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

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04083599
• Other study ID #: GCT1042-01
• Secondary ID: 2018-003716-47IR
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 17, 2019
• Est. completion date: October 2025

Study information

• Verified date: June 2024
• Source: Genmab
• Contact: Genmab A/S Trial Information
• Phone: +4570202728
• Email: clinicaltrials[@]genmab.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1287
• Est. completion date: October 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Biological:
• GEN1042
Intravenous

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

Locations

Country	Name	City	State
Denmark	Rigshospitalet (Copenhagen University Hospital)	Copenhagen
Denmark	Herlev University Hospital	Herlev
Denmark	University Hospital of Southern Denmark, Vejle Hospital	Vejle
France	Centre hospitalier Universitaire de Bordeaux	Bordeaux
France	Centre Antoine Lacassagne	Nice
France	Gustave Roussy	Villejuif
Georgia	ARENSIA Research Clinic at the Research Institute of Clinical Medicine	Tbilisi
Germany	Nationales Centrum fr Tumorerkrankungen NCT	Heidelberg
Germany	Klinikum der Stadt Ludwigshafen am Rhein gGmbH	Ludwigshafen
Germany	Department of Dermatology, University of Mainz	Mainz
Germany	Universitätsmedizin Mannheim Dermatologie	Mannheim
Germany	Universitaetsklinikum Wuerzburg	Wuerzburg
Israel	Rabin Medical Center	Petah tikva
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliera Spedali Civili di Brescia	Brescia
Italy	Azienda Ospedaliera S.Croce e Carle Cuneo	Cuneo
Italy	Istituto Nazionale dei Tumori	Milan
Italy	Istituto Clinico Humanitas	Rozzano
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si
Korea, Republic of	Jeonbuk National University Hospital	Jeonju
Korea, Republic of	Gachon University Gil Medical Center	Namdong
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan
Moldova, Republic of	ARENSIA Research Clinic at the Oncology Institute	Chisinau
Spain	H. Vall d'Hebron	Barcelona
Spain	START Barcelona HM Nou Delfos	Barcelona
Spain	Hospital Duran i Reynals - ICO L Hospitalet	L'Hospitalet De Llobregat
Spain	Hospital Universitario Insular de Gran Canaria	Las Palmas De Gran Canaria
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Clinica Universidad de Navarra	Madrid
Spain	HM CIOCC Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Maran	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	MD Anderson Cancer Center Madrid	Madrid
Spain	START Madrid - Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Complejo Hospitalario Universitario de Santiago (CHUS)	Santiago De Compostela
Spain	Hospital Virgen del Rocio	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
Taiwan	Chang Gung Memorial Hospital (CGMH) - Kaohsiung Branch	Kaohsiung City
Taiwan	Kaohsiung Medical University Memorial Hospital	Kaohsiung City
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Taipei Medical University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital, VGHTPE	Taipei
Taiwan	Chang Gung Memorial Hospital Linkou Branch	Taoyuan
United Kingdom	Royal Marsden NHS Foundation Trust	Sutton
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Levine Cancer Center	Charlotte	North Carolina
United States	Maryland Oncology Hematology PA	Columbia	Maryland
United States	Virgina Cancer Specialists	Fairfax	Virginia
United States	Hope and Healing Cancer Services	Hinsdale	Illinois
United States	Lumi Research	Kingwood	Texas
United States	University of Kentucky	Lexington	Kentucky
United States	Cancer & Blood Specialty Clinic	Los Alamitos	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale University Cancer Center	New Haven	Connecticut
United States	ChristianaCare	Newark	Delaware
United States	Florida Cancer Affiliates	Ocala	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Kaiser Permanente (KP) Oncology/Hematology	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Moores Cancer Center at the UC San Diego Health	San Diego	California
United States	Adventist Health System/Sunbelt,Inc	Seattle	Washington
United States	Medical Oncology Associates, PS	Spokane	Washington
United States	Novant Health Cancer Institute - Forsyth (Medical Oncology)	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Genmab	BioNTech SE

Countries where clinical trial is conducted

United States,  Denmark,  France,  Georgia,  Germany,  Israel,  Italy,  Korea, Republic of,  Moldova, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects With Dose-Limiting Toxicities (DLT)	Occurrence of Dose-Limiting Toxicities (DLT) assessed by the Investigator	First Cycle (21 days)
Primary	Objective Response Rate (ORR)	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.	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)
Secondary	Percentage of Subjects with Adverse Events and Serious Adverse Events	Incidence of Adverse Events and Serious Adverse Events as assessed by NCI CTCAE V5.0	Baseline up to 90 Days After the Last Dose, assessed up to 36 months after the last subject's first treatment in the trial.
Secondary	Duration of Object Response (DOR)	Defined as time from the first documentation of objective response (CR or PR) to the date of first PD or death.	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)
Secondary	Disease Control Rate (DCR)	Determined by Investigator Using RECIST Version 1.1	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)
Secondary	Progression-Free Survival (PFS)	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.	From the start of the study treatment until disease progression/death whichever occurs first. (an expected average of 10 months)
Secondary	Overall survival (OS)	Defined as the time from start of study treatment to date of death due to any cause.	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.
Secondary	Dose Escalation: Maximum Concentration (Cmax) of GEN1042	Pharmacokinetic (PK) parameters of GEN1042, and incidence of anti-drug antibodies Dose Escalation: Maximum Concentration (Cmax) of GEN1042	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)
Secondary	Dose Escalation: Area Under the Concentration Time Curve (AUC) of GEN1042	Pharmacokinetic (PK) parameters of GEN1042, and incidence of anti-drug antibodies Dose Escalation: Area Under the Concentration Time Curve (AUC) of GEN1042	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)
Secondary	Dose Escalation: Half-life (t1/2) of GEN1042	Dose Escalation: Half-life (t1/2) of GEN1042	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)
Secondary	Dose Expansion: Area Under the Concentration Time Curve (AUC) of GEN1042	Dose Expansion: Area Under the Concentration Time Curve (AUC) of GEN1042	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)
Secondary	Dose Expansion: Maximum Concentration (Cmax) of GEN1042	Dose Expansion: Maximum Concentration (Cmax) of GEN1042	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)
Secondary	Dose Escalation: Incidence of ADA response to GEN1042	Dose Escalation: Incidence of ADA response to GEN1042responses to GEN1042	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)
Secondary	Dose Expansion: Incidence of ADA response to GEN1042	Dose Expansion: Incidence of ADA response to GEN1042	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)