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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04553692
• Other study ID #: IGM-8444-001
• Status: Recruiting
• Phase: Phase 1
• Start date: September 23, 2020
• Est. completion date: August 2027

Study information

• Verified date: April 2024
• Source: IGM Biosciences, Inc.
• Contact: Clinical Trials
• Phone: (877) 544-6728
• Email: clinicaltrials[@]igmbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 430
• Est. completion date: August 2027
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Chondrosarcoma
• Chronic Lymphocytic Leukemia
• Colorectal Cancer
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Non Hodgkin Lymphoma
• Sarcoma
• Small Lymphocytic Lymphoma
• Solid Tumor

Intervention

Drug:
• Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug
• FOLFIRI
Chemotherapy Regimen
• Bevacizumab (and approved biosimilars)
Targeted Therapy
• Birinapant
SMAC-mimetic Investigational Drug
• Venetoclax
Targeted Therapy
• Gemcitabine
Chemotherapy
• Docetaxel
Chemotherapy
• Azacitidine
Chemotherapy

Locations

Country	Name	City	State
Australia	Napean Cancer Care	Kingswood
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Tasman Health	Southport
Australia	Westmead	Westmead	New South Wales
Australia	Southern Medical Day Care Centre	Wollongong	New South Wales
Australia	Queen Elizabeth Hospital	Woodville South
France	Institut Bergonié	Bordeaux
France	Centre Georges Francois Leclerc	Dijon
France	Saint Louis Hospital	Paris
France	Institut de Cancérologie de l'Ouest	Saint-Herblain
France	Gustave Roussy	Villejuif
Korea, Republic of	Gachon University Gil Hospital	Gyeonggi-do	Seongnam-si
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul	Gangnam-gu
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital - Yonsei Cancer Center	Soeul
Spain	Vall d'Hebron Institut d'Oncologia	Barcelona
Spain	Clinica Universidad de Navarra	Madrid
Spain	Madrid CIOCC - HM Universitario Sanchinnarro	Madrid
Spain	Madrid FJD	Madrid
United States	Texas Oncology - Austin	Austin	Texas
United States	Gabrail Cancer Research	Canton	Ohio
United States	Maryland Oncology Hematology, PA - Columbia	Columbia	Maryland
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	US Oncology - Dallas	Dallas	Texas
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	SCRI at Healthone	Denver	Colorado
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	US Oncology- Texas Oncology - Fort Worth	Fort Worth	Texas
United States	START Midwest	Grand Rapids	Michigan
United States	The University of Texas, MD Anderson	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	Ochsner Cancer	Jefferson	Louisiana
United States	FL Cancer Specialists - Lake Mary	Lake Mary	Florida
United States	Cancer and Blood Specialty Clinic (CBSC)	Los Alamitos	California
United States	UCLA	Los Angeles	California
United States	USC Norris	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Mayo Clinic	Minneapolis	Minnesota
United States	Minnesota Oncology - Minneapolis Clinic	Minneapolis	Minnesota
United States	SCRI - Tennessee	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	US Oncology- Virginia Oncology - Norfolk	Norfolk	Virginia
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	UC Irvine Manchester Pavilion	Orange	California
United States	Memorial Cancer Institute	Pembroke Pines	Florida
United States	Mayo Clinic	Phoenix	Arizona
United States	Providence Portland Medical Center	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Texas Oncology - San Antonio Northeast	San Antonio	Texas
United States	UCSF	San Francisco	California
United States	Florida Cancer Specialists	Sarasota	Florida
United States	Seattle Cancer Alliance - Fred Hutch	Seattle	Washington
United States	Texas Oncology - Tyler	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
IGM Biosciences, Inc.

Countries where clinical trial is conducted

United States,  Australia,  France,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	From Cycle 1 Day 1 through 28 days after the final dose of study drug
Primary	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.	4 weeks
Primary	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.	Study duration of approximately 36 months
Secondary	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.	At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Secondary	Ph1a and Ph1b: Clearance (CL) of aplitabart	Clearance (CL) of aplitabart as a single agent and in combination with the anticancer agents listed above.	At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Secondary	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.	At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Secondary	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.	At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Secondary	Ph1a and Ph1b: Immunogenicity	Immunogenicity as assessed by detection of anti-drug antibodies (ADAs) to aplitabart	through end of treatment at approximately 6 months
Secondary	Ph1a and Ph1b: Objective Response Rate (ORR)	Preliminary efficacy of objective response rate (ORR)	Study duration of approximately 36 months
Secondary	Ph1a and Ph1b: Duration of Response (DoR)	Preliminary efficacy of duration of response (DoR)	Study duration of approximately 36 months
Secondary	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.	Study duration of approximately 36 months
Secondary	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	Study duration of approximately 36 months
Secondary	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	From Cycle 1 Day 1 through 28 days after the final dose of study drug