ACASUNLIMAB for Endometrial carcinoma | Urothelial carcinoma | Triple-negative breast cancer | Squamous cell carcinoma of the head and neck | Cervical cancer

Inclusion criteria

• {"criterion_text":"- For Dose Escalation: • Have a histologically or cytologically confirmed non-CNS solid tumor that is metastatic or unresectable and for whom there is no available standard therapy"}
• {"criterion_text":"- For Expansion: • 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 standard therapy For separate expansion cohorts: metastatic NSCLC without prior systemic treatment regimens for metastatic disease."}
• {"criterion_text":"- For Both Dose Escalation and Expansion • Have measurable disease according to RECIST 1.1 • Have Eastern Cooperative Oncology Group (ECOG) 0-1 • Have an acceptable hematological status • Have acceptable liver function • Have an acceptable coagulation status • Have acceptable renal function"}

Exclusion criteria

• {"criterion_text":"- • Have uncontrolled intercurrent illness, including but not limited to: • Ongoing or active infection requiring intravenous treatment with antiinfective therapy, or any ongoing systemic inflammatory condition requiring further diagnostic work-up or management during screening. • 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 evidence of autoimmune disease • History of irAEs that led to prior checkpoint treatment discontinuation • Prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade • 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 acasunlimab • Serious, non-healing wound, skin ulcer (of any grade), or bone fracture • Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new (younger than 6 months) or progressive brain metastases or stroke"}
• {"criterion_text":"- • Prior therapy: • Radiotherapy within 14 days prior to first dose of acasunlimab. Note: 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 acasunlimab administration. Accepted exceptions are bisphosphonates (e.g., pamidronate, zoledronic acid, etc.) and denosumab • Toxicities from previous anti-cancer therapies that have not adequately resolved NOTE: Other protocol defined Inclusion/Exclusion criteria may apply."}

Primary endpoints

• {"endpoint_text":"- 1. Dose Escalation: Number of Participants With Dose Limiting Toxicity (DLT) Toxicities will be graded for severity according to Common Terminology Criteria for Adverse Events (CTCAE) criteria version 5.0.","definition_or_measurement_approach":"Toxicities will be graded for severity according to Common Terminology Criteria for Adverse Events (CTCAE) criteria version 5.0."}
• {"endpoint_text":"- 2. Dose Escalation and Monotherapy Expansion Cohorts: Number of Participants With Adverse Events (AEs)","definition_or_measurement_approach":""}
• {"endpoint_text":"- 3. Dose Escalation and Monotherapy Expansion Cohorts: Number of Participants With Shifts From Baseline in Safety Laboratory Parameters","definition_or_measurement_approach":""}
• {"endpoint_text":"- 4. Expansion Cohort 1: Objective Response Rate (ORR) ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on response evaluation criteria in solid tumours (RECIST).","definition_or_measurement_approach":"ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on RECIST v1.1."}

Secondary endpoints

• {"endpoint_text":"- 5. Expansion Cohort 1: Number of Participants With AEs","definition_or_measurement_approach":""}
• {"endpoint_text":"- 6. Expansion Cohort 1: Number of Participants With Shifts From Baseline in Safety Laboratory Parameters","definition_or_measurement_approach":""}
• {"endpoint_text":"- 7. Combination Therapy Expansion Cohorts: Number of Participants With AEs","definition_or_measurement_approach":""}
• {"endpoint_text":"- 8. Combination Therapy Expansion Cohorts: Number of Participants With Shifts From Baseline in Safety Laboratory Parameters","definition_or_measurement_approach":""}
• {"endpoint_text":"- 9. All Parts: Total Body Clearance (CL) of GEN1046","definition_or_measurement_approach":""}
• {"endpoint_text":"- 10. All Parts: Volume of Distribution (Vd) of GEN1046","definition_or_measurement_approach":""}
• {"endpoint_text":"- 11. All Parts: Area Under the Concentration-Time Curve from Time Zero to Day 21 (AUC21days) of GEN1046","definition_or_measurement_approach":""}
• {"endpoint_text":"- 12. All Parts: Area Under the Concentration-Time Curve from Time Zero to Infinity (AUCinf) of GEN1046","definition_or_measurement_approach":""}
• {"endpoint_text":"- 13. All Parts: Area Under the Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUClast) of GEN1046","definition_or_measurement_approach":""}
• {"endpoint_text":"- 14. All Parts: Maximum Observed Plasma Concentration (Cmax) of GEN1046","definition_or_measurement_approach":""}
• {"endpoint_text":"- 15. All Parts: Time to Reach Cmax (Tmax) of GEN1046","definition_or_measurement_approach":""}
• {"endpoint_text":"- 16. All Parts: Elimination Half-life (t½) of GEN1046","definition_or_measurement_approach":""}
• {"endpoint_text":"- 17. All Parts: Number of Participants with Anti-drug Antibodies (ADAs) Venous blood samples will be collected for measurement of serum concentrations of ADAs.","definition_or_measurement_approach":"Venous blood samples will be collected for measurement of serum concentrations of ADAs."}
• {"endpoint_text":"- 18. Dose Escalation and Expansion Cohorts 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13: ORR ORR is defined as the percentage of participants with BOR of CR or PR based on RECIST v1.1.","definition_or_measurement_approach":"ORR is defined as the percentage of participants with BOR of CR or PR based on RECIST v1.1."}
• {"endpoint_text":"- 19. Dose Escalation and Expansion Cohorts 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13: Disease Control Rate (DCR) The DCR is defined as the percentage of participants with confirmed BOR of CR, PR, or Stable Disease (SD) according to RECIST v1.1.","definition_or_measurement_approach":"DCR is defined as the percentage of participants with confirmed BOR of CR, PR, or Stable Disease (SD) according to RECIST v1.1."}
• {"endpoint_text":"- 20. All Parts: Duration of Response (DoR) DOR is defined as the time from first documentation of response (CR or PR) to the date of the first documented progression or death whichever occurs earlier based on RECIST v1.1.","definition_or_measurement_approach":"DOR is defined as the time from first documentation of response (CR or PR) to the date of the first documented progression or death whichever occurs earlier based on RECIST v1.1."}
• {"endpoint_text":"- 21. Expansion Cohort 1: Progression Free Survival (PFS) PFS is defined as the number of days from Day 1 in Cycle 1 to the first documented progression or death due to any cause, whichever occurs first based on RECIST version 1.1.","definition_or_measurement_approach":"PFS is defined as the number of days from Day 1 in Cycle 1 to the first documented progression or death due to any cause, whichever occurs first based on RECIST v1.1."}
• {"endpoint_text":"- 22. Expansion Cohort 1: Overall survival (OS) OS is defined as the number of days from Day 1 in Cycle 1 to death due to any cause.","definition_or_measurement_approach":"OS is defined as the number of days from Day 1 in Cycle 1 to death due to any cause."}

Hungary

Latest Decision Or Authorization Date

03-10-2025

Number Of Sites

1

Number Of Participants

2

Italy

Latest Decision Or Authorization Date

30-09-2025

Number Of Sites

4

Number Of Participants

13

Poland

Latest Decision Or Authorization Date

06-10-2025

Number Of Sites

4

Number Of Participants

29

Spain

Latest Decision Or Authorization Date

16-01-2026

Number Of Sites

10

Number Of Participants

251

Primary sponsor

Full Name

Genmab A/S

Organisation Type

Pharmaceutical company

Country Of Registered Address

Denmark

Contract research organisations

Name

Syneos Health Netherlands B.V.

Responsibilities

codes: 1,10,11,12,2,5,6,7

Name

Fortrea Development Limited

Responsibilities

SUSAR, Management of safety database and AE reporting

Name

Celerion Inc.

Responsibilities

PK/ADA testing

Third parties

• {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"Biomarker testing","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"Clinical chemistry, Clinical haematology, Serology/endocrinology, Immunophenotyping","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"Biomarker analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Fortrea Development Limited","duties_or_roles":"SUSAR, Management of safety database and AE reporting","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"Biomarker analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"Biomarker analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"roles/codes listed: 1,10,11,12,2,5,6,7","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Celerion Inc.","duties_or_roles":"PK/ADA testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG analysis/ review Medical image analysis/ review - X-ray, MRI, ultrasound, etc.","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Tempus Labs Inc.","duties_or_roles":"Biomarkers testing","organisation_type":"Non-Pharmaceutical company"}