E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Malignant solid tumors: Patients with advanced and/or metastatic colorectal cancer (CRC), non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), renal cell carcinoma (RCC), gastric (incl. esophagogastric junction) cancer, pancreatic cancer or urothelial cancer. |
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E.1.1.1 | Medical condition in easily understood language |
advanced and/or metastatic colorectal cancer, non-small cell lung cancer, triple negative breast cancer, renal cell carcinoma, gastric cancer, pancreatic cancer, urothelial cancer. |
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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 | 10065143 |
E.1.2 | Term | Malignant solid tumour |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Dose Escalation Part: - Determine the MTD and/or the recommended Phase 2 dose (RP2D) - Establish the safety profile of GEN1029
Dose Expansion Part: - To evaluate the Objective Response Rate (ORR) by indication |
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E.2.2 | Secondary objectives of the trial |
Dose Escalation Part: - Establish the PK profile and evaluate immunogenicity of GEN1029 after single and multiple infusions - Evaluate the anti-tumor activity of GEN1029
Dose Expansion Part: - Evaluate the anti-tumor activity of GEN1029 - To further describe the safety profile of GEN1029 - Evaluate the pharmacokinetic (PK) profile as feasible, evaluate immunogenicity of GEN1029 after single and multiple infusions |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For Dose Escalation Part: Patients with advanced and/or metastatic CRC, NSCLC, TNBC, RCC, gastric (incl. esophagogastric junction), pancreas or urothelial cancer who have no available standard therapy likely to confer clinical benefit or who are not candidates for such available therapy, and for whom, in the opinion of the investigator, experimental therapy with GEN1029 may be beneficial.
For Dose Expansion Part: Patients with advanced and/or metastatic cancer in up to seven of the following indications: CRC, NSCLC, TNBC, RCC, gastric, pancreas or urothelial cancer who have failed specific anticancer therapies for metastatic disease.
- Patient must be ≥ 18 years of age - Patients must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 - Have an acceptable hematological status - Have an acceptable renal function - Have an acceptable liver function - Have an Eastern Cooperative Oncology Group performance status of 0 or 1 - Body weight ≥ 40kg - Patients, both females and males, of childbearing or reproductive potential must agree to use adequate contraception from screening visit until six months after the last infusion of IMP |
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E.4 | Principal exclusion criteria |
- Acute deep vein thrombosis or clinically relevant pulmonary embolism, not stable for at least 8 weeks prior to first IMP administration - Have clinically significant cardiac disease - Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management - Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new (younger than 6 months) or progressive brain metastases or stroke - Have received a cumulative dose of corticosteroid ≥ 150 mg prednisone (or equivalent doses of corticosteroids) within two weeks before the first IMP administration - History of ≥ grade 3 allergic reactions to monoclonal antibody therapy as well as known or suspected allergy or intolerance to any agent given in the course of this trial - Radiotherapy within 14 days prior to first IMP administration - Any prior therapy with a compound targeting DR4 or DR5 - History of chronic liver disease or evidence of hepatic cirrhosis |
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E.5 End points |
E.5.1 | Primary end point(s) |
Dose Escalation Part: - Dose limiting Toxicities (DLTs) - Adverse events (AEs) and safety laboratory parameters (hematology and biochemistry)
Dose Expansion Part: - Objective Response Rate (ORR) by indication |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
DLTs: dose limiting toxicities will be collected for the first two cycles i.e. DLT period of 28 days. AEs: screening; Day 1, 2, 3, 8 during Cycles 1-3; Days 1, 8 during subsequent Cycles (4-PD); EoT; 4, 13, 26, 39, 52 Weeks after last dosing. ORR: during the entire study |
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E.5.2 | Secondary end point(s) |
Dose Escalation Part: - PK parameters of GEN1029 - Immunogenicity of GEN1029 - Anti-tumor activity measured by tumor shrinkage - Objective Response, Progression-Free Survival (PFS), Overall Survival (OS), Duration of Response (DoR), and Time to Response (TTR)
Dose Expansion Part: - Anti-tumor activity measured by tumor shrinkage - Objective Response, Progression-Free Survival (PFS), Overall Survival (OS), Duration of Response (DoR), and Time to Response (TTR) - Adverse events (AEs) and safety laboratory parameters - PK parameters - Immunogenicity of GEN1029 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
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 | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
France |
Spain |
United Kingdom |
United States |
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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
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The trial is considered completed with the last safety follow-up visit (70 days after last dose) for the last subject participating in the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |