GEN1046 Safety Trial in Patients With Malignant 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

30 Apr 2019 → ongoing

Decision date (initial)

2024-07-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Genmab A/S

External identifiers

EU CT number

2023-509059-15-00

EudraCT number

2018-003402-63

ClinicalTrials.gov

NCT03917381

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

- Determine the MTD and/or the recommended Phase 2 dose (RP2D)
- Establish the safety profile of GEN1046
- Evaluate clinical efficacy

Secondary objectives 1

1. • Characterize PK profile of GEN1046; • Evaluate immunogenicity of GEN1046; • Evaluate anti-tumor activity; • Evaluate the safety profile of GEN1046 in combination with docetaxel; • Evaluate the safety profile of GEN1046 in combination with pembrolizumab; • Evaluate the safety profile of GEN1046 in combination with pembrolizumab and platinum-based chemotherapy doublets (pemetrexed + cisplatin OR carboplatin ; carboplatin + paclitaxel OR nab-paclitaxel; • Evaluate the safety profile of GEN1046;• Further evaluate clinical efficacy; • Characterize PK and immunogenicity of GEN1046

Conditions and MedDRA coding

Malignant solid tumors: endometrial carcinoma (EC), urothelial carcinoma (UC), triple-negative breast cancer (TNBC), squamous cell carcinoma of the head and neck (SCCHN), or cervical cancer.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 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
2. 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.
3. 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 2

1. • 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
2. • 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. 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.
2. 2. Dose Escalation and Monotherapy Expansion Cohorts: Number of Participants With Adverse Events (AEs)
3. 3. Dose Escalation and Monotherapy Expansion Cohorts: Number of Participants With Shifts From Baseline in Safety Laboratory Parameters
4. 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).

Secondary endpoints 18

1. 5. Expansion Cohort 1: Number of Participants With AEs
2. 6. Expansion Cohort 1: Number of Participants With Shifts From Baseline in Safety Laboratory Parameters
3. 7. Combination Therapy Expansion Cohorts: Number of Participants With AEs
4. 8. Combination Therapy Expansion Cohorts: Number of Participants With Shifts From Baseline in Safety Laboratory Parameters
5. 9. All Parts: Total Body Clearance (CL) of GEN1046
6. 10. All Parts: Volume of Distribution (Vd) of GEN1046
7. 11. All Parts: Area Under the Concentration-Time Curve from Time Zero to Day 21 (AUC21days) of GEN1046
8. 12. All Parts: Area Under the Concentration-Time Curve from Time Zero to Infinity (AUCinf) of GEN1046
9. 13. All Parts: Area Under the Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUClast) of GEN1046
10. 14. All Parts: Maximum Observed Plasma Concentration (Cmax) of GEN1046
11. 15. All Parts: Time to Reach Cmax (Tmax) of GEN1046
12. 16. All Parts: Elimination Half-life (t½) of GEN1046
13. 17. All Parts: Number of Participants with Anti-drug Antibodies (ADAs) Venous blood samples will be collected for measurement of serum concentrations of ADAs.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.

Investigational products

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

Test 8

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 10

Locations

4 EU/EEA countries · 19 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 64 files

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

Application history

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