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GEN1046 Safety Trial in Patients With Malignant Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03917381
Recruitment Status : Recruiting
First Posted : April 17, 2019
Last Update Posted : December 27, 2022
Sponsor:
Collaborator:
BioNTech SE
Information provided by (Responsible Party):
Genmab

Study Description
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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) Biological: GEN1046 in combination with pembrolizumab and standard chemotherapy (in separate expansion cohorts) 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
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 752 participants
Allocation: N/A
Intervention Model: Sequential Assignment
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
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose escalation
GEN1046 Open label, single arm trial where GEN1046 will be administered as monotherapy
 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)
Experimental: Expansion
GEN1046 Open label, single arm trial where GEN1046 will be administered as monotherapy (or in combination with docetaxel or in combination with pembrolizumab or in combination with pembrolizumab and standard chemotherapy 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

Biological: GEN1046 in combination with pembrolizumab and standard chemotherapy (in separate expansion cohorts)
GEN1046 and pembrolizumab and standard chemotherapy will be administered intravenously once every 21 days for 4 cycles, followed by treatment with GEN1046 and pembrolizumab once every 21 days


Outcome Measures
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Primary Outcome Measures :
  1. Dose limiting toxicity (DLT) [ Time Frame: 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)

  2. Adverse events [ Time Frame: throughout the study and until end of safety follow-up period (60 days after last dose) ]
    Incidence of treatment-emergent adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  3. Safety laboratory parameters (hematology, biochemistry, coagulation, endocrines) [ Time Frame: throughout the study and until end of safety follow-up period (60 days after last dose) ]
    Laboratory parameters graded by CTCAE v5.0

  4. For expansion cohort 1 only: Objective Response Rate (ORR) [ Time Frame: 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) ]
    Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by Independent Review Committee (IRC)


Secondary Outcome Measures :
  1. PK parameters [ Time Frame: throughout the study and until end of safety follow-up period (60 days after last dose) ]
    Total body clearance of drug from the plasma

  2. PK parameters [ Time Frame: throughout the study and until end of safety follow-up period (60 days after last dose) ]
    Volume of distribution

  3. PK parameters [ Time Frame: throughout the study and until end of safety follow-up period (60 days after last dose) ]
    The area under the curve (AUC) from time zero to day 21

  4. PK parameters [ Time Frame: throughout the study and until end of safety follow-up period (60 days after last dose) ]
    The AUC from time zero to infinity

  5. PK parameters [ Time Frame: throughout the study and until end of safety follow-up period (60 days after last dose) ]
    The AUC from time zero to last quantifiable measurement

  6. PK parameters [ Time Frame: throughout the study and until end of safety follow-up period (60 days after last dose) ]
    The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration

  7. PK parameters [ Time Frame: throughout the study and until end of safety follow-up period (60 days after last dose) ]
    The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration

  8. PK parameters [ Time Frame: throughout the study and until end of safety follow-up period (60 days after last dose) ]
    The elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve

  9. Anti-Drug Antibody (ADA) response [ Time Frame: throughout the study and until end of safety follow-up period (60 days after last dose) ]
    Number of subjects with ADA response

  10. Objective Response Rate (ORR) [ Time Frame: 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) ]
    Rate of subjects with objective response assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  11. Disease Control Rate (DCR) [ Time Frame: 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) ]
    Rate of subjects with disease control assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  12. Duration of Response (DoR) [ Time Frame: 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) ]
    Duration of Response assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  13. Adverse events expansion, cohort 1 only [ Time Frame: throughout the study and until end of safety follow-up period (60 days after last dose) ]
    Incidence of treatment-emergent adverse events as assessed by CTCAE v5.0

  14. Laboratory parameters, cohort 1 only [ Time Frame: throughout the study and until end of safety follow-up period (60 days after last dose) ]
    Laboratory parameters graded by CTCAE v5.0 (Listing of all laboratory data with values flagged and shift tables)

  15. Duration of Response (DoR), cohort 1 only [ Time Frame: 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) ]
    Duration of Response assessed by independent review committee using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  16. Progression free survival (PFS), cohort 1 only [ Time Frame: 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) ]
    Progression free survival assessed by independent review committee and assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  17. Overall survival (OS), cohort 1 only [ Time Frame: 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) ]
    Overall survival


Eligibility Criteria
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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:

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 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
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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): NCT03917381


Contacts
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Contact: Genmab Trial Information +4570202728 clinicaltrials@genmab.com

Locations
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Sponsors and Collaborators
Genmab
BioNTech SE
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Genmab
ClinicalTrials.gov Identifier: NCT03917381    
Other Study ID Numbers: GCT1046-01
2018-003402-63 ( EudraCT Number )
First Posted: April 17, 2019    Key Record Dates
Last Update Posted: December 27, 2022
Last Verified: December 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Carcinoma
Triple Negative Breast Neoplasms
Squamous Cell Carcinoma of Head and Neck
Endometrial Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Carcinoma, Squamous Cell
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Diseases
Genital Diseases, Female
Female Urogenital Diseases
 Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Genital Diseases
Breast Neoplasms
Breast Diseases
Skin Diseases
Head and Neck Neoplasms
Docetaxel
Pembrolizumab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological