Clinical trial NCT05359445: IMA401 TCER® in Recurrent and/or Refractory Solid Tumors, Alone or in Combination With a Checkpoint Inhibitor
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Refractory Cancer
Recurrent Cancer
Solid Tumor, Adult
Cancer
Lead sponsor: Immatics Biotechnologies GmbH
Sponsor class: INDUSTRY
First posted: 2022-05-03
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with dose limiting toxicities
timeFrame: 44 months
Secondary outcomes:
measure: Number of patients with treatment-emergent adverse events (TEAEs)
timeFrame: 93 months
measure: Number of patients with serious TEAEs
timeFrame: 93 months
measure: Number of patients with treatment emergent adverse events of special interest (AESIs)
timeFrame: 93 months
measure: Frequency of dose interruptions and reductions
timeFrame: 93 months
measure: Duration of dose interruptions and reductions
timeFrame: 93 months
measure: 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
timeFrame: 93 months
measure: Disease control rate (DCR) of CR, PR or stable disease (SD) lasting 6 or more weeks following the initiation of IMA401
timeFrame: 93 months
measure: Duration of response (DOR) of CR or PR based on RECIST v1.1 and iRECIST
timeFrame: 93 months
measure: Progression-free survival (PFS) based on RECIST v1.1 and iRECIST
timeFrame: 93 months
measure: Overall survival (OS)
timeFrame: 93 months
measure: Determination of IMA 401 PK parameter: maximal serum concentration (Cmax)
timeFrame: 44 months
measure: Determination of IMA 401 PK parameter: time at Cmax (Tmax)
timeFrame: 44 months
measure: Determination of IMA 401 PK parameter: minimal serum concentration (Cmin)
timeFrame: 44 months
measure: Determination of IMA 401 PK parameter: area under the serum concentration-time curve (AUC)
timeFrame: 44 months
measure: Determination of IMA 401 PK parameter: clearance (Cl)
timeFrame: 44 months
measure: Determination of IMA 401 PK parameter: volume of distribution (Vss)
timeFrame: 44 months
measure: Determination of IMA 401 PK parameter: half-life (t1/2)
timeFrame: 44 months
measure: Determination of IMA 401 PK parameter: assessment of dose-proportionality
timeFrame: 44 months
measure: Determination of IMA 401 PK parameter: steady-state attainment
timeFrame: 44 months
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg, Zentralklinikum, Klinik fuer Innere Medizin I
state: Baden-Wurttemberg
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg AöR, Nationales Zentrum fuer Tumorkrankheiten
state: Baden-Wurttemberg
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH, Studienzentrum Thoraxonkologie
state: Baden-Wurttemberg
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen AöR, Comprehensive Cancer Center Tuebingen
state: Baden-Wurttemberg
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm AöR, ECTU-Early clinical Trials Unit Universitaetsklinikum Ulm Comprehensive Cancer Center Ulm_CCCU
state: Baden-Wurttemberg
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen AöR, Interdisciplinary Clinical Trial Unit with ECTU
state: Bavaria
city: Munich
country: Germany
facility: Klinikum rechts der Isar der TU Muenchen AöR, Klinik und Poliklinik fuer Innere Medizin III
state: Bavaria
city: Nuremberg
country: Germany
facility: Klinikum Nuernberg, Klinik fuer Innere Medizin 5, Abteilung Onkologie/Haematologie
state: Bavaria
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg AöR, Klinik fuer Innere Medizin 3
state: Bavaria
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg AöR, Interdisziplinaeres Studienzentrum mit ECTU
state: Bavaria
city: Frankfurt
country: Germany
facility: Goethe Universitaetsklinikum Frankfurt AöR, Medizinische Klinik II
state: Hesse
city: Hanover
country: Germany
facility: Medizinische Hochschule Hannover, Klinik fuer Haematologie, Haemostaseologie, Onkologie und Stammzelltransplantation
state: Lower Saxony
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn AöR, Medizinische Klinik IIII
state: North Rhine-Westphalia
city: Duesseldorf
country: Germany
facility: Marien Hospital Duesseldorf GmbH, Klinik fuer Onkologie/Haematologie und Palliativmedizin
state: North Rhine-Westphalia
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster AöR, Medizinische Klinik A
state: North Rhine-Westphalia
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR, III. Medizinische Klinik
state: Rhineland-Palatinate
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III
state: Saxony
city: Dresden
country: Germany
facility: Universitaetsklinikum C. - G. - Carus Dresden, Technische Universitaet Dresden AöR, NCT/UCC Early Clinical Trial Unit
state: Saxony
city: Leipzig
country: Germany
facility: Universitaet Leipzig, Universitaeres Krebszentrum Leipzig (UCCL)
state: Saxony
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig- Holstein, Campus Kiel, Medizinische Klinik II Haematologie und Onkologie, Karl-Lennert Tumorzentrum
state: Schleswig- Holstein
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin Berlin KöR, Klinik fuer Haematologie und Onkologie
Study officials:
affiliation: Immatics Biotechnologies GmbH
name: Immatics Biotechnologies GmbH
role: STUDY_DIRECTOR
References: