E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Malignant solid tumors:
Patients with relapsed or refractory, advanced and/or metastatic non-small cell lung cancer (NSCLC), endometrial carcinoma (EC), urothelial carcinoma (UC), triple-negative breast cancer (TNBC), squamous cell carcinoma of the head and neck (SCCHN), or cervical cancer who are not anymore candidates for or refuse standard therapy |
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E.1.1.1 | Medical condition in easily understood language |
advanced and/or metastatic non-small cell lung cancer, endometrial carcinoma, urothelial carcinoma, triple-negative breast cancer, squamous cell carcinoma of the head and neck, or cervical 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 |
- Determine the MTD and/or the recommended Phase 2 dose (RP2D) - Establish the safety profile of GEN1046 |
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E.2.2 | Secondary objectives of the trial |
- Establish the PK profile - Evaluate immunogenicity of GEN1046 - Evaluate the anti-tumor activity of GEN1046 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For Dose Escalation: • Measurable disease according to RECIST 1.1. • Eastern Cooperative Oncology Group (ECOG) 0-1. • Adequate hematologic, coagulation, hepatic and renal function as defined per protocol. • Subjects must have a histologically or cytologically confirmed non-CNS solid tumor that is metastatic or unresectable and for whom there is no available standard therapy.
For Dose Expansion: • Measurable disease according to RECIST 1.1. • Eastern Cooperative Oncology Group (ECOG) 0-1. • Adequate hematologic, coagulation, hepatic and renal function as defined per protocol. • Subjects must have histologically or cytological confirmed diagnosis of relapsed or refractory, advanced and/or metastatic NSCLC, EC, UC, TNBC, SCCHN, or cervical cancer who are not anymore candidates for or refuse standard therapy.
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E.4 | Principal exclusion criteria |
•Subject has uncontrolled intercurrent illness, including but not limited to: • Ongoing or active infection requiring intravenous treatment with anti-infective therapy that has been administered less than 2 weeks prior to first dose • Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia. • Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg, despite optimal medical management. • Ongoing or recent (within 1 year) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs). • Subjects with a history of grade 3 or higher irAEs that led to treatment discontinuation of a prior immunotherapy treatment should be excluded. Subjects with irAEs below grade 3 that led to discontinuation should be discussed with the sponsor. • Subjects with a prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade are excluded. • History of chronic liver disease or evidence of hepatic cirrhosis. • History of non-infectious pneumonitis that has required steroids or currently has pneumonitis. • History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of GEN1046. • Serious, non-healing wound, skin ulcer (of any grade), or bone fracture. • Any history of intracerebral arteriovenous malformation, cerebral aneurysm or progressive brain metastases or stroke. • Prior therapy: • Radiotherapy: Radiotherapy within 14 days prior to first GEN1046 administration. Palliative radiotherapy will be allowed. • Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1046 administration. Accepted exceptions are bisphosphonates (e.g., pamidronate, zoledronic acid, etc.) and denosumab. • Subjects who discontinued treatment due to disease progression within the first 6 weeks of a CPI containing treatment. • Prior treatment with a 4-1BB (CD137) targeted agent. • Prior treatment with a T-cell agonist or anti-CTLA-4 targeted agent within 12 weeks prior to the initiation of treatment. • Toxicities from previous anti-cancer therapies that have not resolved to baseline levels or to grade 1 or less with the exception of alopecia, anorexia, vitiligo, fatigue, hyperthyroidism, hypothyroidism, and peripheral neuropathy. Anorexia, hyperthyroidism, hypothyroidism, and peripheral neuropathy must have recovered to ≤ grade 2.
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E.5 End points |
E.5.1 | Primary end point(s) |
Dose Escalation: - Dose limiting Toxicities (DLTs) - Adverse events (AEs) and safety laboratory parameters
Dose Expansion: - Adverse events (AEs) and safety laboratory parameters
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Dose Escalation: - DLTs: dose limiting toxicities will be collected for the first two cycles i.e. DLT period of 42 days. - AEs: screening; Day 1, 2, 3, 8, 15 during Cycles 1-2; Days 1, 8, 15 during Cycle 3-4, Day 1 subsequent Cycles (5-PD); EoT; 4, 8, 12, subsequent every 12 (survival follow-up) Weeks after last dosing.
Dose Expansion: - AEs: screening; Day 1, 2, 3, 8, 15 during Cycles 1-2; Days 1, 8, 15 during Cycle 3-4, Day 1 subsequent Cycles (5-PD); EoT; 4, 8, 12, subsequent every 12 (survival follow-up) Weeks after last dosing.
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E.5.2 | Secondary end point(s) |
Dose Escalation: - PK parameters - Anti-Drug Antibody (ADA) response - Anti-tumor activity, i.e., reduction in tumor size according to RECIST 1.1: - Objective Response Rate (ORR) - Disease Control Rate (DCR) - Duration of Response (DoR)
Dose Expansion: - PK parameters - Anti-Drug Antibody (ADA) response - Anti-tumor activity, i.e., reduction in tumor size according to RECIST 1.1: - Objective Response Rate (ORR) - Disease Control Rate (DCR) - Duration of Response (DoR)
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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 | Yes |
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 | 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.8.3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 |
Czech Republic |
Hungary |
Israel |
Italy |
Poland |
Spain |
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 when the last subject dies or withdraws from the trial. However, maximal trial duration is 3 years after the last subject’s first treatment. |
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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 | 2 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |