GEN1046 Safety Trial in Patients With Malignant Solid Tumors

Non-small Cell Lung Cancer Clinical Trial

Official title:

First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1046 in Subjects With Malignant Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03917381
• Other study ID #: GCT1046-01
• Secondary ID: 2018-003402-63MO
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 14, 2019
• Est. completion date: October 2025

Study information

• Verified date: June 2024
• Source: Genmab
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the trial is to evaluate the safety of acasunlimab (also known as GEN1046) as monotherapy and in combination therapies in patients with malignant solid tumors

Description:

The trial is an open-label, multi-center safety trial of acasunlimab (GEN1046). The trial consists of two parts, a dose escalation part (phase 1, first-in-human (FIH) and an expansion part (phase 2a)). The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) has been determined.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 429
• Est. completion date: October 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

For Dose Escalation:

• Have a histologically or cytologically confirmed non-CNS solid tumor that is metastatic or unresectable and for whom there is no available standard therapy

For Expansion:

• Have histologically or cytological confirmed diagnosis of relapsed or refractory, advanced and/or metastatic NSCLC, EC, UC, TNBC, SCCHN, or cervical cancer who are not anymore candidates for standard therapy For separate expansion cohorts: metastatic NSCLC without prior systemic treatment regimens for metastatic disease.

For Both Dose Escalation and Expansion

• Have measurable disease according to RECIST 1.1

• Have Eastern Cooperative Oncology Group (ECOG) 0-1

• Have an acceptable hematological status

• Have acceptable liver function

• Have an acceptable coagulation status

• Have acceptable renal function

Key Exclusion Criteria:

• Have uncontrolled intercurrent illness, including but not limited to:

• Ongoing or active infection requiring intravenous treatment with anti-infective therapy, or any ongoing systemic inflammatory condition requiring further diagnostic work-up or management during screening.

• Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia

• Uncontrolled hypertension defined as systolic blood pressure = 160 mmHg and/or diastolic blood pressure = 100 mmHg, despite optimal medical management

• Ongoing or recent evidence of autoimmune disease

• History of irAEs that led to prior checkpoint treatment discontinuation

• Prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade

• History of chronic liver disease or evidence of hepatic cirrhosis

• History of non-infectious pneumonitis that has required steroids or currently has pneumonitis

• History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of acasunlimab

• Serious, non-healing wound, skin ulcer (of any grade), or bone fracture

• Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new (younger than 6 months) or progressive brain metastases or stroke

• Prior therapy:

• Radiotherapy within 14 days prior to first dose of acasunlimab. Note: palliative radiotherapy will be allowed.

• Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to acasunlimab administration. Accepted exceptions are bisphosphonates (e.g., pamidronate, zoledronic acid, etc.) and denosumab

• Toxicities from previous anti-cancer therapies that have not adequately resolved

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Carcinoma
• Cervical Cancer
• Endometrial Carcinoma
• Endometrial Neoplasms
• Non-small Cell Lung Cancer
• Solid Tumors
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms
• Urothelial Carcinoma

Intervention

Biological:
• Acasunlimab
Acasunlimab will be administered intravenously once every 21 days (in selected expansion cohorts acasunlimab will be administered intravenously once every 21 days for the first 2 cycles, and every 42 days in subsequent cycles)
• Acasunlimab in combination with docetaxel (in a single expansion cohort)
Acasunlimab and docetaxel will be administered intravenously once every 21 days
• Acasunlimab in combination with pembrolizumab (in a separate expansion cohort)
Acasunlimab and pembrolizumab will be administered intravenously once every 21 days or every 42 days, respectively
• Acasunlimab in combination with pembrolizumab and standard chemotherapy (in separate expansion cohorts)
Acasunlimab and pembrolizumab and standard chemotherapy will be administered intravenously once every 21 days for 4 cycles, followed by treatment with acasunlimab and pembrolizumab once every 21 days

Locations

Country	Name	City	State
Czechia	Fakultni nemocnice Brno	Brno
Czechia	University Hospital Brno	Brno
Czechia	Nemocnice AGEL Ostrava-Vítkovice a.s.	Nový Jicín
Czechia	Fakultni nemocnice Olomouc	Olomouc
Georgia	High Technology Hospital Medcenter	Batumi
Georgia	LLC "TIM - Tbilisi Institute of Medicine"	Tbilisi
Georgia	LTD Consilium Medulla	Tbilisi
Georgia	Tbilisi State Medical University and Ingorovka High Medical Technology University Clinic Ltd	Tbilisi
Hungary	Onkologiai Klinika	Debrecen
Hungary	BKMK Hospital	Kecskemét
Hungary	Pulmonology Hospital Törökbálinti	Törökbálint
Israel	Rambam Health Care Campus RHCC - Rambam Medical Center	Haifa
Israel	Hadassah Medical Organization HMO - Sharett Institute of Oncology	Jerusalem
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	Sheba Medical Center, Ramat Gan	Tel HaShomer
Italy	Policlinico San'Orsola	Bologna
Italy	IRCCS - Istituto Europeo di Oncologia IEO	Milan
Italy	Istituto Nazionale Tumori - Fondazione Pascale Italy	Napoli
Italy	Azienda Ospedaliero Universitaria di Parma	Parma
Italy	AUSL Romagno-Ravenna	Ravenna
Italy	Policlinico Uni. Campus Bio-Medico	Roma
Italy	Regina Elena National Cancer Institute	Rome
Italy	ASST Sette Laghi "Ospedale di Circolo e Fondazione Macchi "	Varese
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Medpolonia Sp. z o.o.	Poznan
Poland	Specialist Hospital in Prabuty	Prabuty
Poland	Dom Lekarski SA	Szczecin
Poland	Maria Sklodowska Curie National Research Instutute of Oncology	Warsaw
Spain	Hospital Universitario Vall dHebron	Barcelona
Spain	IOB-Hospital Quironsalud Barcelona	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	MD Anderson Cancer Center Madrid	Madrid
Spain	NEXT Oncology Madrid	Madrid
Spain	START Madrid-CIOCC	Madrid
Spain	START Madrid-FJD, Hospital Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Hospital Clinico De Valencia	Valencia
Turkey	Gulhane Training and Research Hospital	Ankara
Turkey	Trakya University Hospital	Edirne
Turkey	Medical Point Izmir Hospital	Karsiyaka
Ukraine	ARENSIA Exploratory Medicine LLC	Kyiv
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	UNC Chapel Hill	Chapel Hill	North Carolina
United States	Levine Cancer Institute, Atrium Health	Charlotte	North Carolina
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	START Midwest	Grand Rapids	Michigan
United States	University of Iowa Hospitals	Iowa City	Iowa
United States	Mayo Clinic	Jacksonville	Florida
United States	Norton Healthcare Inc	Louisville	Kentucky
United States	Yale University Cancer Center	New Haven	Connecticut
United States	NYU Langone	New York	New York
United States	Mayo Clinic	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Genmab	BioNTech SE

Countries where clinical trial is conducted

United States,  Czechia,  Georgia,  Hungary,  Israel,  Italy,  Poland,  Spain,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity (DLT)	to determine maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)	DLTs are assessed during the first cycle (21 days) in each cohort]
Primary	Adverse events	Incidence of treatment-emergent adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0	throughout the study and until end of safety follow-up period (60 days after last dose)
Primary	Safety laboratory parameters (hematology, biochemistry, coagulation, endocrines)	Laboratory parameters graded by CTCAE v5.0	throughout the study and until end of safety follow-up period (60 days after last dose)
Primary	For expansion cohort 1 only: Objective Response Rate (ORR)	Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by Independent Review Committee (IRC)	throughout the study until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 6 months)
Secondary	PK parameters	Total body clearance of drug from the plasma	throughout the study and until end of safety follow-up period (60 days after last dose)
Secondary	PK parameters	Volume of distribution	throughout the study and until end of safety follow-up period (60 days after last dose)
Secondary	PK parameters	The area under the curve (AUC) from time zero to day 21	throughout the study and until end of safety follow-up period (60 days after last dose)
Secondary	PK parameters	The AUC from time zero to infinity	throughout the study and until end of safety follow-up period (60 days after last dose)
Secondary	PK parameters	The AUC from time zero to last quantifiable measurement	throughout the study and until end of safety follow-up period (60 days after last dose)
Secondary	PK parameters	The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration	throughout the study and until end of safety follow-up period (60 days after last dose)
Secondary	PK parameters	The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration	throughout the study and until end of safety follow-up period (60 days after last dose)
Secondary	PK parameters	The elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve	throughout the study and until end of safety follow-up period (60 days after last dose)
Secondary	Anti-Drug Antibody (ADA) response	Number of subjects with ADA response	throughout the study and until end of safety follow-up period (60 days after last dose)
Secondary	Objective Response Rate (ORR)	Rate of subjects with objective response assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	throughout the study until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 6 months)
Secondary	Disease Control Rate (DCR)	Rate of subjects with disease control assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	throughout the study until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 6 months)
Secondary	Duration of Response (DoR)	Duration of Response assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	throughout the study until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 6 months)
Secondary	Adverse events expansion, cohort 1 only	Incidence of treatment-emergent adverse events as assessed by CTCAE v5.0	throughout the study and until end of safety follow-up period (60 days after last dose)
Secondary	Laboratory parameters, cohort 1 only	Laboratory parameters graded by CTCAE v5.0 (Listing of all laboratory data with values flagged and shift tables)	throughout the study and until end of safety follow-up period (60 days after last dose)
Secondary	Duration of Response (DoR), cohort 1 only	Duration of Response assessed by independent review committee using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	throughout the study until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 6 months)
Secondary	Progression free survival (PFS), cohort 1 only	Progression free survival assessed by independent review committee and assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	throughout the study until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 6 months)
Secondary	Overall survival (OS), cohort 1 only	Overall survival	throughout the study until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 6 months)