| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Recurrent and / or refractory solid tumors |
| Rezidivierende und /oder refraktäre solide Tumoren |
|
| E.1.1.1 | Medical condition in easily understood language |
| Solid Tumors |
| Solide Tumoren |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10065252 |
| E.1.2 | Term | Solid tumor |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Phase 1:
- To evaluate safety and tolerability of treatment with ACTengine® IMA203/IMA203CD8 products as monotherapy or in combination with nivolumab
- To determine the maximum tolerated dose (MTD) and/or recommended dose for extension (RP2D) for IMA203/IMA203CD8
Phase 2:
- To evaluate safety and tolerability of treatment with ACTengine® IMA203 product as monotherapy
- To evaluate the initial anti-tumor activity of IMA203 |
Phase 1:
- Evaluierung der Sicherheit und Verträglichkeit der Behandlung mit ACTengine® IMA203/IMA203CD8 Produkten als Monotherapie oder in Kombination mit Nivolumab
- Bestimmung der maximal tolerierten Dosis (MTD) und/oder der empfohlenen Phase 2-Dosierung für IMA203/IMA203CD8
Phase 2:
- Evaluierung der Sicherheit und Verträglichkeit der Behandlung mit ACTengine® IMA203 Produkt als Monotherapie
- Evaluierung der initialen Antitumoraktivität von IMA203
|
|
| E.2.2 | Secondary objectives of the trial |
Phase 1:
- To evaluate persistence of TCR-engineered T cells after monotherapy or in combination with nivolumab
- To evaluate anti-tumor activity after monotherapy or in combination with nivolumab
Phase 2:
- To evaluate the initial anti-tumor activity of IMA203
- To evaluate persistence of TCR engineered T cells after monotherapy |
Phase 1:
- Evaluierung der Persistenz TCR-modifizierter T-Zellen nach Monotherapie oder in Kombination mit Nivolumab
- Evaluierung der Antitumoraktivität nach Monotherapie oder in Kombination mit Nivolumab
Phase 2:
- Evaluierung der initialen Antitumoraktivität von IMA203
- Evaluierung der Persistenz von TCR modifizierter T-Zellen nach Monotherapie
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Eligibility Criteria: Initial Screening (HLA Screening, Biomarker Screening, and Leukapheresis):
1. Patient must have voluntarily signed a written ICF1
2. Patient must have pathologically confirmed advanced and/or metastatic solid tumor.
3. Patients ≥ 18 years of age
4. ECOG PS 0 to 1
5. HLA phenotype: HLA-A*02:01 positive
6. The patient has adequate pulmonary function.
7. The patient has adequate organ and marrow function
8. Acceptable coagulation status
9. The patient has adequate hepatic and renal function
10. For leukapheresis eligibility, patient’s tumor must express IMA203/IMA203CD8-specific tumor biomarker
11. For HCC patients: an upper endoscopy is required
Eligibility Criteria: Treatment Screening (Prior to Lymphodepletion and IMA202 Infusion):
1. Patient must have voluntarily signed a written ICF2
2. Life expectancy > 3 months
3. ECOG PS 0 to 1
4. The patient has adequate hepatic function
5. The patient must have adequate renal function
6. Patients must have measurable disease according to RECIST 1.1
7. Confirmed and adequate production timelines and capacities
8. 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.
9. For HCC patients only: Child Pugh score ≤ 6
10. Female patients of childbearing potential must use adequate contraception
11. Male patients must agree to use effective contraception
12. The patient must have recovered from any side effects of prior therapy
Extension cohort B Eligibility Criteria: Nivolumab Treatment:
1. Patients have adequately recovered organ and marrow function
Note: Eligibility for combination treatment may be assessed at Day 14 or Day 21.
2. Patients must have recovered from infections to Grade 1 or lower |
|
| E.4 | Principal exclusion criteria |
Eligibility Criteria: Initial Screening (HLA Screening, Biomarker Screening, and Leukapheresis):
1. History of other malignancies
2. Solid tumors indications with low target prevalence as indicated by the sponsor
3. The patient is pregnant or is breastfeeding
4. Patients with prior allogenic stem cell transplantation or solid organ transplantation
5. History of hypersensitivity to CY, FLU or IL-2 and Rescue medication
6. The patient has received systemic corticosteroids within 2 weeks prior to leukapheresis. The patient has received other anti-tumor therapies.
7. The patient has concurrent severe and/or uncontrolled medical disease
8. Any other condition that would, in the investigator’s or sponsor’s judgment, contraindicate the patient’s participation in the clinical study
9. Patient with any active infection (e.g., COVID-19, influenza, SARS)
Eligibility Criteria: Treatment Screening (Prior to Lymphodepletion and IMA203 Infusion):
1. Patients with active brain metastases
2. The patient has received any anti-tumor therapy chemotherapy, radiotherapy, or investigational therapies within 1 week prior to
lymphodepletion; Patients must have completed any major surgery at least 4 weeks prior to lymphodepletion
3. Patient, in the judgment of the investigator, is not able to tolerate lymphodepletion, low dose IL-2, and/or IMA203/IMA203CD8 treatment
4. The patient is pregnant or is breastfeeding
5. The patient has concurrent severe and/or uncontrolled medical disease
6. Patient with any active infection (e.g., COVID-19, influenza, SARS)
7. Concurrent treatment in an another clinical trial or a device study that could interfere with the IMA203/IMA203CD8 treatment after signature of ICF2.
8. Any condition that would, in the investigator’s or sponsor’s judgment, contraindicate the patient’s participation in the clinical study because of safety concerns or compliance with clinical study procedures
Extension cohort B Eligibility Criteria: Nivolumab Treatment:
1. Patients with a history of severe immune-related toxicities, defined as any Grade 3 or 4 toxicities related to prior PD1/PD-L1 inhibitor therapy (e.g., atezolizumab, pembrolizumab or nivolumab etc.).
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Phase 1:
- Treatment-emergent adverse events (TEAEs)
- Adverse Events of special interest (AESIs)
- Treatment - emergent serious adverse events (TESAE)
- Number of patients with dose-limiting toxicities (DLTs)
Phase 2:
Treatment-emergent adverse events (TEAEs)
- Adverse Events of special interest (AESIs)
- Treatment - emergent serious adverse events (TESAE)
- Objective response rate (ORR) based on best overall response (BOR) of complete response (CR) and partial response (PR) locally assessed using RECIST 1.1
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase1:
Safety: continuous full safety surveillance between S2 and EoV visit.
Limited safety surveillance between S1 and S2 and during the follow-up starting after EoV Visit
DLT: 2 days starting at day 0
Phase 2:
Safety: continuous full safety surveillance between S2 and EoV visit.
Limited safety surveillance between S1 and S2 and during the follow-up starting after EoV Visit
CT scan on day 42 and additional confirmation CT/MRI scan 4 to 6 weeks after initial assessment of CR or PR.
|
|
| E.5.2 | Secondary end point(s) |
Phase 1:
- In vivo IMA203/IMA203CD8 T-cell persistence in the peripheral of blood
- Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and additionally by immune-related RECIST (irRECIST)
- Duration of response (DOR)
Phase 2:
• ORR based on BOR of CR and PR locally assessed using irRECIST
• Disease control rate (DCR) of CR, PR or stable disease (SD) lasting 6 or more weeks following the infusion of IMA203 locally assessed using RECIST v1.1 and irRECIST
• DOR of CR or PR based on locally assessed RECIST v1.1 and irRECIST
• Progression-free survival (PFS)
• Overall survival (OS)
• In vivo IMA203 T-cell persistence in the peripheral blood
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Phase 1:
PBMC is taken at the visits continuously from VB until LV (including Follow up)
CT scans at VB, Day 42, V9, V10, V11, LV/V12
Duration of response: until V12
Phase 2:
CT scan on day 42 and additional confirmation CT/MRI scan 4 to 6 weeks after initial assessment of CR or PR.
PFS and OS End of Follow up phase
In vivo IMA203 T-cell persistence continuously till End of Follow up phase |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 8 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 8 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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