Clinical trial NCT04553692: Phase 1a/1b Study of Aplitabart (IGM-8444) Alone or in Combination in Participants with Relapsed, Refractory, or Newly Diagnosed Cancers
Official title: An Open-label, Multicenter, Phase 1a/1b Study of Aplitibart (IGM-8444) As a Single Agent and in Combination in Participants with Relapsed, Refractory, or Newly Diagnosed Cancers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumor
Colorectal Cancer
Non Hodgkin Lymphoma
Sarcoma
Chondrosarcoma
Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia
Acute Myeloid Leukemia
Keywords: Relapsed and/or Refractory
Metastatic Cancer
Advanced Tumors
Hematological cancer
Newly diagnosed
Lead sponsor: IGM Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-17
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: From Cycle 1 Day 1 through 28 days after the final dose of study drug
measure: 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
timeFrame: 4 weeks
measure: Ph1b: Progression-Free Survival (PFS)
timeFrame: Study duration of approximately 36 months
Secondary outcomes:
measure: Ph1a and Ph1b: Area Under the Curve (AUC) of aplitabart
timeFrame: At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
measure: Ph1a and Ph1b: Clearance (CL) of aplitabart
timeFrame: At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
measure: Ph1a and Ph1b: Volume of distribution (V) of aplitabart
timeFrame: At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
measure: Ph1a and Ph1b: Maximum Concentration (c-max) of aplitabart
timeFrame: At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
measure: Ph1a and Ph1b: Immunogenicity
timeFrame: through end of treatment at approximately 6 months
measure: Ph1a and Ph1b: Objective Response Rate (ORR)
timeFrame: Study duration of approximately 36 months
measure: Ph1a and Ph1b: Duration of Response (DoR)
timeFrame: Study duration of approximately 36 months
measure: Ph1a: Progression-Free Survival (PFS)
timeFrame: Study duration of approximately 36 months
measure: Ph1a and Ph1b: Overall Survival (OS)
timeFrame: Study duration of approximately 36 months
measure: Ph1b: Adverse events of aplitabart + FOLFIRI + bevacizumab
timeFrame: From Cycle 1 Day 1 through 28 days after the final dose of study drug
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Alamitos
country: United States
facility: Cancer and Blood Specialty Clinic (CBSC)
state: California
city: Los Angeles
country: United States
facility: USC Norris
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Orange
country: United States
facility: UC Irvine Manchester Pavilion
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Denver
country: United States
facility: SCRI at Healthone
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Lake Mary
country: United States
facility: FL Cancer Specialists - Lake Mary
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Jefferson
country: United States
facility: Ochsner Cancer
state: Louisiana
city: Columbia
country: United States
facility: Maryland Oncology Hematology, PA - Columbia
state: Maryland
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Oncology - Minneapolis Clinic
state: Minnesota
city: Minneapolis
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Canton
country: United States
facility: Gabrail Cancer Research
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Nashville
country: United States
facility: SCRI - Tennessee
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Dallas
country: United States
facility: US Oncology - Dallas
state: Texas
city: Fort Worth
country: United States
facility: US Oncology- Texas Oncology - Fort Worth
state: Texas
city: Houston
country: United States
facility: The University of Texas, MD Anderson
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Northeast
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Norfolk
country: United States
facility: US Oncology- Virginia Oncology - Norfolk
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Alliance - Fred Hutch
state: Washington
city: Westmead
country: Australia
facility: Westmead
state: New South Wales
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Kingswood
country: Australia
facility: Napean Cancer Care
city: Southport
country: Australia
facility: Tasman Health
city: Woodville South
country: Australia
facility: Queen Elizabeth Hospital
city: Bordeaux
country: France
facility: Institut Bergonié
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Paris
country: France
facility: Saint Louis Hospital
city: Saint-Herblain
country: France
facility: Institut de Cancérologie de l'Ouest
city: Villejuif
country: France
facility: Gustave Roussy
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnam-gu
city: Gyeonggi-do
country: Korea, Republic of
facility: Gachon University Gil Hospital
state: Seongnam-si
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Seongnam-si
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Soeul
country: Korea, Republic of
facility: Severance Hospital - Yonsei Cancer Center
city: Barcelona
country: Spain
facility: Vall d'Hebron Institut d'Oncologia
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: Madrid FJD
city: Madrid
country: Spain
facility: Madrid CIOCC - HM Universitario Sanchinnarro
Study officials:
affiliation: IGM Biosciences
name: Eric Humke, MD, PhD
role: STUDY_DIRECTOR
References: