Trial record 1 of 1 for:
GCT-1046-01
GEN1046 Safety Trial in Patients With Malignant Solid Tumors
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| ClinicalTrials.gov Identifier: NCT03917381 |
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Recruitment Status :
Active, not recruiting
First Posted : April 17, 2019
Last Update Posted : April 3, 2024
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Sponsor:
Genmab
Collaborator:
BioNTech SE
Information provided by (Responsible Party):
Genmab
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Brief 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
| 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: Acasunlimab Biological: Acasunlimab in combination with docetaxel (in a single expansion cohort) Biological: Acasunlimab in combination with pembrolizumab (in a separate expansion cohort) Biological: Acasunlimab in combination with pembrolizumab and standard chemotherapy (in separate expansion cohorts) | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 429 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
MedlinePlus Genetics related topics:
Breast cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose escalation
Acasunlimab will be administered as monotherapy
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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)
Other Names:
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Experimental: Expansion
Acasunlimab 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)
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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)
Other Names:
Biological: Acasunlimab in combination with docetaxel (in a single expansion cohort) Acasunlimab and docetaxel will be administered intravenously once every 21 days
Other Names:
Biological: 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
Other Names:
Biological: 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
Other Names:
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Primary Outcome Measures :
- 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)
- 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
- 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
- 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 :
- 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
- PK parameters [ Time Frame: throughout the study and until end of safety follow-up period (60 days after last dose) ]Volume of distribution
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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)
- 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
- 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
- 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
Information from the National Library of Medicine
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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:
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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
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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.
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
Locations
Show 57 study locations
Sponsors and Collaborators
Genmab
BioNTech SE
Investigators
| Study Director: | Study Official | Genmab |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Genmab |
| ClinicalTrials.gov Identifier: | NCT03917381 |
| Other Study ID Numbers: |
GCT1046-01 2018-003402-63 ( EudraCT Number ) MOH_2019-05-08_006011 ( Registry Identifier: Clinical Research Site - mytrial ) |
| First Posted: | April 17, 2019 Key Record Dates |
| Last Update Posted: | April 3, 2024 |
| Last Verified: | April 2024 |
| 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 |