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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04553692




Registration number
NCT04553692
Ethics application status
Date submitted
4/09/2020
Date registered
17/09/2020
Date last updated
16/04/2024

Titles & IDs
Public title
Phase 1a/1b Study of Aplitabart (IGM-8444) Alone or in Combination in Participants With Relapsed, Refractory, or Newly Diagnosed Cancers
Scientific 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
Secondary ID [1] 0 0
IGM-8444-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor 0 0
Colorectal Cancer 0 0
Non Hodgkin Lymphoma 0 0
Sarcoma 0 0
Chondrosarcoma 0 0
Small Lymphocytic Lymphoma 0 0
Chronic Lymphocytic Leukemia 0 0
Acute Myeloid Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Aplitabart (IGM-8444)
Treatment: Drugs - FOLFIRI
Treatment: Drugs - Bevacizumab (and approved biosimilars)
Treatment: Drugs - Birinapant
Treatment: Drugs - Venetoclax
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Docetaxel
Treatment: Drugs - Azacitidine

Experimental: Ph1a: Aplitabart Single Agent Alternate Dosing Escalation - Aplitabart will be administered intravenously as a single agent on an alternate dosing schedule.

Experimental: Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion - Aplitabart will be administered intravenously in combination with FOLFIRI± bevacizumab.

Experimental: Ph1a: Aplitabart + Birinapant Escalation and Expansion - Aplitabart will be administered intravenously in combination with Birinapant which will also be administered intravenously.

Experimental: Ph1a: Aplitabart + Venetoclax Escalation and Expansion - Aplitabart will be administered intravenously in combination with Venetoclax.

Experimental: Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion - Aplitabart will be administered intravenously in combination with Docetaxel and Gemcitabine.

Experimental: Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion - Aplitabart will be administered intravenously in combination with Venetoclax and Azacitidine.

Experimental: Ph1b: Aplitabart + FOLFIRI + Bevacizumab - Aplitabart will be administered intravenously in combination with FOLFIRI + bevacizumab

Experimental: Ph1b: FOLFIRI + Bevacizumab - Standard of Care FOLFIRI + bevacizumab will be administered intravenously


Treatment: Drugs: Aplitabart (IGM-8444)
DR5 Agonist Investigational Drug

Treatment: Drugs: FOLFIRI
Chemotherapy Regimen

Treatment: Drugs: Bevacizumab (and approved biosimilars)
Targeted Therapy

Treatment: Drugs: Birinapant
SMAC-mimetic Investigational Drug

Treatment: Drugs: Venetoclax
Targeted Therapy

Treatment: Drugs: Gemcitabine
Chemotherapy

Treatment: Drugs: Docetaxel
Chemotherapy

Treatment: Drugs: Azacitidine
Chemotherapy
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
From Cycle 1 Day 1 through 28 days after the final dose of study drug
Primary outcome [2] 0 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
Timepoint [2] 0 0
4 weeks
Primary outcome [3] 0 0
Ph1b: Progression-Free Survival (PFS)
Timepoint [3] 0 0
Study duration of approximately 36 months
Secondary outcome [1] 0 0
Ph1a and Ph1b: Area Under the Curve (AUC) of aplitabart
Timepoint [1] 0 0
At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Secondary outcome [2] 0 0
Ph1a and Ph1b: Clearance (CL) of aplitabart
Timepoint [2] 0 0
At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Secondary outcome [3] 0 0
Ph1a and Ph1b: Volume of distribution (V) of aplitabart
Timepoint [3] 0 0
At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Secondary outcome [4] 0 0
Ph1a and Ph1b: Maximum Concentration (c-max) of aplitabart
Timepoint [4] 0 0
At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Secondary outcome [5] 0 0
Ph1a and Ph1b: Immunogenicity
Timepoint [5] 0 0
through end of treatment at approximately 6 months
Secondary outcome [6] 0 0
Ph1a and Ph1b: Objective Response Rate (ORR)
Timepoint [6] 0 0
Study duration of approximately 36 months
Secondary outcome [7] 0 0
Ph1a and Ph1b: Duration of Response (DoR)
Timepoint [7] 0 0
Study duration of approximately 36 months
Secondary outcome [8] 0 0
Ph1a: Progression-Free Survival (PFS)
Timepoint [8] 0 0
Study duration of approximately 36 months
Secondary outcome [9] 0 0
Ph1a and Ph1b: Overall Survival (OS)
Timepoint [9] 0 0
Study duration of approximately 36 months
Secondary outcome [10] 0 0
Ph1b: Adverse events of aplitabart + FOLFIRI + bevacizumab
Timepoint [10] 0 0
From Cycle 1 Day 1 through 28 days after the final dose of study drug

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2027
Actual
Sample size
Target
430
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Westmead - Westmead
Recruitment hospital [2] 0 0
Southern Medical Day Care Centre - Wollongong
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
Napean Cancer Care - Kingswood
Recruitment hospital [5] 0 0
Tasman Health - Southport
Recruitment hospital [6] 0 0
Queen Elizabeth Hospital - Woodville South
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
2500 - Wollongong
Recruitment postcode(s) [3] 0 0
3052 - Melbourne
Recruitment postcode(s) [4] 0 0
2747 - Kingswood
Recruitment postcode(s) [5] 0 0
QLD 4215 - Southport
Recruitment postcode(s) [6] 0 0
5011 - Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oklahoma
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
France
State/province [20] 0 0
Bordeaux
Country [21] 0 0
France
State/province [21] 0 0
Dijon
Country [22] 0 0
France
State/province [22] 0 0
Paris
Country [23] 0 0
France
State/province [23] 0 0
Saint-Herblain
Country [24] 0 0
France
State/province [24] 0 0
Villejuif
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Gangnam-gu
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Seongnam-si
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Seoul
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Soeul
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
IGM Biosciences, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04553692
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Eric Humke, MD, PhD
Address 0 0
IGM Biosciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical Trials
Address 0 0
Country 0 0
Phone 0 0
(877) 544-6728
Fax 0 0
Email 0 0
clinicaltrials@igmbio.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04553692