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

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®), as Monotherapy or in Combination With Checkpoint Inhibitor in Patients With Recurrent and/or Refractory Solid Tumors.

The goal of this clinical trial is to evaluate the safety, tolerability and initial anti-tumor activity of IMA401 as monotherapy or in combination with checkpoint inhibitor in patients with recurrent and/or refractory solid tumors.

Patients' HLA status and expression of the MAGE-A4 and/or MAGE-A8 target in the tumor must be confirmed.

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

Study Overview

• Status: Active, not recruiting
• Conditions: Cancer; Solid Tumor, Adult; Refractory Cancer; Recurrent Cancer
• Intervention / Treatment: Biological: IMA401 (Phase Ia); Biological: Pembrolizumab (Phase Ia); Biological: IMA 401 (Phase Ib)

• Study Type: Interventional
• Enrollment (Estimated): 95
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12203
    • Charité Universitaetsmedizin Berlin KöR, Klinik fuer Haematologie und Onkologie
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • Universitaetsklinikum Freiburg, Zentralklinikum, Klinik fuer Innere Medizin I
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • Universitaetsklinikum Heidelberg AöR, Nationales Zentrum fuer Tumorkrankheiten
    • Heidelberg, Baden-Wurttemberg, Germany, 69126
      • Thoraxklinik Heidelberg gGmbH, Studienzentrum Thoraxonkologie
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Universitaetsklinikum Tuebingen AöR, Comprehensive Cancer Center Tuebingen
    • Ulm, Baden-Wurttemberg, Germany, 89081
      • Universitaetsklinikum Ulm AöR, ECTU-Early clinical Trials Unit Universitaetsklinikum Ulm Comprehensive Cancer Center Ulm_CCCU
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Universitaetsklinikum Erlangen AöR, Interdisciplinary Clinical Trial Unit with ECTU
    • Munich, Bavaria, Germany, 81675
      • Klinikum rechts der Isar der TU Muenchen AöR, Klinik und Poliklinik fuer Innere Medizin III
    • Nuremberg, Bavaria, Germany, 90419
      • Klinikum Nuernberg, Klinik fuer Innere Medizin 5, Abteilung Onkologie/Haematologie
    • Regensburg, Bavaria, Germany, 93053
      • Universitaetsklinikum Regensburg AöR, Klinik fuer Innere Medizin 3
    • Würzburg, Bavaria, Germany, 97078
      • Universitaetsklinikum Wuerzburg AöR, Interdisziplinaeres Studienzentrum mit ECTU
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
      • Goethe Universitaetsklinikum Frankfurt AöR, Medizinische Klinik II
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Medizinische Hochschule Hannover, Klinik fuer Haematologie, Haemostaseologie, Onkologie und Stammzelltransplantation
  • North Rhine-Westphalia
    • Bonn, North Rhine-Westphalia, Germany, 53127
      • Universitätsklinikum Bonn AöR, Medizinische Klinik IIII
    • Düsseldorf, North Rhine-Westphalia, Germany, 40479
      • Marien Hospital Duesseldorf GmbH, Klinik fuer Onkologie/Haematologie und Palliativmedizin
    • Münster, North Rhine-Westphalia, Germany, 48149
      • Universitaetsklinikum Muenster AöR, Medizinische Klinik A
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55131
      • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR, III. Medizinische Klinik
  • Saxony
    • Chemnitz, Saxony, Germany, 09116
      • Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III
    • Dresden, Saxony, Germany, 01307
      • Universitaetsklinikum C. - G. - Carus Dresden, Technische Universitaet Dresden AöR, NCT/UCC Early Clinical Trial Unit
    • Leipzig, Saxony, Germany, 04103
      • Universitaet Leipzig, Universitaeres Krebszentrum Leipzig (UCCL)
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Universitaetsklinikum Schleswig- Holstein, Campus Kiel, Medizinische Klinik II Haematologie und Onkologie, Karl-Lennert Tumorzentrum

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 MAGE-A4 and/or MAGE-A8 expression
• 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 central nervous system metastases and leptomeningeal metastases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose-Finding IMA401 TCER® Monotherapy (Phase Ia); Dose-Finding Escalation/De-escalation with IMA401 TCER® (Phase Ia)	Biological: IMA401 (Phase Ia); Intravenous infusions in escalating dose levels
Experimental: Dose-Finding Combination Therapy with IMA401 TCER® and Pembrolizumab (Phase Ia); Dose-Finding Escalation/De-escalation of combination therapy with IMA401 TCER and pembrolizumab (Phase Ia)	Biological: IMA401 (Phase Ia); Intravenous infusions in escalating dose levels; Biological: Pembrolizumab (Phase Ia); Intravenous infusions in escalating dose levels for combination of IMA 401 and Pembrolizumab; Other Names: Keytruda®
Experimental: Extension IMA401 TCER® Monotherapy (Phase Ib); IMA401 monotherapy extension cohort following the determination of the recommended dose for extension (RDE) (Phase Ib)	Biological: IMA 401 (Phase Ib); Treatment at recommended dose for extension (RDE)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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: maximal serum concentration (Cmax)	44 months
Determination of IMA 401 PK parameter: time at Cmax (Tmax)	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: volume of distribution (Vss)	44 months
Determination of IMA 401 PK parameter: half-life (t1/2)	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

Collaborators and Investigators

• Sponsor: Immatics Biotechnologies GmbH
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Director: Immatics Biotechnologies GmbH, Immatics Biotechnologies GmbH

Publications and helpful links

Helpful Links

• Corporate Website

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2022
• Primary Completion (Actual): March 18, 2026
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: April 11, 2022
• First Submitted That Met QC Criteria: April 28, 2022
• First Posted (Actual): May 3, 2022

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: MAGE-A4
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Neoplasms; Recurrence; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: IMA401-101; 2023-506854-19-00 (Other Identifier: Clinical Trials Information System)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan to make IPD available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No