Phase 1a/1b Study of Aplitabart (IGM-8444) Alone or in Combination in Participants with Relapsed, Refractory, or Newly Diagnosed Cancers

Phase 1TerminatedNCT04553692

IGM Biosciences, Inc.272 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

272

Conditions

Solid Tumor Colorectal Cancer

Interventions

Aplitabart (IGM-8444)DRUG

DR5 Agonist Investigational Drug

FOLFIRIDRUG

Chemotherapy Regimen

Bevacizumab (and approved biosimilars)DRUG

Targeted Therapy

BirinapantDRUG

SMAC-mimetic Investigational Drug

VenetoclaxDRUG

Targeted Therapy

GemcitabineDRUG

Chemotherapy

DocetaxelDRUG

Chemotherapy

AzacitidineDRUG

Chemotherapy

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (58)

Mayo Clinic

Phoenix, Arizona, United States

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

UCLA

Los Angeles, California, United States

Outcomes

Primary Outcomes

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

Incidence of treatment-related AEs graded according to the NCI Common Technology Criteria for Adverse Events (CTCAE) v5.0

Time frame: From Cycle 1 Day 1 through 28 days after the final dose of study drug

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

Relationship between aplitabart dose and safety, PK, activity, and endpoints.

Time frame: 4 weeks

Ph1b: Progression-Free Survival (PFS)

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.

Time frame: Study duration of approximately 36 months

Secondary Outcomes

Ph1a and Ph1b: Area Under the Curve (AUC) of aplitabart

Area Under the Curve (AUC) of aplitabart as a single agent and in combination with the anticancer agents listed above.

Time frame: At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months

Ph1a and Ph1b: Clearance (CL) of aplitabart

Clearance (CL) of aplitabart as a single agent and in combination with the anticancer agents listed above.

Time frame: At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months

Ph1a and Ph1b: Volume of distribution (V) of aplitabart

Volume of distribution (V) of aplitabart as a single agent and in combination with the anticancer agents listed above.

Time frame: At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months

Ph1a and Ph1b: Maximum Concentration (c-max) of aplitabart

Maximum Concentration of aplitabart as a single agent and in combination with the anticancer agents listed above.

Time frame: At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months

Ph1a and Ph1b: Immunogenicity

Immunogenicity as assessed by detection of anti-drug antibodies (ADAs) to aplitabart

Time frame: through end of treatment at approximately 6 months

Ph1a and Ph1b: Objective Response Rate (ORR)

Preliminary efficacy of objective response rate (ORR)

Time frame: Study duration of approximately 36 months

Ph1a and Ph1b: Duration of Response (DoR)

Preliminary efficacy of duration of response (DoR)

Time frame: Study duration of approximately 36 months

Ph1a: Progression-Free Survival (PFS)

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.

Time frame: Study duration of approximately 36 months

Ph1a and Ph1b: Overall Survival (OS)

OS is defined as the time from first dose (Ph1a) or randomization (Ph1b) to death due to any cause

Time frame: Study duration of approximately 36 months

Ph1b: Adverse events of aplitabart + FOLFIRI + bevacizumab

Incidence of treatment-related AEs graded according to the NCI Common Technology Criteria for Adverse Events (CTCAE) v5.0

Time frame: From Cycle 1 Day 1 through 28 days after the final dose of study drug