GEN1046 Safety Trial in Patients With Malignant Solid Tumors

Sponsor

Genmab (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03917381

Collaborator

BioNTech SE (Industry)

572

Enrollment

Locations

Arm

54.6

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors Non-small Cell Lung Cancer Urothelial Carcinoma Endometrial Carcinoma Triple Negative Breast Cancer Squamous Cell Carcinoma of the Head and Neck Cervical Cancer	Biological: GEN1046 Biological: GEN1046 in combination with docetaxel (in a single expansion cohort) Biological: GEN1046 in combination with pembrolizumab (in a separate expansion cohort)	Phase 1/Phase 2

Detailed Description

The trial is an open-label, multi-center safety trial of 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

572 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

The starting dose is administered as a flat dose. Dose escalation steps are based on safety dataThe starting dose is administered as a flat dose. Dose escalation steps are based on safety data

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 14, 2019

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm GEN1046 Open label, single arm trial where GEN1046 will be administered as monotherapy (or in combination with docetaxel or pembrolizumab in separate expansion cohorts)	Biological: GEN1046 GEN1046 will be administered intravenously once every 21 days (in selected expansion cohorts GEN1046 will be administered intravenously once every 21 days for the first 2 cycles, and every 42 days in subsequent cycles) Biological: GEN1046 in combination with docetaxel (in a single expansion cohort) GEN1046 and docetaxel will be administered intravenously once every 21 days. Biological: GEN1046 in combination with pembrolizumab (in a separate expansion cohort) GEN1046 and pembrolizumab will be administered intravenously once every 21 days or every 42 days, respectively

Arm

Intervention/Treatment

Experimental: Arm

GEN1046 Open label, single arm trial where GEN1046 will be administered as monotherapy (or in combination with docetaxel or pembrolizumab in separate expansion cohorts)

Biological: GEN1046

GEN1046 will be administered intravenously once every 21 days (in selected expansion cohorts GEN1046 will be administered intravenously once every 21 days for the first 2 cycles, and every 42 days in subsequent cycles)

Biological: GEN1046 in combination with docetaxel (in a single expansion cohort)

GEN1046 and docetaxel will be administered intravenously once every 21 days.

Biological: GEN1046 in combination with pembrolizumab (in a separate expansion cohort)

GEN1046 and pembrolizumab will be administered intravenously once every 21 days or every 42 days, respectively

Outcome Measures

Primary Outcome Measures

Dose limiting toxicity (DLT) [DLTs are assessed during the first cycle (21 days) in each cohort]]
to determine maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)
Adverse events [throughout the study and up to 2 months after last subject last treatment]
Incidence of treatment-emergent adverse events as assessed by CTCAE v5.0
Safety laboratory parameters (hematology, biochemistry, coagulation, endocrines) [throughout the study and up to 2 months after last subject last treatment]
Laboratory parameters graded by CTCAE v5.0
For expansion cohort 1 only: Objective Response Rate (ORR) [throughout the study and up to 2 months after last subject last treatment]
Objective Response Rate (ORR) per RECIST 1.1 assessed by Independent Review Committee (IRC)

Secondary Outcome Measures

Objective Response Rate (ORR) [throughout the study and up to 2 months after last subject last treatment]
Objective Response Rate (ORR) per RECIST 1.1 assessed by Independent Review Committee (IRC)
PK parameters [throughout the study and up to 2 months after last subject last treatment]
PK parameters
Anti-Drug Antibody (ADA) response [throughout the study and up to 2 months after last subject last treatment]
Anti-Drug Antibody (ADA) response
Anti-tumor activity, ie, reduction in tumor size according to RECIST 1.1 [throughout the study and up to 2 months after last subject last treatment]
Objective Response Rate (ORR) Disease Control Rate (DCR) Duration of Response (DoR)
For expansion cohort 1 only: Adverse events (AEs) [throughout the study and up to 2 months after last subject last treatment]
Adverse events (AEs)
For expansion cohort 1 only: Laboratory parameters [throughout the study and up to 2 months after last subject last treatment]
Laboratory parameters graded by CTCAE v5.0
For expansion cohort 1 only: Duration of response (DoR) [throughout the study and up to 2 months after last subject last treatment]
Duration of response (DoR), PFS per RECIST 1.1 assessed by IRC
For expansion cohort 1 only: ORR, DoR, PFS per RECIST 1.1 assessed by investigator [throughout the study and up to 2 months after last subject last treatment]
ORR, DoR, PFS per RECIST 1.1 assessed by investigator
For expansion cohort 1 only: Overall survival (OS) [throughout the study and up to 2 months after last subject last treatment]
Overall survival (OS)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 two 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 antiinfective therapy
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 GEN1046
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: Radiotherapy within 14 days prior to first GEN1046 administration. 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 GEN1046 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Phoenix	Arizona	United States	85054
2	Yale University Cancer Center	New Haven	Connecticut	United States	06520-8028
3	Mayo Clinic	Jacksonville	Florida	United States	32224
4	Emory University	Atlanta	Georgia	United States	30322
5	University of Iowa Hospitals	Iowa City	Iowa	United States	52242
6	Norton Healthcare Inc	Louisville	Kentucky	United States	40202
7	University of Michigan	Ann Arbor	Michigan	United States	48109
8	START Midwest	Grand Rapids	Michigan	United States	49546
9	Mayo Clinic	Rochester	Minnesota	United States	55905
10	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
11	NYU Langone	New York	New York	United States	10016
12	UNC Chapel Hill	Chapel Hill	North Carolina	United States	27514
13	Levine Cancer Institute, Atrium Health	Charlotte	North Carolina	United States	28204
14	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
15	University Hospital Brno	Brno		Czechia
16	Fakultni nemocnice Olomouc	Olomouc		Czechia
17	Onkologiai Klinika	Debrecen		Hungary
18	BKMK Hospital	Kecskemét		Hungary
19	Pulmonology Hospital Törökbálinti	Törökbálint		Hungary
20	Rambam Health Care Campus RHCC - Rambam Medical Center	Haifa		Israel
21	Hadassah Medical Organization HMO - Sharett Institute of Oncology	Jerusalem		Israel	12000
22	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239
23	Sheba Medical Center, Ramat Gan	Tel HaShomer		Israel	52621
24	IRCCS - Istituto Europeo di Oncologia IEO	Milan		Italy
25	Istituto Nazionale Tumori - Fondazione Pascale Italy	Napoli		Italy
26	AUSL Romagno-Ravenna	Ravenna		Italy
27	Policlinico Uni. Campus Bio-Medico	Roma		Italy
28	Regina Elena National Cancer Institute	Rome		Italy
29	Uniwersyteckie Centrum Kliniczne	Gdańsk		Poland
30	Dom Lekarski SA	Szczecin		Poland
31	Maria Sklodowska Curie National Research Instutute of Oncology	Warsaw		Poland
32	Medpolonia Sp. z o.o.	Wielkopolskie		Poland
33	Hospital Universitario Vall dHebron	Barcelona		Spain	08035
34	START Madrid-FJD, Hospital Fundación Jiménez Díaz	Madrid		Spain	28040
35	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
36	START Madrid-CIOCC	Madrid		Spain	28050
37	Hospital Universitario La Princesa	Madrid		Spain
38	MD Anderson Cancer Center Madrid	Madrid		Spain
39	Hospital Universitario Virgen de la Victoria	Málaga		Spain
40	Clinica Universidad de Navarra	Pamplona		Spain	31008
41	Hospital Clinico De Valencia	Valencia		Spain	46010