Solid Tumor, Colorectal Cancer, Non Hodgkin Lymphoma, Sarcoma, Chondrosarcoma, Small Lymphocytic Lymphoma, Chronic Lymphocytic Leukemia, Acute Myeloid Leukemia
Conditions
Keywords
Relapsed and/or Refractory, Metastatic Cancer, Advanced Tumors, Hematological cancer, Newly diagnosed
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.
Interventions
DRUGAplitabart (IGM-8444)
DR5 Agonist Investigational Drug
DRUGFOLFIRI
Chemotherapy Regimen
DRUGBevacizumab (and approved biosimilars)
Targeted Therapy
DRUGBirinapant
SMAC-mimetic Investigational Drug
DRUGVenetoclax
Targeted Therapy
DRUGGemcitabine
Chemotherapy
DRUGDocetaxel
Chemotherapy
DRUGAzacitidine
Chemotherapy
Sponsors
IGM Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Phase 1a is non-randomized; Ph1b is randomized
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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: 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 |
| 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: Objective Response Rate (ORR) | Study duration of approximately 36 months | Preliminary efficacy of objective response rate (ORR) |
| 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: 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. |
Countries
Australia, France, South Korea, Spain, United States
Outcome results
None listed