GEN1046 Safety Trial in Patients With Malignant Solid Tumors

• ClinicalTrials.gov Identifier: NCT03917381
• Recruitment Status: Recruiting
• First Posted: April 17, 2019
• Last Update Posted: January 26, 2022
• 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: January 26, 2022
• Actual Study Start Date: May 14, 2019
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2022)

• 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: 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: throughout the study and up to 2 months after last subject last treatment ]
  Laboratory parameters graded by CTCAE v5.0
• For expansion cohort 1 only: Objective Response Rate (ORR) [ Time Frame: throughout the study and up to 2 months after last subject last treatment ]
  Objective Response Rate (ORR) per RECIST 1.1 assessed by Independent Review Committee (IRC)

Original 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

Current Secondary Outcome Measures (submitted: January 14, 2022)

• Objective Response Rate (ORR) [ Time Frame: throughout the study and up to 2 months after last subject last treatment ]
  Objective Response Rate (ORR) per RECIST 1.1 assessed by Independent Review Committee (IRC)
• PK parameters [ Time Frame: throughout the study and up to 2 months after last subject last treatment ]
  PK parameters
• Anti-Drug Antibody (ADA) response [ Time Frame: throughout the study and up to 2 months after last subject last treatment ]
  Anti-Drug Antibody (ADA) response
• Anti-tumor activity, ie, reduction in tumor size according to RECIST 1.1 [ Time Frame: throughout the study and up to 2 months after last subject last treatment ]
  • Objective Response Rate (ORR)
  • Disease Control Rate (DCR)
  • Duration of Response (DoR)
• For expansion cohort 1 only: Adverse events (AEs) [ Time Frame: throughout the study and up to 2 months after last subject last treatment ]
  Adverse events (AEs)
• For expansion cohort 1 only: Laboratory parameters [ Time Frame: throughout the study and up to 2 months after last subject last treatment ]
  Laboratory parameters graded by CTCAE v5.0
• For expansion cohort 1 only: Duration of response (DoR) [ Time Frame: throughout the study and up to 2 months after last subject last treatment ]
  Duration of response (DoR), PFS per RECIST 1.1 assessed by IRC
• For expansion cohort 1 only: ORR, DoR, PFS per RECIST 1.1 assessed by investigator [ Time Frame: throughout the study and up to 2 months after last subject last treatment ]
  ORR, DoR, PFS per RECIST 1.1 assessed by investigator
• For expansion cohort 1 only: Overall survival (OS) [ Time Frame: throughout the study and up to 2 months after last subject last treatment ]
  Overall survival (OS)

• 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 as monotherapy and in combination therapies 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 (in selected expansion cohorts GEN1046 will be administered intravenously once every 21 days for the first 2 cycles, and every 42 days in subsequent cycles)
• Biological: GEN1046 in combination with docetaxel (in a single expansion cohort)
  GEN1046 and docetaxel will be administered intravenously once every 21 days.
• Biological: GEN1046 in combination with pembrolizumab (in a separate expansion cohort)
  GEN1046 and pembrolizumab will be administered intravenously once every 21 days or every 42 days, respectively

Study Arms

Experimental: Arm

GEN1046 Open label, single arm trial where GEN1046 will be administered as monotherapy (or in combination with docetaxel or pembrolizumab in separate expansion cohorts)

Interventions:

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

• Publications *: Muik A, Garralda E, Altintas I, Gieseke F, Geva R, Ben-Ami E, Maurice-Dror C, Calvo E, LoRusso PM, Alonso G, Rodriguez-Ruiz ME, Schoedel KB, Blum JM, Sänger B, Salcedo TW, Burm SM, Stanganello E, Verzijl D, Vascotto F, Sette A, Quinkhardt J, Plantinga TS, Toker A, van den Brink EN, Fereshteh M, Diken M, Satijn D, Kreiter S, Breij ECW, Bajaj G, Lagkadinou E, Sasser K, Türeci Ö, Forssmann U, Ahmadi T, Şahin U, Jure-Kunkel M, Melero I. Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 and 4-1BB (GEN1046) in Patients with Advanced Refractory Solid Tumors. Cancer Discov. 2022 May 2;12(5):1248-1265. doi: 10.1158/2159-8290.CD-21-1345.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 14, 2022): 572
• Original Estimated Enrollment (submitted: April 12, 2019): 192
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key 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 two separate expansion cohorts: metastatic NSCLC without prior systemic treatment regimens for metastatic disease.

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

Key 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

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

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; 2018-003402-63 ( EudraCT Number )
• 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
• Current Responsible Party: Genmab
• Original Responsible Party: Same as current
• Current Study Sponsor: Genmab
• Original Study Sponsor: Same as current
• Collaborators: BioNTech SE
• Investigators: Not Provided
• PRS Account: Genmab
• Verification Date: January 2022