GEN1047 for Solid Tumors - First in Human (FIH) Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genmab A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Dec 2021 → 26 Mar 2026

Decision date (initial)

2024-05-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Genmab A/S

External identifiers

EU CT number

2024-510722-10-00

EudraCT number

2021-001790-23

ClinicalTrials.gov

NCT05180474

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenomic, Dose response, Safety, Pharmacodynamic, Pharmacokinetic

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)

Secondary objectives 8

1. Dose Escalation Part: Characterize pharmacokinetic (PK) profile
2. Dose Escalation Part: Evaluate immunogenicity of GEN1047
3. Dose Escalation Part: Evaluate preliminary antitumor activity
4. Dose Expansion Part: Evaluate antitumor activity based on response assessment criteria (RECIST v1.1)
5. Dose Expansion Part: Evaluate efficacy
6. Dose Expansion Part: Further describe the safety profile of GEN1047
7. Dose Expansion Part: Further characterize PK profile
8. Dose Expansion Part: Further evaluate immunogenicity of GEN1047

Conditions and MedDRA coding

Malignant Solid Tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 21

1. Dose 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]).
2. Dose Expansion part – Stage 1: Subject must have advanced (unresectable) or metastatic, histologically confirmed diagnosis (breast cancer, endometrial cancer, ovarian cancer, squamous non-small cell lung cancer [NSCLC-SCC]).
3. Dose Expansion part – Stage 1: 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.
4. Dose Expansion part – Stage 1: Must have at least 1 measurable lesion per RECIST v1.1 as assessed by local investigator.
5. Dose Expansion part – Stage 1: Must have an ECOG- PS score of 0 to 1 at Screening and on Cycle 1 Day 1 (C1D1) pretreatment.
6. Dose Expansion part – Stage 1: Must provide a tumor tissue sample during the Screening period and prior to C1D1.
7. Dose Expansion part – Stage 1: Provide all tumor-assessing pre-trial CT scans since failure of last prior therapy.
8. Dose Escalation part: Subjects with ovarian cancer must have documented progressive disease (PD) on or after last prior treatment and within 60 days of Screening.
9. Dose Escalation part: 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.
10. Dose Escalation part: 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.
11. Dose Escalation part: 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.
12. Dose Escalation part: Must have an Eastern Cooperative Oncology Group performance status (ECOGPS) score of 0 to 1 at Screening and on C1D1 pretreatment.
13. Dose Escalation part: Should provide a tumor tissue sample during the Screening period and prior to C1D1.
14. Dose Escalation part: Provide all tumor-assessing pre-trial CT scans since failure of last prior therapy.
15. Dose Expansion part – Stage 1: 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.
16. Dose Expansion part – Stage 1b and 2: Subject must have advanced (unresectable) or metastatic, histologically confirmed diagnosis of breast cancer
17. Dose Expansion part – Stage 1b and 2: 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.
18. Dose Expansion part – Stage 1b and 2: 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.
19. Dose Expansion part – Stage 1b and 2: Must have at least 1 measurable lesion per RECIST v1.1 as assessed by the local investigator.
20. Dose Expansion part – Stage 1b and 2: Must have an ECOG-PS score of 0 to 1 at Screening and on C1D1 pretreatment.
21. Dose Expansion part – Stage 1b and 2: Must provide a tumor tissue sample during the Screening period and prior to C1D1.

Exclusion criteria 5

1. Significant cardiovascular impairment within 6 months of the first dose of trial drug
2. Subject with new or progressive brain metastases or spinal cord compression.
3. Subject has a history of bowel obstruction related to underlying disease (for Expansion Part Stage 1).
4. Subject has been exposed to any prior therapy with a compound targeting CD3 and/or B7H4 or cell based therapies.
5. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Dose Escalation Part: Dose-liming toxicities (DLTs)
2. Dose Escalation Part: Adverse events (AEs) and safety laboratory parameters
3. Dose Expansion Part: Objective response rate (ORR) based on RECIST v1.1 as assessed by the investigator

Secondary endpoints 8

1. Dose Escalation Part: PK parameters (clearance; volume of distribution; AUClast; AUCinf; Cmax; Tmax; Ctrough; and t1/2)
2. Dose Escalation Part: Anti-drug antibody (ADA) incidence
3. Dose Escalation Part: 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)
4. Dose Expansion Part: Antitumor activity, based on RECIST v1.1 as assessed by the investigator: DOR, TTR, DCR
5. Dose Expansion Part: Progression-free survival (PFS) based on RECIST v1.1 as assessed by the investigator; Overall Survival (OS)
6. Dose Expansion Part: AEs and safety laboratory parameters
7. Dose Expansion Part: PK parameters (clearance; volume of distribution; AUClast; AUCinf; Cmax; Tmax; Ctrough; t1/2)
8. Dose Expansion Part: ADA response

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genmab A/S

Sponsor organisation

Genmab A/S

Address

Carl Jacobsens Vej 30

City

Valby

Postcode

2500

Country

Denmark

Scientific contact point

Organisation

Genmab A/S

Contact name

Clinical Trial Information

Public contact point

Organisation

Genmab A/S

Contact name

Clinical Trial Information

Third parties 13

Locations

7 EU/EEA countries · 31 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 46 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications