GEN1042 Safety Trial and Anti-tumor Activity in Subjects With Malignant Solid Tumors
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| ClinicalTrials.gov Identifier: NCT04083599 |
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Recruitment Status :
Recruiting
First Posted : September 10, 2019
Last Update Posted : December 28, 2022
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Sponsor:
Genmab
Collaborator:
BioNTech SE
Information provided by (Responsible Party):
Genmab
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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 Drug: Pemetrexed Drug: Paclitaxel | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 647 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 : | October 2025 |
| Estimated Study Completion Date : | October 2025 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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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).
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Biological: GEN1042
Intravenous |
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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.
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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 |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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
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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
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 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):
- 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
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.
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
| Contact: Genmab A/S Trial Information | +4570202728 | clinicaltrials@genmab.com |
Locations
Show 28 study locations
Sponsors and Collaborators
Genmab
BioNTech SE
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Genmab |
| ClinicalTrials.gov Identifier: | NCT04083599 |
| Other Study ID Numbers: |
GCT1042-01 2018-003716-47 ( EudraCT Number ) |
| First Posted: | September 10, 2019 Key Record Dates |
| Last Update Posted: | December 28, 2022 |
| Last Verified: | December 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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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 Albumin-Bound Paclitaxel Carboplatin Pembrolizumab Pemetrexed 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 Folic Acid Antagonists |