GEN1046 in Combination With Anticancer Agents for the Treatment of Advanced Endometrial Cancer

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

26 Feb 2024 → 22 Apr 2024

Decision date (initial)

2023-07-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Genmab A/S

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Safety, Pharmacodynamic, Pharmacokinetic

Evaluate the antitumor activity of GEN1046 in combination with anticancer therapy in subjects with advanced endometrial cancer

Secondary objectives 3

1. Evaluate time to onset and durability of the antitumor response and the clinical benefit of GEN1046 in combination with pembrolizumab in subjects with advanced endometrial cancer
2. Further evaluate antitumor activity of GEN1046 in combination with pembrolizumab in subjects with advanced endometrial cancer
3. Assess safety and tolerability of GEN1046 in combination with pembrolizumab in subjects with advanced endometrial cancer

Conditions and MedDRA coding

Advanced Endometrial Cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Have a histologically confirmed diagnosis of advanced (unresectable, recurrent, and/or metastatic) endometrial carcinoma that is incurable and for which prior standard first-line treatment has failed.
2. Prior to C1D1, documentation of tumor dMMR/MSI-H status must be available based on previously performed mismatch repair (MMR)/microsatellite instability (MSI) testing results using immunohistochemistry (IHC), polymerase chain reaction (PCR), or next-generation sequencing (NGS) performed with a Food and Drug Administration (FDA)-approved/Conformitè Europëenne (CE)-marked test.
3. Must have progressed on or after at least 1 (but no more than 2) prior line(s) of a systemic chemotherapy regimen for unresectable and/or metastatic endometrial cancer of which at least 1 regimen of platinum-based treatment unless subject is ineligible for or intolerant to platinum.
4. Cohort A only: Must be treatment naive for CPIs including PD-1 or PD-L1 inhibitors and other immune CPIs (eg, anticytotoxic T-lymphocyte-associated protein 4 [CTLA-4], anti-lymphocyte-activation gene 3 [LAG3], anti-T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains [TIGIT]).
5. Cohort B only: Must have received and progressed on or after prior treatment with a PD-1/PD-L1 inhibitor alone or in combination. Moreover, the subject must fulfill the following:Duration of CPI containing treatment and best overall response (BOR) is known, and subject has received a minimum of 2 cycles of CPI.

Exclusion criteria 5

1. Has carcinosarcoma, malignant mixed Műllerian tumor, endometrial leiomyosarcoma, or endometrial stromal sarcomas.
2. Has been exposed to any of the following prior therapies/treatments within the specified timeframes: • Any prior treatment with any type of antitumor vaccine or autologous cell immunotherapy. • Radiotherapy within 14 days before the planned first dose of trial treatment with exception of palliative radiotherapy to bone lesions, which is allowed if completed 7 days prior to trial treatment start. Participants must have recovered from all radiation-related toxicities and/or complications prior to enrollment and must have tapered corticosteroid treatment to ≤10 mg/day at the time of first dose. • Treatment with an anticancer agent, including investigational vaccines within 28 days before or 5 times t1/2, whichever is shorter, prior to the planned first dose of trial treatment or is currently enrolled in an interventional trial. Note: Subjects who are in the follow-up phase of an interventional trial may participate if the subject has not received the investigational agent within 28 days of the first dose of trial treatment. • Prior treatment with live, attenuated vaccines within 30 days prior to initiation of trial treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Experimental and/or nonauthorized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations are not allowed. • Received granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) support within 4 weeks before the planned first dose of trial treatment.
3. Current pneumonitis (any grade) including any radiological change of ongoing pneumonitis at baseline or history of noninfectious drug-, immune-, or radiation-related pneumonitis that has required steroids.
4. Cohort A only: Prior exposure to immune CPIs (eg, anti-PD-1/anti-PD-L1, anti-CTLA-4, anti-LAG3, anti-TIGIT) or agents directed at costimulatory T-cell receptors (eg, 4-1BB, OX40)
5. Cohort B only: • Known history of Grade 3 or higher irAEs that led to treatment discontinuation of a prior immunotherapy treatment • Exposure to any of the following prior therapies/treatments within the specified timeframes: • Prior exposure to immune CPIs other than anti-PD-1/anti-PD-L1 (eg, anti-CTLA-4, anti-LAG3, anti-TIGIT) or agents directed at costimulatory T-cell receptors (eg, 4-1BB, OX40) • PD-1/PD-L1 antibody within 28 days before the planned first dose of trial treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 as assessed by the investigator

Secondary endpoints 2

1. Per RECIST 1.1 as assessed by the investigator: • Duration of response (DOR) • Time to response (TTR) • Disease control rate (DCR)
2. • Incidence and severity of adverse events (AEs) • Incidence and severity of laboratory abnormalities

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genmab A/S

Sponsor organisation

Genmab A/S

Address

Kalvebod Brygge 43

City

Copenhagen V

Postcode

1560

Country

Denmark

Scientific contact point

Organisation

Genmab A/S

Contact name

Genmab Trial Information

Public contact point

Organisation

Genmab A/S

Contact name

Genmab Trial Information

Third parties 12

Locations

5 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

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

Application history

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