target MAGEA4/8 expression (IMADetect®)
• Life expectancy > 2 months
• ECOG Performance Status of 0 to 1
• 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, CPI treatment or rescue medications, contraindication for pembrolizumab
• 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 active infection
• Systemic corticosteroids (≥ 10 mg/day prednisone or equivalent) received 2 weeks prior to starting trial treatment
• Patients with active brain metastases and leptomeningeal metastases

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose-Finding Escalation/De-escalation (Phase Ia) and Extension Part (Phase Ib)	IMA401 (Phase Ia)	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)
Dose-Finding Escalation/De-escalation (Phase Ia) and Extension Part (Phase Ib)	IMA401 (Phase Ib)	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)
Dose-Finding IMA401 TCER® Monotherapy (Phase Ia)	IMA401 (Phase Ia)	Dose-Finding Escalation/De-escalation with IMA401 TCER® (Phase Ia)
Dose-Finding Combination Therapy with IMA401 TCER® and Pembrolizumab (Phase Ia)	IMA401 (Phase Ia)	Dose-Finding Escalation/De-escalation of combination therapy with IMA401 TCER and pembrolizumab (Phase Ia)
Dose-Finding Combination Therapy with IMA401 TCER® and Pembrolizumab (Phase Ia)	Pembrolizumab (Phase Ia)	Dose-Finding Escalation/De-escalation of combination therapy with IMA401 TCER and pembrolizumab (Phase Ia)
Extension IMA401 TCER® Monotherapy (Phase Ib)	IMA 401 (Phase Ib)	IMA401 monotherapy extension cohort following the determination of the recommended dose for extension (RDE) (Phase Ib)

Primary Outcome Measures

Name	Time	Method
Number of patients with dose limiting toxicities	44 months

Secondary Outcome Measures

Name	Time	Method
Number of patients with treatment-emergent adverse events (TEAEs)	93 months
Number of patients with serious TEAEs	93 months
Number of patients with treatment emergent adverse events of special interest (AESIs)	93 months
Frequency of dose interruptions and reductions	93 months
Duration of dose interruptions and reductions	93 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	93 months
Disease control rate (DCR) of CR, PR or stable disease (SD) lasting 6 or more weeks following the initiation of IMA401	93 months
Duration of response (DOR) of CR or PR based on RECIST v1.1 and iRECIST	93 months
Progression-free survival (PFS) based on RECIST v1.1 and iRECIST	93 months
Overall survival (OS)	93 months
Determination of IMA 401 PK parameter: time at Cmax (Tmax)	44 months
Determination of IMA 401 PK parameter: maximal serum concentration (Cmax)	44 months
Determination of IMA 401 PK parameter: minimal serum concentration (Cmin)	44 months
Determination of IMA 401 PK parameter: area under the serum concentration-time curve (AUC)	44 months
Determination of IMA 401 PK parameter: clearance (Cl)	44 months
Determination of IMA 401 PK parameter: half-life (t1/2)	44 months
Determination of IMA 401 PK parameter: volume of distribution (Vss)	44 months
Determination of IMA 401 PK parameter: assessment of dose-proportionality	44 months
Determination of IMA 401 PK parameter: steady-state attainment	44 months

Trial Locations

Locations (21)

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR, III. Medizinische Klinik; 🇩🇪 Mainz, Rhineland-Palatinate, Germany

Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III; 🇩🇪 Chemnitz, Saxony, Germany

Universitaetsklinikum Freiburg, Zentralklinikum, Klinik fuer Innere Medizin I; 🇩🇪 Freiburg, Baden-Wurttemberg, Germany

Universitaetsklinikum Heidelberg AöR, Nationales Zentrum fuer Tumorkrankheiten; 🇩🇪 Heidelberg, Baden-Wurttemberg, Germany

Thoraxklinik Heidelberg gGmbH, Studienzentrum Thoraxonkologie; 🇩🇪 Heidelberg, Baden-Wurttemberg, Germany

Universitaetsklinikum Tuebingen AöR, Comprehensive Cancer Center Tuebingen; 🇩🇪 Tuebingen, Baden-Wurttemberg, Germany

Universitaetsklinikum C. - G. - Carus Dresden, Technische Universitaet Dresden AöR, NCT/UCC Early Clinical Trial Unit; 🇩🇪 Dresden, Saxony, Germany

Universitaet Leipzig, Universitaeres Krebszentrum Leipzig (UCCL); 🇩🇪 Leipzig, Saxony, Germany

Universitaetsklinikum Ulm AöR, ECTU-Early clinical Trials Unit Universitaetsklinikum Ulm Comprehensive Cancer Center Ulm_CCCU; 🇩🇪 Ulm, Baden-Wurttemberg, Germany

Universitaetsklinikum Erlangen AöR, Interdisciplinary Clinical Trial Unit with ECTU; 🇩🇪 Erlangen, Bavaria, Germany

Klinikum rechts der Isar der TU Muenchen AöR, Klinik und Poliklinik fuer Innere Medizin III; 🇩🇪 Munich, Bavaria, Germany

Klinikum Nuernberg, Klinik fuer Innere Medizin 5, Abteilung Onkologie/Haematologie; 🇩🇪 Nuremberg, Bavaria, Germany

Universitaetsklinikum Regensburg AöR, Klinik fuer Innere Medizin 3; 🇩🇪 Regensburg, Bavaria, Germany

Universitaetsklinikum Wuerzburg AöR, Interdisziplinaeres Studienzentrum mit ECTU; 🇩🇪 Wuerzburg, Bavaria, Germany

Goethe Universitaetsklinikum Frankfurt AöR, Medizinische Klinik II; 🇩🇪 Frankfurt, Hesse, Germany

Medizinische Hochschule Hannover, Klinik fuer Haematologie, Haemostaseologie, Onkologie und Stammzelltransplantation; 🇩🇪 Hanover, Lower Saxony, Germany

Universitätsklinikum Bonn AöR, Medizinische Klinik IIII; 🇩🇪 Bonn, North Rhine-Westphalia, Germany

Marien Hospital Duesseldorf GmbH, Klinik fuer Onkologie/Haematologie und Palliativmedizin; 🇩🇪 Duesseldorf, North Rhine-Westphalia, Germany

Universitaetsklinikum Muenster AöR, Medizinische Klinik A; 🇩🇪 Muenster, North Rhine-Westphalia, Germany

Universitaetsklinikum Schleswig- Holstein, Campus Kiel, Medizinische Klinik II Haematologie und Onkologie, Karl-Lennert Tumorzentrum; 🇩🇪 Kiel, Schleswig- Holstein, Germany

Charité Universitaetsmedizin Berlin KöR, Klinik fuer Haematologie und Onkologie; 🇩🇪 Berlin, Germany