GEN1046 Safety Trial in Patients With Malignant Solid Tumors
- Conditions
- Urothelial CarcinomaSolid TumorsSquamous Cell Carcinoma of the Head and NeckNon-small Cell Lung CancerTriple Negative Breast CancerCervical CancerEndometrial Carcinoma
- Interventions
- Biological: Acasunlimab in combination with docetaxel (in a single expansion cohort)
- Registration Number
- NCT03917381
- Lead Sponsor
- Genmab
- Brief Summary
The goal of this trial is to learn about the antibody acasunlimab (an antibody also known as GEN1046) when it is used alone and when it is used together with standard of care treatment (docetaxel) or another antibody cancer drug, pembrolizumab (with or without chemotherapy), for treatment of patients with certain types of cancer. All subjects will receive active drug; no one will receive placebo.
This trial has 2 parts. The purpose of the first part is to find out if acasunlimab is safe and to find out the best doses of acasunlimab to use. The purpose of the second part is to give acasunlimab to more subjects to see how well the doses of acasunlimab selected in the first part work against cancer when given alone and how well they work when given with pembrolizumab (with or without other chemotherapy) or docetaxel.
Trial details include:
* The average trial duration for an individual subject will be about 74 weeks.
* The average treatment duration for an individual subject will be about 21 weeks.
* The visit frequency will be weekly at first and lessening over time until visits are only once every 3 weeks.
- Detailed 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 & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 429
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
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation Acasunlimab Acasunlimab will be administered as monotherapy. Expansion Acasunlimab Acasunlimab will be administered as monotherapy or in combination with either docetaxel, pembrolizumab, or pembrolizumab + standard chemotherapy in separate expansion cohorts. Expansion Acasunlimab in combination with docetaxel (in a single expansion cohort) Acasunlimab will be administered as monotherapy or in combination with either docetaxel, pembrolizumab, or pembrolizumab + standard chemotherapy in separate expansion cohorts. Expansion Acasunlimab in combination with pembrolizumab (in a separate expansion cohort) Acasunlimab will be administered as monotherapy or in combination with either docetaxel, pembrolizumab, or pembrolizumab + standard chemotherapy in separate expansion cohorts. Expansion Acasunlimab in combination with pembrolizumab and standard chemotherapy (in separate expansion cohorts) Acasunlimab will be administered as monotherapy or in combination with either docetaxel, pembrolizumab, or pembrolizumab + standard chemotherapy in separate expansion cohorts.
- Primary Outcome Measures
Name Time Method Dose Escalation: Number of Participants With Dose Limiting Toxicity (DLT) During first cycle (21 days) for each cohort Toxicities will be graded for severity according to Common Terminology Criteria for Adverse Events (CTCAE) criteria version 5.0.
Dose Escalation and Monotherapy Expansion Cohorts: Number of Participants With Adverse Events (AEs) From first dose until the end of the study (up to 60 days after the last dose) Dose Escalation and Monotherapy Expansion Cohorts: Number of Participants With Shifts From Baseline in Safety Laboratory Parameters From first dose until the end of the study (up to 60 days after the last dose) Expansion Cohort 1: Objective Response Rate (ORR) Up to 3 years ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on response evaluation criteria in solid tumours (RECIST).
- Secondary Outcome Measures
Name Time Method Expansion Cohort 1: Number of Participants With AEs From first dose until the end of the study (up to 60 days after the last dose) Expansion Cohort 1: Number of Participants With Shifts From Baseline in Safety Laboratory Parameters From first dose until the end of the study (up to 60 days after the last dose) Combination Therapy Expansion Cohorts: Number of Participants With AEs From first dose until the end of the study (up to 60 days after the last dose) Combination Therapy Expansion Cohorts: Number of Participants With Shifts From Baseline in Safety Laboratory Parameters From first dose until the end of the study (up to 60 days after the last dose) All Parts: Total Body Clearance (CL) of GEN1046 Predose and postdose at multiple timepoints up to end of safety follow up (up to 60 days after last dose) All Parts: Volume of Distribution (Vd) of GEN1046 Predose and postdose at multiple timepoints up to end of safety follow up (up to 60 days after last dose) All Parts: Area Under the Concentration-Time Curve from Time Zero to Day 21 (AUC21days) of GEN1046 Predose and postdose at multiple timepoints for 21 days up to end of safety follow up (up to 60 days after last dose) All Parts: Area Under the Concentration-Time Curve from Time Zero to Infinity (AUCinf) of GEN1046 Predose and postdose at multiple timepoints up to end of safety follow up (up to 60 days after last dose) All Parts: Area Under the Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUClast) of GEN1046 Predose and postdose at multiple timepoints up to end of safety follow up (up to 60 days after last dose) All Parts: Maximum Observed Plasma Concentration (Cmax) of GEN1046 Predose and postdose at multiple timepoints up to end of safety follow up (up to 60 days after last dose) All Parts: Time to Reach Cmax (Tmax) of GEN1046 Predose and postdose at multiple timepoints up to end of safety follow up (up to 60 days after last dose) All Parts: Elimination Half-life (t½) of GEN1046 Predose and postdose at multiple timepoints up to end of safety follow up (up to 60 days after last dose) All Parts: Number of Participants with Anti-drug Antibodies (ADAs) Up to 3 years Venous blood samples will be collected for measurement of serum concentrations of ADAs.
Dose Escalation and Expansion Cohorts 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13: ORR Up to 3 years ORR is defined as the percentage of participants with BOR of CR or PR based on RECIST v1.1.
Dose Escalation and Expansion Cohorts 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13: Disease Control Rate (DCR) Up to 3 years The DCR is defined as the percentage of participants with confirmed BOR of CR, PR, or Stable Disease (SD) according to RECIST v1.1.
All Parts: Duration of Response (DoR) Up to 3 years DOR is defined as the time from first documentation of response (CR or PR) to the date of the first documented progression or death whichever occurs earlier based on RECIST v1.1.
Expansion Cohort 1: Progression Free Survival (PFS) Up to 3 years PFS is defined as the number of days from Day 1 in Cycle 1 to the first documented progression or death due to any cause, whichever occurs first based on RECIST version 1.1.
Expansion Cohort 1: Overall survival (OS) Up to 3 years OS is defined as the number of days from Day 1 in Cycle 1 to death due to any cause.
Trial Locations
- Locations (55)
LTD Consilium Medulla
🇬🇪Tbilisi, Georgia
IOB-Hospital Quironsalud Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Medical Point Izmir Hospital
🇹🇷Karsiyaka, Turkey
University of Iowa Hospitals
🇺🇸Iowa City, Iowa, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Levine Cancer Institute, Atrium Health
🇺🇸Charlotte, North Carolina, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
NYU Langone
🇺🇸New York, New York, United States
University Hospital Brno
🇨🇿Brno, Czechia
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
LLC "TIM - Tbilisi Institute of Medicine"
🇬🇪Tbilisi, Georgia
Nemocnice AGEL Ostrava-Vítkovice a.s.
🇨🇿Nový Jičín, Czechia
Onkologiai Klinika
🇭🇺Debrecen, Hungary
High Technology Hospital Medcenter
🇬🇪Batumi, Georgia
Tbilisi State Medical University and Ingorovka High Medical Technology University Clinic Ltd
🇬🇪Tbilisi, Georgia
BKMK Hospital
🇭🇺Kecskemét, Hungary
Pulmonology Hospital Törökbálinti
🇭🇺Törökbálint, Hungary
Rambam Health Care Campus RHCC - Rambam Medical Center
🇮🇱Haifa, Israel
Hadassah Medical Organization HMO - Sharett Institute of Oncology
🇮🇱Jerusalem, Israel
Policlinico San'Orsola
🇮🇹Bologna, Italy
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
IRCCS - Istituto Europeo di Oncologia IEO
🇮🇹Milan, Italy
Istituto Nazionale Tumori - Fondazione Pascale Italy
🇮🇹Napoli, Italy
Sheba Medical Center, Ramat Gan
🇮🇱Tel HaShomer, Israel
Azienda Ospedaliero Universitaria di Parma
🇮🇹Parma, Italy
Regina Elena National Cancer Institute
🇮🇹Rome, Italy
AUSL Romagno-Ravenna
🇮🇹Ravenna, Italy
Policlinico Uni. Campus Bio-Medico
🇮🇹Roma, Italy
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdańsk, Poland
ASST Sette Laghi "Ospedale di Circolo e Fondazione Macchi "
🇮🇹Varese, Italy
Specialist Hospital in Prabuty
🇵🇱Prabuty, Poland
Medpolonia Sp. z o.o.
🇵🇱Poznań, Poland
Maria Sklodowska Curie National Research Instutute of Oncology
🇵🇱Warsaw, Poland
Dom Lekarski SA
🇵🇱Szczecin, Poland
Hospital Universitario Vall dHebron
🇪🇸Barcelona, Spain
START Madrid-FJD, Hospital Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
START Madrid-CIOCC
🇪🇸Madrid, Spain
MD Anderson Cancer Center Madrid
🇪🇸Madrid, Spain
NEXT Oncology Madrid
🇪🇸Madrid, Spain
Hospital Universitario La Princesa
🇪🇸Madrid, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
Hospital Clinico De Valencia
🇪🇸Valencia, Spain
Trakya University Hospital
🇹🇷Edirne, Turkey
ARENSIA Exploratory Medicine LLC
🇺🇦Kyiv, Ukraine
Gulhane Training and Research Hospital
🇹🇷Ankara, Turkey
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Yale University Cancer Center
🇺🇸New Haven, Connecticut, United States
Norton Healthcare Inc
🇺🇸Louisville, Kentucky, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
UNC Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States