GEN1042 Safety Trial and Anti-tumor Activity in Subjects With Malignant Solid Tumors

• ClinicalTrials.gov Identifier: NCT04083599
• Recruitment Status: Recruiting
• First Posted: September 10, 2019
• Last Update Posted: May 7, 2024
• Sponsor: Genmab
• Collaborator: BioNTech SE
• Information provided by (Responsible Party): Genmab

Tracking Information

• First Submitted Date: September 6, 2019
• First Posted Date: September 10, 2019
• Last Update Posted Date: May 7, 2024
• Actual Study Start Date: September 17, 2019
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 24, 2022)

• Percentage of Subjects With Dose-Limiting Toxicities (DLT) [ Time Frame: First Cycle (21 days) ]
  Occurrence of Dose-Limiting Toxicities (DLT) assessed by the Investigator
• Objective Response Rate (ORR) [ Time Frame: From the start of the study treatment until disease progression/death/ lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first. (an expected average of 10 months) ]
  Defined as proportion of participants who have a confirmed partial or complete response (PR or CR). Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Original Primary Outcome Measures (submitted: September 6, 2019)

• Dose Limiting Toxicity (DLT) [ Time Frame: First Cycle (21 days) ]
  Determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D)
• Adverse Events (AEs) [ Time Frame: Throughout study until the end of the safety follow-up period (2 months after last dose)] ]
  Incidence of adverse events as assessed by CTCAE v5.0

Current Secondary Outcome Measures (submitted: December 24, 2022)

• Percentage of Subjects with Adverse Events and Serious Adverse Events [ Time Frame: Baseline up to 90 Days After the Last Dose, assessed up to 36 months after the last subject's first treatment in the trial. ]
  Incidence of Adverse Events and Serious Adverse Events as assessed by NCI CTCAE V5.0
• Duration of Object Response (DOR) [ Time Frame: From the start of the study treatment until disease progression/death/ lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first. (an expected average of 10 months) ]
  Defined as time from the first documentation of objective response (CR or PR) to the date of first PD or death.
• Disease Control Rate (DCR) [ Time Frame: From the start of the study treatment until disease progression/death/ lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first. (an expected average of 10 months) ]
  Determined by Investigator Using RECIST Version 1.1
• Progression-Free Survival (PFS) [ Time Frame: From the start of the study treatment until disease progression/death whichever occurs first. (an expected average of 10 months) ]
  Defined as the time from start of study treatment to first documented progression per RECIST Version 1.1 by investigator assessment or death due to any cause, whichever occurs first.
• Overall survival (OS) [ Time Frame: From the start of the study treatment until death due to any cause, assessed up to 36 months after the last subject's first treatment in the trial. ]
  Defined as the time from start of study treatment to date of death due to any cause.
• Dose Escalation: Maximum Concentration (Cmax) of GEN1042 [ Time Frame: Cycle (Cy) 1 Day (D) 1 before GEN1042 infusion (BI) and End of Infusion (EOI), Cy1 D2, 3, 8, 15, Cy2 BI, EOI on D1, D 2, 3, 8, 15, and then D1 of Cy 3, 5, 7, 11, 15 and every 4 cycles thereafter (up to end of treatment) (Cy =21 days) ]
  Pharmacokinetic (PK) parameters of GEN1042, and incidence of anti-drug antibodies Dose Escalation: Maximum Concentration (Cmax) of GEN1042
• Dose Escalation: Area Under the Concentration Time Curve (AUC) of GEN1042 [ Time Frame: Cycle (Cy) 1 Day (D) 1 before GEN1042 infusion (BI) and , End of GEN1042 Infusion (EOI), Cy1 D2, 3, 8, 15, Cy2 BI, EOI on D1, D 2, 3, 8, 15, and then D1 of Cy 3, 5, 7, 11, 15 and every 4 cycles thereafter (up to end of treatment) (Cy =21 days) ]
  Pharmacokinetic (PK) parameters of GEN1042, and incidence of anti-drug antibodies Dose Escalation: Area Under the Concentration Time Curve (AUC) of GEN1042
• Dose Escalation: Half-life (t1/2) of GEN1042 [ Time Frame: Cycle (Cy) 1 Day (D) 1 before GEN1042 infusion (BI) and End of Infusion (EOI), Cy1 D2, 3, 8, 15, Cy2 BI, EOI on D1, D 2, 3, 8, 15, and then D1 of Cy 3, 5, 7, 11, 15 and every 4 cycles thereafter (up to end of treatment) (Cy =21 days) ]
  Dose Escalation: Half-life (t1/2) of GEN1042
• Dose Expansion: Area Under the Concentration Time Curve (AUC) of GEN1042 [ Time Frame: Cy 1 BI, EOI on D1, D8, 15, Cy 2 BI, EOI on D1, D8, 15, and then D1 of Cy 3, 5, 7, 11, 15 and every 4 cycles thereafter (up to end of treatment) (Cy =21 days) ]
  Dose Expansion: Area Under the Concentration Time Curve (AUC) of GEN1042
• Dose Expansion: Maximum Concentration (Cmax) of GEN1042 [ Time Frame: Cy 1 BI, EOI on D1, D8, 15, Cy 2 BI, EOI on D1, D8, 15, and then D1 of Cy 3, 5, 7, 11, 15 and every 4 cycles thereafter (up to end of treatment) (Cy =21 days) ]
  Dose Expansion: Maximum Concentration (Cmax) of GEN1042
• Dose Escalation: Incidence of ADA response to GEN1042 [ Time Frame: BI on Cy 1, 2, 3, 5, 7, 11, 15 and every 4 cycles thereafter (up to end of treatment), safety follow-up visit (SFU) (30 and 90 days post final dose) (Cy =21 days) ]
  Dose Escalation: Incidence of ADA response to GEN1042responses to GEN1042
• Dose Expansion: Incidence of ADA response to GEN1042 [ Time Frame: BI on Cy 1, 2, 3, 5, 7, 11, 15 and every 4 cycles thereafter (up to end of treatment), SFU (30 and 90 days post final dose) (Cy =21 days) ]
  Dose Expansion: Incidence of ADA response to GEN1042

• 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: GEN1042 Safety Trial and Anti-tumor Activity in Subjects With Malignant Solid Tumors
• Official Title: A First-in-Human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety and Anti-tumor Activity of GEN1042 in Subjects With Malignant Solid Tumors
• Brief Summary: To evaluate the safety and anti-tumor activity of GEN1042 in patients with metastatic or locally advanced solid tumors.
• Detailed Description: This is an open-label, multicenter phase 1/2 study designed to assess the safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of GEN1042 administered as a monotherapy or in combination in subjects with metastatic or locally advanced solid tumors.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Malignant Solid Tumor
• Non Small Cell Lung Cancer (NSCLC)
• Colorectal Cancer (CRC)
• Melanoma
• Head and Neck Squamous Cell Carcinoma (HNSCC)
• Pancreatic Ductal Adenocarcinoma (PDAC)

Intervention

• Biological: GEN1042
  Intravenous
• Drug: Pembrolizumab
  Intravenous
• Drug: Cisplatin
  Intravenous
• Drug: Carboplatin
  Intravenous
• Drug: 5-FU
  Intravenous
• Drug: Gemcitabine
  Intravenous
• Drug: Nab paclitaxel
  Intravenous
• Drug: Pemetrexed
  Intravenous
• Drug: Paclitaxel
  Intravenous

Study Arms

• Experimental: Monotherapy - Dose Escalation and Dose Expansion parts
  Escalating doses of GEN1042 monotherapy in subjects with non-central nervous system (CNS) solid malignant tumors followed by monotherapy expansion cohorts at selected dose(s) in subjects with relapsed or refractory, advanced and/or metastatic melanoma, or non-small-cell lung cancer (NSCLC), or colorectal cancer (CRC).
  Intervention: Biological: GEN1042
• Experimental: Combination Therapy - Dose Expansion Part
  GEN1042 safety and efficacy will be evaluated in combination with pembrolizumab with or without chemotherapy in treatment-naive subjects with advanced or metastatic melanoma, non-small-cell lung cancer [NSCLC], head and neck squamous cell carcinoma [HNSCC], and pancreatic cancer.
  Interventions:

  • Biological: GEN1042
  • Drug: Pembrolizumab
  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: 5-FU
  • Drug: Gemcitabine
  • Drug: Nab paclitaxel
  • Drug: Pemetrexed
  • Drug: Paclitaxel

• Publications *: Muik A, Adams 3rd HC, Gieseke F, Altintas I, Schoedel KB, Blum JM, Sanger B, Burm SM, Stanganello E, Verzijl D, Spires VM, Vascotto F, Toker A, Quinkhardt J, Fereshteh M, Diken M, Satijn DPE, Kreiter S, Ahmadi T, Breij ECW, Tureci O, Sasser K, Sahin U, Jure-Kunkel M. DuoBody-CD40x4-1BB induces dendritic-cell maturation and enhances T-cell activation through conditional CD40 and 4-1BB agonist activity. J Immunother Cancer. 2022 Jun;10(6):e004322. doi: 10.1136/jitc-2021-004322. Erratum In: J Immunother Cancer. 2022 Sep;10(9):

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 4, 2023): 1287
• Original Estimated Enrollment (submitted: September 6, 2019): 126
• Estimated Study Completion Date: October 2025
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

Monotherapy - Dose Escalation and Dose Expansion Parts

• Subjects with non-CNS solid tumors that is metastatic or unresectable and for whom there is no available standard therapy.
• Subjects with a confirmed diagnosis of relapsed or refractory, advanced and/or metastatic melanoma, NSCLC, or CRC and for whom there is no available standard therapy

Combination Therapy - Dose Expansion Part

• Subjects with unresectable Stage III or Stage IV melanoma with no prior systemic anticancer therapy for unresectable or metastatic disease. Primary ocular or mucosal melanoma is excluded.
• Subjects with Stage IV metastatic or recurrent NSCLC with no prior systemic anticancer therapy, no actionable mutation.
• Subjects with recurrent or metastatic HNSCC with no prior systemic therapy administered in the recurrent or metastatic setting.
• Subjects with confirmed metastatic PDAC with no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease.

General (all phases):

• Must be age ≥ 18 years of age on the day of signing informed consent, or the legal age of consent in the jurisdiction in which the trial is taking place.
• Measurable disease according to RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) 0-1
• Normal or adequate liver, renal, cardiac and bone marrow function

Key Exclusion Criteria:

Monotherapy - Dose Escalation and Dose Expansion Parts

• Treatment with an anti-cancer agent (within 21 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1042 administration
• Radiotherapy within 14 days prior to first GEN1042 administration
• Toxicities from previous anti-cancer therapies that have not resolved

Combination Therapy - Dose Expansion Part

• Has received prior systemic cytotoxic chemotherapy, biological therapy, OR major surgery within 3 weeks or at least 5 half-lives of the drug (whichever is shorter) of the first dose of trial treatment.
• Radiotherapy within 14 days of start of trial treatment or received lung radiation therapy of > 30 Gy within 6 months of the first dose of trial treatment.

General (all phases)

• Subject has an active, known, or suspected autoimmune disease.
• History of non-infectious pneumonitis that required steroids or currently has pneumonitis.
• History of ≥ grade 3 allergic reactions to monoclonal antibody (mAb) therapy
• Subject with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment.

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 A/S Trial Information; +4570202728; clinicaltrials@genmab.com

• Listed Location Countries: Denmark, France, Georgia, Germany, Israel, Italy, Korea, Republic of, Moldova, Republic of, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04083599
• Other Study ID Numbers: GCT1042-01; 2018-003716-47 ( EudraCT Number ); IRAS ID: 263292 ( Registry Identifier: UK Research Summaries Database ); MOH_2023-07-31_012855 ( Registry Identifier: Israel MyTrials ); 2023-508526-10-00 ( EU Trial (CTIS) 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

IPD Sharing Statement

• Plan to Share IPD: No

• 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: May 2024