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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04083599
Recruitment Status : Recruiting
First Posted : September 10, 2019
Last Update Posted : October 1, 2021
Sponsor:
Collaborator:
BioNTech SE
Information provided by (Responsible Party):
Genmab

Brief Summary:
To evaluate the safety and anti-tumor activity of GEN1042 in patients with metastatic or locally advanced solid tumors

Condition or disease Intervention/treatment Phase
Malignant Solid Tumor Non Small Cell Lung Cancer (NSCLC) Colorectal Cancer (CRC) Melanoma Head and Neck Squamous Cell Carcinoma (HNSCC) Pancreatic Ductal Adenocarcinoma (PDAC) Biological: GEN1042 Drug: Pembrolizumab Drug: Cisplatin Drug: Carboplatin Drug: 5-FU Drug: Gemcitabine Drug: Nab-Paclitaxel Phase 1 Phase 2

Detailed Description:

This is an open-label, multicenter phase 1/2 study designed to assess the safety, pharmacokinetics, pharmacodynamics and activity of GEN1042 administered as a monotherapy or in combination in subjects with metastatic or locally advanced solid tumors. The trial consists of 4 parts: a GEN1042 monotherapy dose escalation (phase 1a), a GEN1042 monotherapy expansion (phase 2a), a combination therapy safety run in (phase 1b), and a combination therapy expansion (phase 2b).

The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) has been determined.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 447 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 17, 2019
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GEN1042 monotherapy dose escalation (phase 1a)
• All NON-CNS solid tumors
Biological: GEN1042
GEN1042 administered intravenously every 21 days (1Q3W).

Experimental: GEN1042 monotherapy expansion (phase 2a)
  • NSCLC
  • Melanoma
  • CRC
Biological: GEN1042
GEN1042 administered intravenously every 21 days (1Q3W) as per the recommended Phase 2 dose (RP2D) from monotherapy dose escalation.

Experimental: Combination safety run-in (phase 1b) for NSCLC, HNSCC and Melanoma
  • 1L NSCLC
  • 1L HNSCC
  • 1L Melanoma
Biological: GEN1042
GEN1042 administered intravenously every 21 days (1Q3W).

Drug: Pembrolizumab
Pembrolizumab administered intravenously every 21 days (1Q3W).

Experimental: Combination safety run-in (phase 1b) for HNSCC
• 1L HNSCC
Biological: GEN1042
GEN1042 administered intravenously every 21 days (1Q3W).

Drug: Pembrolizumab
Pembrolizumab administered intravenously every 21 days (1Q3W).

Drug: Cisplatin
Cis-/carboplatin + 5FU administered intravenously in combination with GEN1042 + pembrolizumab 1Q3W for 6 cycles followed by GEN1042 +pembrolizumab 1Q3W.

Drug: Carboplatin
Cis-/carboplatin + 5FU administered intravenously in combination with GEN1042 + pembrolizumab 1Q3W for 6 cycles followed by GEN1042 +pembrolizumab 1Q3W.

Drug: 5-FU
Cis-/carboplatin + 5FU administered intravenously in combination with GEN1042 + pembrolizumab 1Q3W for 6 cycles followed by GEN1042 +pembrolizumab 1Q3W.

Experimental: Combination safety run-in (phase 1b) for PDAC
• 1L PDAC
Biological: GEN1042
GEN1042 administered intravenously every 21 days (1Q3W).

Drug: Pembrolizumab
Pembrolizumab administered intravenously every 21 days (1Q3W).

Drug: Gemcitabine
a: GEN1042 1Q3W+ gemcitabine + nab-paclitaxel 2Q3W for a total of 8 cycles; b: GEN1042 + pembrolizumab 1Q3W+ gemcitabine + nab-paclitaxel 2Q3W for 8 cycles followed by GEN1042 + pembrolizumab 1Q3W

Drug: Nab-Paclitaxel
a: GEN1042 1Q3W+ gemcitabine + nab-paclitaxel 2Q3W for a total of 8 cycles; b: GEN1042 + pembrolizumab 1Q3W+ gemcitabine + nab-paclitaxel 2Q3W for 8 cycles followed by GEN1042 + pembrolizumab 1Q3W

Experimental: Combination therapy expansion (phase 2b) for Melanoma
• 1L Melanoma
Biological: GEN1042
GEN1042 administered intravenously every 21 days (1Q3W).

Drug: Pembrolizumab
Pembrolizumab administered intravenously every 21 days (1Q3W).

Experimental: Combination therapy expansion (phase 2b) for NSCLC
• 1L NSCLC
Biological: GEN1042
GEN1042 administered intravenously every 21 days (1Q3W).

Drug: Pembrolizumab
Pembrolizumab administered intravenously every 21 days (1Q3W).

Experimental: Combination therapy expansion (phase 2b) for HNSCC with pembrolizumab
• 1L HNSCC
Biological: GEN1042
GEN1042 administered intravenously every 21 days (1Q3W).

Drug: Pembrolizumab
Pembrolizumab administered intravenously every 21 days (1Q3W).

Experimental: Combination therapy expansion (phase 2b) for HNSCC with pembrolizumab + chemotherapy
• 1L HNSCC
Biological: GEN1042
GEN1042 administered intravenously every 21 days (1Q3W).

Drug: Pembrolizumab
Pembrolizumab administered intravenously every 21 days (1Q3W).

Drug: Cisplatin
Cis-/carboplatin + 5FU administered intravenously in combination with GEN1042 + pembrolizumab 1Q3W for 6 cycles followed by GEN1042 +pembrolizumab 1Q3W.

Drug: Carboplatin
Cis-/carboplatin + 5FU administered intravenously in combination with GEN1042 + pembrolizumab 1Q3W for 6 cycles followed by GEN1042 +pembrolizumab 1Q3W.

Drug: 5-FU
Cis-/carboplatin + 5FU administered intravenously in combination with GEN1042 + pembrolizumab 1Q3W for 6 cycles followed by GEN1042 +pembrolizumab 1Q3W.

Experimental: Combination therapy expansion (phase 2b) for PDAC
• 1L PDAC
Biological: GEN1042
GEN1042 administered intravenously every 21 days (1Q3W).

Drug: Pembrolizumab
Pembrolizumab administered intravenously every 21 days (1Q3W).

Drug: Gemcitabine
a: GEN1042 1Q3W+ gemcitabine + nab-paclitaxel 2Q3W for a total of 8 cycles; b: GEN1042 + pembrolizumab 1Q3W+ gemcitabine + nab-paclitaxel 2Q3W for 8 cycles followed by GEN1042 + pembrolizumab 1Q3W

Drug: Nab-Paclitaxel
a: GEN1042 1Q3W+ gemcitabine + nab-paclitaxel 2Q3W for a total of 8 cycles; b: GEN1042 + pembrolizumab 1Q3W+ gemcitabine + nab-paclitaxel 2Q3W for 8 cycles followed by GEN1042 + pembrolizumab 1Q3W




Primary Outcome Measures :
  1. Occurrence of Dose-Limiting Toxicities (DLT) assessed by the Investigator to be possibly, probably or definitely related to GEN1042 (phase 1a) and GEN1042 combination regimen (phase 1b) [ Time Frame: First Cycle (21 days), assessed up to 36 months after the last subject's first treatment in the trial. ]
    Percentage of Subjects With Dose-Limiting Toxicities (DLT)

  2. Maximum Tolerated Dose (MTD) assessed as the highest dose of GEN1042 administered alone (phase 1a) or in combination regimen (phase 1b) [ Time Frame: First Cycle (21 days), assessed up to 36 months after the last subject's first treatment in the trial. ]
    Maximum Tolerated Dose (MTD) of GEN1042

  3. Recommended Phase 2 Dose (RP2D) based on available safety and dosing information of GEN1042 administered alone (phase 1a) and in combination regimen (phase 1b) [ Time Frame: First Cycle (21 days), assessed up to 36 months after the last subject's first treatment in the trial. ]
    Recommended Phase 2 Dose of GEN1042

  4. Best Overall Response Rate (ORR) assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for dose expansion as monotherapy (phase 2a) and in combination (phase 2b) [ Time Frame: Baseline up to PD or start of the next line of treatment or death due to any cause, whichever occurs first, assessed up to 36 months after the last subject's first treatment in the trial. ]
    Percentage of subjects with best Overall Response Rate (ORR), as determined by Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Dose Escalation: Percentage of Participants with Incidence of anti-drug antibody (ADAs) responses 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: Percentage of Participants with Incidence of anti-drug antibody (ADAs) responses to GEN1042

  7. Dose Expansion: Percentage of Participants with Incidence of ADA response to GEN104 [ 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: Percentage of Participants with Incidence of ADA response to GEN104

  8. Incidence of Adverse Events and Serious Adverse Events as assessed by NCI CTCAE V5.0 for GEN1042 administered alone (phase 1a) and in combination regimen (phase 1b) [ 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. ]
    Percentage of Subjects with Adverse Events and Serious Adverse Events

  9. Progression-Free Survival (PFS) determined by Investigator using RECIST 1.1 for dose expansion as monotherapy (phase 2a) and in combination (phase 2b) [ Time Frame: Baseline up to PD or start of the next line of treatment or death due to any cause, whichever occurs first, assessed up to 36 months after the last subject's first treatment in the trial. ]
    Progression-Free Survival (PFS), as Determined by Investigator Using RECIST Version 1.1

  10. Duration of Object Response (DOR) determined by Investigator per RECIST 1.1. for dose expansion as monotherapy (phase 2a) and in combination (phase 2b) [ Time Frame: Baseline up to PD or start of the next line of treatment or death due to any cause, whichever occurs first, assessed up to 36 months after the last subject's first treatment in the trial. ]
    Duration of Objective Response, as Determined by Investigator Using RECIST Version 1.1

  11. Overall survival assessed from the start of study treatment to death for dose expansion as monotherapy (phase 2a) and in combination (phase 2b) [ Time Frame: From the start of study treatment until death due to any cause, assessed up to 36 months after the last subject's first treatment in the trial. ]
    Overall Survival

  12. Incidence of Adverse Events and Serious Adverse Events as assessed by NCI CTCAE V5.0 for dose expansion as monotherapy (phase 2a) and in combination (phase 2b) [ 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. ]
    Percentage of Subjects with Adverse Events and Serious Adverse Events



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Phase 1a:

• Subjects with non-CNS solid tumors that is metastatic or unresectable and for whom there is no available standard therapy.

Phase 2a:

• 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

Phase 1b/Phase 2:

  • 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 and tumor demonstrating PD-L1 expression in ≥1% of tumor cells (TPS ≥1%).
  • Subjects with recurrent or metastatic HNSCC with no prior systemic therapy administered in the recurrent or metastatic setting and tumor demonstrating PD-L1 IHC CPS ≥1.
  • Subjects with confirmed metastatic PDAC with no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease.

General (all phases):

Dose Escalation and Expansion:

  • Must be age ≥ 18 years of age
  • Measurable disease according to RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) 0-1
  • Normal or adequate liver, renal, cardiac and bone marrow function

Exclusion Criteria:

Phase 1a/Phase 2a

  • 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

Phase 1b/Phase 2

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04083599


Contacts
Layout table for location contacts
Contact: Genmab A/S Trial Information +4570202728 ext +4570202728 clinicaltrials@genmab.com

Locations
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United States, Connecticut
Yale University Cancer Center Recruiting
New Haven, Connecticut, United States, 06520
Principal Investigator: Patricia LoRusso         
United States, North Carolina
Levine Cancer Center Recruiting
Charlotte, North Carolina, United States, 28204
Principal Investigator: Daniel Haggstrom         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Principal Investigator: Crystal Denlinger         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: cann.researchreferrals@scresearch.net         
Principal Investigator: Melissa Johnson         
Denmark
Rigshospitalet (Copenhagen University Hospital) Recruiting
Copenhagen, Denmark
Principal Investigator: Kristoffer Rohrberg         
Germany
Klinikum der Stadt Ludwigshafen am Rhein gGmbH Not yet recruiting
Ludwigshafen, Germany
Contact: E Dippel         
Department of Dermatology, University of Mainz Not yet recruiting
Mainz, Germany
Contact: C Loquai         
Universitätsmedizin Mannheim Dermatologie Not yet recruiting
Mannheim, Germany
Contact: J Utikal         
Universitaetsklinikum Wuerzburg Not yet recruiting
Wuerzburg, Germany
Contact: A Gesierich         
Spain
H. Vall d'Hebron Recruiting
Barcelona, Spain
Contact: E Felip         
HM CIOCC Hospital Universitario HM Sanchinarro Recruiting
Madrid, Spain
Contact: M De Miguel Luken         
MD Anderson Cancer Center Madrid Recruiting
Madrid, Spain
Contact: E Grande         
START Madrid - Hospital Universitario Fundacion Jimenez Diaz Recruiting
Madrid, Spain
Contact: V Moreno         
Clinica Universidad de Navarra Recruiting
Pamplona, Spain
Contact: I Melero         
United Kingdom
Royal Marsden NHS Foundation Trust Recruiting
Sutton, United Kingdom
Principal Investigator: Dr. Juanita Lopez         
Sponsors and Collaborators
Genmab
BioNTech SE
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Responsible Party: Genmab
ClinicalTrials.gov Identifier: NCT04083599    
Other Study ID Numbers: GCT1042-01
First Posted: September 10, 2019    Key Record Dates
Last Update Posted: October 1, 2021
Last Verified: September 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Squamous Cell Carcinoma of Head and Neck
Neoplasms by Site
Neoplasms by Histologic Type
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Head and Neck Neoplasms
Gemcitabine
Paclitaxel
Carboplatin
Pembrolizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological