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Trial record 1 of 1 for:    NCT04553692
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Phase 1a/1b Study of Aplitabart (IGM-8444) Alone or in Combination in Participants With Relapsed, Refractory, or Newly Diagnosed Cancers

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ClinicalTrials.gov Identifier: NCT04553692
Recruitment Status : Recruiting
First Posted : September 17, 2020
Last Update Posted : April 16, 2024
Sponsor:
Information provided by (Responsible Party):
IGM Biosciences, Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Solid Tumor Colorectal Cancer Non Hodgkin Lymphoma Sarcoma Chondrosarcoma Small Lymphocytic Lymphoma Chronic Lymphocytic Leukemia Acute Myeloid Leukemia Drug: Aplitabart (IGM-8444) Drug: FOLFIRI Drug: Bevacizumab (and approved biosimilars) Drug: Birinapant Drug: Venetoclax Drug: Gemcitabine Drug: Docetaxel Drug: Azacitidine Phase 1

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 430 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Masking Description: Phase 1a is non-randomized; Ph1b is randomized
Primary Purpose: Treatment
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
Actual Study Start Date : September 23, 2020
Estimated Primary Completion Date : June 2026
Estimated Study Completion Date : August 2027

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Ph1a: Aplitabart Single Agent Alternate Dosing Escalation
Aplitabart will be administered intravenously as a single agent on an alternate dosing schedule.
 Drug: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug
Experimental: Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion
Aplitabart will be administered intravenously in combination with FOLFIRI± bevacizumab.
 Drug: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug

Drug: FOLFIRI
Chemotherapy Regimen
Other Names:
  • Fluorouracil or 5-FU
  • Leucovorin
  • Irinotecan

Drug: Bevacizumab (and approved biosimilars)
Targeted Therapy
Other Name: Avastin
Experimental: Ph1a: Aplitabart + Birinapant Escalation and Expansion
Aplitabart will be administered intravenously in combination with Birinapant which will also be administered intravenously.
 Drug: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug

Drug: Birinapant
SMAC-mimetic Investigational Drug
Experimental: Ph1a: Aplitabart + Venetoclax Escalation and Expansion
Aplitabart will be administered intravenously in combination with Venetoclax.
 Drug: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug

Drug: Venetoclax
Targeted Therapy
Other Name: Venclexta
Experimental: Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion
Aplitabart will be administered intravenously in combination with Docetaxel and Gemcitabine.
 Drug: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug

Drug: Gemcitabine
Chemotherapy
Other Name: Gemzar

Drug: Docetaxel
Chemotherapy
Other Names:
  • Taxotere
  • Docefrez
Experimental: Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion
Aplitabart will be administered intravenously in combination with Venetoclax and Azacitidine.
 Drug: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug

Drug: Venetoclax
Targeted Therapy
Other Name: Venclexta

Drug: Azacitidine
Chemotherapy
Other Name: VIDAZA
Experimental: Ph1b: Aplitabart + FOLFIRI + Bevacizumab
Aplitabart will be administered intravenously in combination with FOLFIRI + bevacizumab
 Drug: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug

Drug: FOLFIRI
Chemotherapy Regimen
Other Names:
  • Fluorouracil or 5-FU
  • Leucovorin
  • Irinotecan

Drug: Bevacizumab (and approved biosimilars)
Targeted Therapy
Other Name: Avastin
Experimental: Ph1b: FOLFIRI + Bevacizumab
Standard of Care FOLFIRI + bevacizumab will be administered intravenously
 Drug: FOLFIRI
Chemotherapy Regimen
Other Names:
  • Fluorouracil or 5-FU
  • Leucovorin
  • Irinotecan

Drug: Bevacizumab (and approved biosimilars)
Targeted Therapy
Other Name: Avastin


Outcome Measures
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Primary Outcome Measures :
  1. 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 [ Time Frame: 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

  2. 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 [ Time Frame: 4 weeks ]
    Relationship between aplitabart dose and safety, PK, activity, and endpoints.

  3. Ph1b: Progression-Free Survival (PFS) [ Time Frame: 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 Outcome Measures :
  1. Ph1a and Ph1b: Area Under the Curve (AUC) of aplitabart [ Time Frame: 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.

  2. Ph1a and Ph1b: Clearance (CL) of aplitabart [ Time Frame: 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.

  3. Ph1a and Ph1b: Volume of distribution (V) of aplitabart [ Time Frame: 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.

  4. Ph1a and Ph1b: Maximum Concentration (c-max) of aplitabart [ Time Frame: 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.

  5. Ph1a and Ph1b: Immunogenicity [ Time Frame: through end of treatment at approximately 6 months ]
    Immunogenicity as assessed by detection of anti-drug antibodies (ADAs) to aplitabart

  6. Ph1a and Ph1b: Objective Response Rate (ORR) [ Time Frame: Study duration of approximately 36 months ]
    Preliminary efficacy of objective response rate (ORR)

  7. Ph1a and Ph1b: Duration of Response (DoR) [ Time Frame: Study duration of approximately 36 months ]
    Preliminary efficacy of duration of response (DoR)

  8. Ph1a: Progression-Free Survival (PFS) [ Time Frame: 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.

  9. Ph1a and Ph1b: Overall Survival (OS) [ Time Frame: 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

  10. Ph1b: Adverse events of aplitabart + FOLFIRI + bevacizumab [ Time Frame: 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04553692


Contacts
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Contact: Clinical Trials (877) 544-6728 clinicaltrials@igmbio.com

Locations
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Sponsors and Collaborators
IGM Biosciences, Inc.
Investigators
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Study Director: Eric Humke, MD, PhD IGM Biosciences
More Information
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Responsible Party: IGM Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT04553692    
Other Study ID Numbers: IGM-8444-001
First Posted: September 17, 2020    Key Record Dates
Last Update Posted: April 16, 2024
Last Verified: April 2024

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by IGM Biosciences, Inc.:
Relapsed and/or Refractory
Metastatic Cancer
Advanced Tumors
Hematological cancer
Newly diagnosed
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Chondrosarcoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hematologic Diseases
Sarcoma
Neoplasms, Connective and Soft Tissue
Leukemia, Lymphoid
Leukemia, B-Cell
 Chronic Disease
Disease Attributes
Pathologic Processes
Neoplasms, Connective Tissue
Leucovorin
Bevacizumab
Gemcitabine
Docetaxel
Fluorouracil
Irinotecan
Azacitidine
Venetoclax
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors