E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Malignant Solid Tumors, per protocol GCT1047-01 |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 10065147 |
E.1.2 | Term | Malignant solid tumor |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 maximum tolerated dose (MTD) and/or maximum administered dose (MAD) and recommended phase 2 dose (RP2D), or dose(s) to be studied in the Expansion part • Characterize the safety profile of GEN1047
Dose Expansion Part: • Evaluate antitumor activity based on response assessment criteria (RECIST v1.1) • Determine RP2D (unless determined in the Escalation part) |
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E.2.2 | Secondary objectives of the trial |
Dose Escalation Part: • Characterize pharmacokinetic (PK) profile • Evaluate immunogenicity of GEN1047 • Evaluate preliminary antitumor activity
Dose Expansion Part: • Evaluate antitumor activity based on response assessment criteria (RECIST v1.1) • Evaluate efficacy • Further describe the safety profile of GEN1047 • Further characterize PK profile • Further evaluate immunogenicity of GEN1047 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Criteria Escalation Part • Subject must have histologically or cytologically confirmed solid tumor(s) in any of the following selected indications for which there is no further available standard therapy likely to confer clinical benefit (or subject is not a candidate or has previously refused such earlier available therapy), and for whom, in the opinion of the investigator, experimental therapy with GEN1047 may be beneficial (breast cancer, endometrial cancer, ovarian cancer, squamous non-small-cell lung cancer [NSCLC-SCC]). • Subjects with ovarian cancer must have documented progressive disease (PD) on or after last prior treatment and within 60 days of Screening. • Must be at least 18 years of age (or the legal age of consent in the jurisdiction in which the trial is taking place) on the day of signing informed consent. • Must have either recurrence after, or progression on or lack of response to available relevant standard of care (SoC) anticancer therapies; or are deemed intolerant to or ineligible for, standard curative therapy in the recurrent setting. • Must have at least 1 measurable lesion per RECIST v1.1. The measurable lesion(s) must be outside the field of radiation therapy (RT) if there was prior treatment with RT. • Must have an Eastern Cooperative Oncology Group performance status (ECOGPS) score of 0 to 1 at Screening and on C1D1 pretreatment. • Should provide a tumor tissue sample during the Screening period and prior to C1D1. • Provide all tumor-assessing pre-trial CT scans since failure of last prior therapy.
Criteria Expansion Part • Subjects must have documented PD according to RECIST v1.1 on or after last prior treatment with latest scan performed a maximum of 28 days prior to the first dose. • Subject must have advanced (unresectable) or metastatic, histologically confirmed diagnosis (breast cancer, endometrial cancer, ovarian cancer, squamous non-small cell lung cancer [NSCLC-SCC]). • Must be a female and at least 18 years of age (or the legal age of consent in the jurisdiction in which the trial is taking place) at the time of consent. • Must have at least 1 measurable lesion per RECIST v1.1 as assessed by local investigator. • Must have an ECOG- PS score of 0 to 1 at Screening and on Cycle 1 Day 1 (C1D1) pretreatment. • Should provide a tumor tissue sample during the Screening period and prior to C1D1. • Provide all tumor-assessing pre-trial CT scans since failure of last prior therapy.
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E.4 | Principal exclusion criteria |
• Significant cardiovascular impairment within 6 months of the first dose of trial drug. • Subject with new or progressive brain metastases or spinal cord compression. • Subject has a history of bowel obstruction related to underlying disease. • Subject has been exposed to any prior therapy with a compound targeting CD3 and/or B7H4 or cell based therapies. • Current pneumonitis (any grade) including any radiological change of ongoing pneumonitis at baseline or history of non-infectious drug-, immune-, or radiation-related pneumonitis that required steroid. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Dose Escalation Part: • Dose-liming toxicities (DLTs) • Adverse events (AEs) and safety laboratory parameters
Dose Expansion Part: • Objective response rate (ORR) based on RECIST v1.1 as assessed by the independent review committee (IRC) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessments will be performed at regular intervals during the trial. Please see protocol for detailed schedule of events for Dose Escalation and Dose Expansion Parts. Safety follow-up visits will be conducted 30 days (+14 days; Dose Escalation and Expansion parts) and 60 days (+14 days; Expansion part only) after the subject receives the last dose of GEN1047. Thereafter, survival status will be assessed by contacting subjects every 3 months (±7 days), beginning from the day of the last dose of GEN1047 and continuing until the subject dies, withdraws consent for survival status follow up, or the trial ends. |
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E.5.2 | Secondary end point(s) |
Dose Escalation Part: • PK parameters (clearance; volume of distribution; AUClast; AUCinf; Cmax; Tmax; Ctrough; and t1/2) • Anti-drug antibody (ADA) incidence • Antitumor activity based on Response Evaluation Criteria in Solid Turmors (RECIST v1.1) as assessed by the investigator: Objective response rate (ORR), Duration of response (DOR), Time to response (TTR), Disease control rate (DCR)
Dose Expansion Part: • Antitumor activity, based on RECIST v1.1 as assessed by the IRC: DOR, TTR, DCR • Progression-free survival (PFS) based on RECIST v1.1 as assessed by the IRC; Overall Survival (OS) • AEs and safety laboratory parameters • PK parameters (clearance; volume of distribution; AUClast; AUCinf; Cmax; Tmax; Ctrough; t1/2) • ADA response |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Assessments will be performed at regular intervals during the trial. Please see protocol for detailed schedule of events for Dose Escalation and Dose Expansion Parts. Safety follow-up visits will be conducted 30 days (+14 days; Dose Escalation and Expansion parts) and 60 days (+14 days; Expansion part only) after the subject receives the last dose of GEN1047. Thereafter, survival status will be assessed by contacting subjects every 3 months (±7 days), beginning from the day of the last dose of GEN1047 and continuing until the subject dies, withdraws consent for survival status follow up, or the trial ends. |
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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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
United Kingdom |
United States |
Belgium |
Denmark |
France |
Italy |
Netherlands |
Poland |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
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, the maximum trial duration is 5 years after the last subject's first treatment 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 | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 | 18 |