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

Genmab

Status and phase: Enrolling; Phase 2; Phase 1

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

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT04083599

2023-508526-10-00 (Registry Identifier)

IRAS ID: 263292 (Registry Identifier)

2018-003716-47 (EudraCT Number)

GCT1042-01

MOH_2023-07-31_012855 (Registry Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment: 1,287 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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1,287 participants in 2 patient groups

Monotherapy - Dose Escalation and Dose Expansion parts

Experimental group

Description:

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).

Treatment:

Biological: GEN1042

Combination Therapy - Dose Expansion Part

Experimental group

Description:

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.

Treatment:

Drug: Gemcitabine

Drug: Carboplatin

Drug: Paclitaxel

Drug: Pemetrexed

Drug: 5-FU

Drug: Nab paclitaxel

Drug: Pembrolizumab

Biological: GEN1042

Drug: Cisplatin