GEN1046 Safety Trial in Patients With Malignant Solid Tumors

• ClinicalTrials.gov Identifier: NCT03917381
• Recruitment Status: Recruiting
• First Posted: April 17, 2019
• Last Update Posted: June 2, 2021
• Sponsor: Genmab
• Collaborator: BioNTech SE
• Information provided by (Responsible Party): Genmab

Tracking Information

• First Submitted Date: April 11, 2019
• First Posted Date: April 17, 2019
• Last Update Posted Date: June 2, 2021
• Actual Study Start Date: May 14, 2019
• Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 12, 2019)

• Dose limiting toxicity (DLT) [ Time Frame: DLTs are assessed during the first cycle (21 days) in each cohort] ]
  to determine maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)
• Adverse events [ Time Frame: AEs are collected throughout the study and up to 2 months after last subject last treatment ]
  Incidence of treatment-emergent adverse events as assessed by CTCAE v5.0
• Safety laboratory parameters (hematology, biochemistry, coagulation, endocrines) [ Time Frame: Safety laboratory data are collected throughout the study and up to 2 months after last subject last treatment ]
  Laboratory parameters graded by CTCAE v5.0

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: GEN1046 Safety Trial in Patients With Malignant Solid Tumors
• Official Title: First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1046 in Subjects With Malignant Solid Tumors
• Brief Summary: The purpose of the trial is to evaluate the safety of GEN1046 in patients with malignant solid tumors
• Detailed Description: The trial is an open-label, multi-center safety trial of GEN1046. The trial consists of two parts, a dose escalation part (phase 1, first-in-human (FIH) and an expansion part (phase 2a)). The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) has been determined.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:

The starting dose is administered as a flat dose. Dose escalation steps are based on safety data

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Solid Tumors
• Non-small Cell Lung Cancer
• Urothelial Carcinoma
• Endometrial Carcinoma
• Triple Negative Breast Cancer
• Squamous Cell Carcinoma of the Head and Neck
• Cervical Cancer

Intervention

• Biological: GEN1046
  GEN1046 will be administered intravenously once every 21 days.
• Biological: GEN1046 in combination with docetaxel (in a single expansion cohort)
  GEN1046 and docetaxel will be administered intravenously once every 21 days.

Study Arms

Experimental: Arm

GEN1046 Open label, single arm trial where GEN1046 will be administered (in one expansion cohort in combination with docetaxel)

Interventions:

• Biological: GEN1046
• Biological: GEN1046 in combination with docetaxel (in a single expansion cohort)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 30, 2021): 512
• Original Estimated Enrollment (submitted: April 12, 2019): 192
• Estimated Study Completion Date: December 2022
• Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

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

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 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:

• Have uncontrolled intercurrent illness, including but not limited to:

  • Ongoing or active infection requiring intravenous treatment with antiinfective therapy
  • 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 GEN1046
  • 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

• Prior therapy:

  • Radiotherapy: Radiotherapy within 14 days prior to first GEN1046 administration. 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 GEN1046 administration. Accepted exceptions are bisphosphonates (e.g., pamidronate, zoledronic acid, etc.) and denosumab
• Toxicities from previous anti-cancer therapies that have not adequately resolved

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Genmab Trial Information; +4570202728; clinicaltrials@genmab.com

• Listed Location Countries: Czechia, Hungary, Israel, Italy, Poland, Spain, United States

Administrative Information

• NCT Number: NCT03917381
• Other Study ID Numbers: GCT1046-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Genmab
• Study Sponsor: Genmab
• Collaborators: BioNTech SE
• Investigators: Not Provided
• PRS Account: Genmab
• Verification Date: June 2021