A first-in-human trial of safety and efficacy of GEN1078 in participants with solid tumors.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genmab A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Jan 2025 → 11 Jun 2025

Decision date (initial)

2024-12-20

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: Others, Pharmacokinetic, Dose response, Safety, Therapy, Efficacy, Pharmacodynamic

Dose Escalation
- Determine maximum tolerated dose (MTD; if reached) or MAD and expansion doses of GEN1078
- Evaluate the safety and tolerability of GEN1078

Dose Expansion
- Assess anti-tumor activity of GEN1078
- If applicable: Determine recommended phase 2 dose (RP2D)

Secondary objectives 6

1. Dose Escalation: Establish PK profile after single and multiple doses of GEN1078
2. Dose Escalation: Evaluate immunogenicity
3. Dose Escalation: Assess the preliminary anti-tumor activity of GEN1078
4. Dose Expansion: Further assess the anti-tumor activity of GEN1078
5. Dose Expansion: Characterize PK and immunogenicity of GEN1078
6. Dose Expansion: Evaluate safety of GEN1078

Conditions and MedDRA coding

Malignant solid tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Must have at least 1 measurable lesion per RECIST v1.1 assessed by the investigator
2. Must have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 to 1.
3. Dose Escalation Only. Participant must have histologically or cytologically confirmed solid tumor(s) for which there is no further available standard therapy likely to confer clinical benefit (or participant is not a candidate or has previously refused such earlier available therapy), and for whom, in the opinion of the investigator, experimental therapy with GEN1078 may be beneficial
4. Dose Escalation Only. Must have either recurrence after, or progression on available relevant standard of care (SoC) anticancer therapies; or are deemed intolerant to or ineligible for, standard curative therapy in the recurrent setting
5. Expansion Only. Participant must have advanced (unresectable) or metastatic, histologically confirmed diagnosis of selected solid cancers.

Exclusion criteria 3

1. Has significant cardiovascular impairment within 6 months prior to the first dose of trial drug, including presence of unstable angina, myocardial infarction, congestive heart failure (New York Heart Association [NYHA] class III and IV), or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy.
2. Known unstable central nervous system (CNS) metastases or any active or history of carcinomatous meningitis.
3. Subject has been exposed to any prior therapies within the specified timeframes: - Prior therapy with a compound targeting the same targets as GEN1078 or any cell-based therapies. - Radiotherapy within 14 days prior to C1D1. Palliative radiotherapy of bone metastases up to 7 days prior to C1D1 will be allowed. - Treatment with any investigational or non-investigational anticancer agent (including investigational vaccines) or used an invasive investigational medical device within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the first dose of GEN1078. - Chemotherapy within 2 weeks prior to the first dose of GEN1078. - Prophylaxis with live, attenuated vaccines within 28 days prior to first dose of GEN1078; or prophylaxis with the first and/or subsequent injection(s) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid vaccine within 14 days prior to first dose of GEN1078. - Chronic systemic immunosuppressive treatment, including corticosteroids, ie, prednisone >10 milligrams (mg) daily (or equivalent) or a cumulative dose >140 mg prednisone within 14 days (or equivalent) before the first dose of GEN1078. Replacement therapy (eg, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted. - Has received granulocyte colony-stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor support within 2 weeks prior to the first dose GEN1078 or being chronically transfusion dependent. - Has received other T-cell activating surface marker. Note: Prior treatment with anti-T-cell Ig and ITIM domain (aTIGIT), anti-programmed cell death protein 1 (aPD1), anti-programmed death-ligand 1 (aPDL1), anti-lymphocyte activation gene 3 protein (aLAG3), anti-cytotoxic T-lymphocyte-associated protein 4 (aCTLA-4) is allowed. - The initiation of growth factors and bisphosphonates is not allowed during the first 4 weeks of GEN1078 administration, unless agreed upon by the investigator and sponsor medical monitor. However, the use of receptor activator of nuclear factor kappa-Β ligand (RANK-L) inhibitors and bisphosphonates (if on stable dose for at least 4 weeks) is permitted while participating in this trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Dose Escalation: Number of Participants with Dose-limiting Toxicities (DLTs)
2. Dose Escalation: Number of Participants with Adverse Events (AEs)
3. Dose Expansion: Confirmed Objective Response Rate (ORR).

Secondary endpoints 14

1. Dose-Escalation and Expansion: Clearance (CL) of GEN1078
2. Dose-Escalation and Expansion: Volume of Distribution (Vd) of GEN1078
3. Dose-Escalation and Expansion: Area Under the Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUC0-last) of GEN1078
4. Dose-Escalation and Expansion: Area Under the Concentration-Time Curve from Time Zero to Infinity (AUC0-∞) of GEN1078
5. Dose-Escalation and Expansion: Maximum Observed Plasma Concentration (Cmax) of GEN1078
6. Dose-Escalation and Expansion: Time to Reach Cmax (Tmax) for GEN1078
7. Dose-Escalation and Expansion: Predose Concentration for GEN1078
8. Dose-Escalation and Expansion: Terminal Half-life (t½) of GEN1078
9. Dose-Escalation and Expansion: Number of Participants with Anti-drug Antibodies (ADAs)
10. Dose Escalation: Confirmed ORR.
11. Dose-Escalation and Expansion: Duration of Response (DOR).
12. Dose-Escalation and Expansion: Disease Control Rate (DCR).
13. Dose-Escalation and Expansion: Time to Response (TTR).
14. Dose Expansion: Number of Participants with AEs

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 12

Locations

2 EU/EEA countries · 7 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 2 · 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 16 files

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

Application history

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