Phase 1a/1b Study of Aplitabart (IGM-8444) Alone or in Combination in Participants with Relapsed, Refractory, or Newly Diagnosed Cancers
- Conditions
- Acute Myeloid LeukemiaSarcomaChondrosarcomaChronic Lymphocytic LeukemiaColorectal CancerSolid TumorNon Hodgkin LymphomaSmall Lymphocytic Lymphoma
- Interventions
- Drug: Aplitabart (IGM-8444)Drug: FOLFIRI
- Registration Number
- NCT04553692
- Lead Sponsor
- IGM Biosciences, Inc.
- Brief Summary
This study is a first-in-human, Phase 1a/1b, multicenter, open-label study to determine the safety, tolerability, and pharmacokinetics of aplitabart as a single agent and in combination in participants with relapsed and/or refractory solid or hematologic cancers, as well as newly diagnosed cancers, and an open-label, randomized study of aplitabart+FOLFIRI+bevacizumab.
- Detailed Description
Participants will be enrolled in Phase 1a, which consists of two stages: a dose-escalation stage and an expansion stage. Aplitabart will be used as a single agent and in combination with numerous other agents where standard therapeutic regimens do not exist, have proven to be ineffective or intolerable, or are considered inappropriate.
Colorectal participants may be enrolled in Phase 1b, an open-label, randomized study of aplitabart+FOLFIRI+ bevacizumab.
Aplitabart will be investigated in numerous tumor types including all-comers solid tumors, colorectal carcinoma (CRC), sarcoma, non-Hodgkin's lymphoma (NHL), acute myeloid leukemia (AML), and chronic lymphocytic leukemia (CLL).
Aplitabart will be administered intravenously (IV).
An alternative dosing schedule may be evaluated.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 272
- Age ≥ 18 years at time of signing ICF
- ECOG Performance Status of 0 or 1
- Histologic documentation of incurable, locally advanced or metastatic tumor of the type being evaluated in individual cohorts.
- Adequate hepatic and renal function and adequate bone marrow reserve function.
- For combination cohorts, participants must be eligible to receive the chemotherapy or targeted agent.
- Ph1a only: No more than three prior therapeutic regimens.
- Ph1b only: Must be FOLFIRI naïve participants and must have received only 1 prior therapeutic regimen administered for the treatment of cancer in the advanced/metastatic setting - OR - FOLFIRI naïve participants that only received adjuvant therapy who progressed within six months after completing adjuvant therapy, and are confirmed to have locally advanced/metastatic disease
Key
- Inability to comply with study and follow-up procedures.
- Prior DR5 agonist therapy.
- Concomitant use of agents well-known to cause liver toxicity.
- Concomitant use of anti-cancer agents
- Palliative radiation to bone metastases within 2 weeks prior to Day 1.
- Major surgical procedure within 4 weeks prior to Day 1.
- Untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Participants with a history of treated CNS metastases are eligible.
- Prior use of any chemotherapeutic agent or small molecule inhibitors (SMI) within 2 weeks or 5 half-lives, prior to the first dose of study treatment
- Treatment with a monoclonal antibody, or any other anticancer agent (including biologic, experimental, or hormonal therapy) investigational or otherwise, that is not chemotherapy or a SMI, within 4 weeks or five half-lives prior to first dose of study treatment.
- Ph1b: Participants who have previously received FOLFIRI treatment in the adjuvant, advanced, or metastatic disease setting
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion Aplitabart (IGM-8444) Aplitabart will be administered intravenously in combination with FOLFIRI± bevacizumab. Ph1a: Aplitabart Single Agent Alternate Dosing Escalation Aplitabart (IGM-8444) Aplitabart will be administered intravenously as a single agent on an alternate dosing schedule. Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion Azacitidine Aplitabart will be administered intravenously in combination with Venetoclax and Azacitidine. Ph1b: Aplitabart + FOLFIRI + Bevacizumab Aplitabart (IGM-8444) Aplitabart will be administered intravenously in combination with FOLFIRI + bevacizumab Ph1b: Aplitabart + FOLFIRI + Bevacizumab FOLFIRI Aplitabart will be administered intravenously in combination with FOLFIRI + bevacizumab Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion Bevacizumab (and approved biosimilars) Aplitabart will be administered intravenously in combination with FOLFIRI± bevacizumab. Ph1a: Aplitabart + Birinapant Escalation and Expansion Birinapant Aplitabart will be administered intravenously in combination with Birinapant which will also be administered intravenously. Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion Gemcitabine Aplitabart will be administered intravenously in combination with Docetaxel and Gemcitabine. Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion Aplitabart (IGM-8444) Aplitabart will be administered intravenously in combination with Venetoclax and Azacitidine. Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion Venetoclax Aplitabart will be administered intravenously in combination with Venetoclax and Azacitidine. Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion FOLFIRI Aplitabart will be administered intravenously in combination with FOLFIRI± bevacizumab. Ph1a: Aplitabart + Birinapant Escalation and Expansion Aplitabart (IGM-8444) Aplitabart will be administered intravenously in combination with Birinapant which will also be administered intravenously. Ph1a: Aplitabart + Venetoclax Escalation and Expansion Aplitabart (IGM-8444) Aplitabart will be administered intravenously in combination with Venetoclax. Ph1b: FOLFIRI + Bevacizumab Bevacizumab (and approved biosimilars) Standard of Care FOLFIRI + bevacizumab will be administered intravenously Ph1a: Aplitabart + Venetoclax Escalation and Expansion Venetoclax Aplitabart will be administered intravenously in combination with Venetoclax. Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion Aplitabart (IGM-8444) Aplitabart will be administered intravenously in combination with Docetaxel and Gemcitabine. Ph1b: Aplitabart + FOLFIRI + Bevacizumab Bevacizumab (and approved biosimilars) Aplitabart will be administered intravenously in combination with FOLFIRI + bevacizumab Ph1b: FOLFIRI + Bevacizumab FOLFIRI Standard of Care FOLFIRI + bevacizumab will be administered intravenously Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion Docetaxel Aplitabart will be administered intravenously in combination with Docetaxel and Gemcitabine.
- Primary Outcome Measures
Name Time Method Ph1a: Adverse Events of aplitabart as single agent and with FOLFIRI ± bevacizumab, aplitibart with birinapant, aplitibart with venetoclax, aplitibart with venetoclax and azacitadine, and aplitibart with gemcitabine and docetaxel From Cycle 1 Day 1 through 28 days after the final dose of study drug Incidence of treatment-related AEs graded according to the NCI Common Technology Criteria for Adverse Events (CTCAE) v5.0
Ph1b: Progression-Free Survival (PFS) Study duration of approximately 36 months PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 by investigator or death, whichever occurs first.
Ph1a: To identify the recommended expansion dose for aplitabart as single agent, with FOLFIRI ± bevacizumab, aplitibart with birinapant, aplitibart with venetoclax, aplitibart with venetoclax and azacitadine, and aplitibart with gemcitabine and docetaxel 4 weeks Relationship between aplitabart dose and safety, PK, activity, and endpoints.
- Secondary Outcome Measures
Name Time Method Ph1b: Adverse events of aplitabart + FOLFIRI + bevacizumab From Cycle 1 Day 1 through 28 days after the final dose of study drug Incidence of treatment-related AEs graded according to the NCI Common Technology Criteria for Adverse Events (CTCAE) v5.0
Ph1a and Ph1b: Clearance (CL) of aplitabart At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months Clearance (CL) of aplitabart as a single agent and in combination with the anticancer agents listed above.
Ph1a and Ph1b: Area Under the Curve (AUC) of aplitabart At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months Area Under the Curve (AUC) of aplitabart as a single agent and in combination with the anticancer agents listed above.
Ph1a and Ph1b: Volume of distribution (V) of aplitabart At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months Volume of distribution (V) of aplitabart as a single agent and in combination with the anticancer agents listed above.
Ph1a and Ph1b: Maximum Concentration (c-max) of aplitabart At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months Maximum Concentration of aplitabart as a single agent and in combination with the anticancer agents listed above.
Ph1a and Ph1b: Immunogenicity through end of treatment at approximately 6 months Immunogenicity as assessed by detection of anti-drug antibodies (ADAs) to aplitabart
Ph1a and Ph1b: Objective Response Rate (ORR) Study duration of approximately 36 months Preliminary efficacy of objective response rate (ORR)
Ph1a and Ph1b: Duration of Response (DoR) Study duration of approximately 36 months Preliminary efficacy of duration of response (DoR)
Ph1a: Progression-Free Survival (PFS) Study duration of approximately 36 months PFS is defined as the time from first dose (Ph1a) to the first documented disease progression per RECIST 1.1 by investigator or death, whichever occurs first.
Ph1a and Ph1b: Overall Survival (OS) Study duration of approximately 36 months OS is defined as the time from first dose (Ph1a) or randomization (Ph1b) to death due to any cause
Trial Locations
- Locations (56)
Mayo Clinic
🇺🇸Minneapolis, Minnesota, United States
Minnesota Oncology - Minneapolis Clinic
🇺🇸Minneapolis, Minnesota, United States
UCSF
🇺🇸San Francisco, California, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
SCRI at Healthone
🇺🇸Denver, Colorado, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Memorial Cancer Institute
🇺🇸Pembroke Pines, Florida, United States
Queen Elizabeth Hospital
🇦🇺Woodville South, Australia
Institut de Cancérologie de l'Ouest
🇫🇷Saint-Herblain, France
Severance Hospital - Yonsei Cancer Center
🇰🇷Soeul, Korea, Republic of
Clinica Universidad de Navarra
🇪🇸Madrid, Spain
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Saint Louis Hospital
🇫🇷Paris, France
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Cancer and Blood Specialty Clinic (CBSC)
🇺🇸Los Alamitos, California, United States
USC Norris
🇺🇸Los Angeles, California, United States
UC Irvine Manchester Pavilion
🇺🇸Orange, California, United States
FL Cancer Specialists - Lake Mary
🇺🇸Lake Mary, Florida, United States
Fort Wayne Medical Oncology and Hematology
🇺🇸Fort Wayne, Indiana, United States
UCLA
🇺🇸Los Angeles, California, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Ochsner Cancer
🇺🇸Jefferson, Louisiana, United States
Maryland Oncology Hematology, PA - Columbia
🇺🇸Columbia, Maryland, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
Gabrail Cancer Research
🇺🇸Canton, Ohio, United States
Texas Oncology - Austin
🇺🇸Austin, Texas, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
US Oncology - Dallas
🇺🇸Dallas, Texas, United States
US Oncology- Texas Oncology - Fort Worth
🇺🇸Fort Worth, Texas, United States
The University of Texas, MD Anderson
🇺🇸Houston, Texas, United States
Texas Oncology - San Antonio Northeast
🇺🇸San Antonio, Texas, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
US Oncology- Virginia Oncology - Norfolk
🇺🇸Norfolk, Virginia, United States
Tasman Health
🇦🇺Southport, Australia
Seattle Cancer Alliance - Fred Hutch
🇺🇸Seattle, Washington, United States
Southern Medical Day Care Centre
🇦🇺Wollongong, New South Wales, Australia
Napean Cancer Care
🇦🇺Kingswood, Australia
Westmead
🇦🇺Westmead, New South Wales, Australia
Institut Bergonié
🇫🇷Bordeaux, France
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Gustave Roussy
🇫🇷Villejuif, France
Samsung Medical Center
🇰🇷Seoul, Gangnam-gu, Korea, Republic of
Gachon University Gil Hospital
🇰🇷Gyeonggi-do, Seongnam-si, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Seongnam-si, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Vall d'Hebron Institut d'Oncologia
🇪🇸Barcelona, Spain
Madrid FJD
🇪🇸Madrid, Spain
Madrid CIOCC - HM Universitario Sanchinnarro
🇪🇸Madrid, Spain
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
SCRI - Tennessee
🇺🇸Nashville, Tennessee, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States