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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/NCT03719326




Registration number
NCT03719326
Ethics application status
Date submitted
15/10/2018
Date registered
25/10/2018
Date last updated
24/05/2024

Titles & IDs
Public title
A Study to Evaluate Safety/Tolerability of Immunotherapy Combinations in Participants With Triple-Negative Breast Cancer or Gynecologic Malignancies
Scientific title
A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Breast or Gynecologic Malignancies
Secondary ID [1] 0 0
ARC-2 (AB928CSP0002)
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
TNBC - Triple-Negative Breast Cancer 0 0
Ovarian Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Etrumadenant
Treatment: Drugs - IPI-549
Treatment: Drugs - Pegylated liposomal doxorubicin (PLD)
Treatment: Drugs - nanoparticle albumin-bound paclitaxel (NP)

Experimental: Dose Escalation-Arm A - Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.

Experimental: Dose Escalation-Arm B - Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.

Experimental: Dose Escalation-Arm C - Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.

Experimental: Dose Expansion-TNBC-Arm 1 - The dose given will be determined from the dose escalation part (Arm A).

Experimental: Dose Expansion-Ovarian Cancer-Arm 2 - The dose given will be determined from the dose escalation part (Arm A).

Experimental: Dose Expansion-TNBC-Arm 3 - The dose given will be determined from the dose escalation part (Arm B). .

Experimental: Dose Expansion-TNBC-Arm 4 - The dose expansion will be determined from the dose escalation part (Arm C).


Treatment: Drugs: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist for oral use

Treatment: Drugs: IPI-549
IPI-549 is a phosphoinositide-3-kinase-gamma inhibitor for oral use

Treatment: Drugs: Pegylated liposomal doxorubicin (PLD)
Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use

Treatment: Drugs: nanoparticle albumin-bound paclitaxel (NP)
NP is a microtubule inhibitor for intravenous (IV) use
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Adverse Events (AEs)
Timepoint [1] 0 0
From first dose date to 30 days after the last dose (Approximately 1 year)
Primary outcome [2] 0 0
Incidence of dose-limiting toxicities (DLTs) during the dose escalation phase
Timepoint [2] 0 0
From first dose date to 28 days after the first dose
Secondary outcome [1] 0 0
Plasma concentration of etrumadenant
Timepoint [1] 0 0
Recorded at baseline (prior to first dose), during the first 4 cycles of treatment (4 months) and at the end of treatment (i.e. in total approximately 5 months)
Secondary outcome [2] 0 0
Plasma concentration of IPI-549
Timepoint [2] 0 0
Recorded at baseline (prior to first dose), during the first 4 cycles of treatment (4 months) and at the end of treatment (i.e. in total approximately 5 months)
Secondary outcome [3] 0 0
Percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR), as determined by Investigator according to Response Evaluation in Solid Tumors (RECIST) v 1.1
Timepoint [3] 0 0
From study enrollment until participation discontinuation, first occurrence of progressive disease or death from any cause, whichever occurs first (approximately 3-5 years)
Secondary outcome [4] 0 0
Percentage of participants with Disease Control (complete response, partial response, or stable disease) for > 6 months as determined by RECIST v1.1
Timepoint [4] 0 0
From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years)
Secondary outcome [5] 0 0
Duration of Response as determined by the Investigator according to RECIST v1.1
Timepoint [5] 0 0
From the date of the first occurrence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years)
Secondary outcome [6] 0 0
Progression Free Survival (PFS) as determined by the Investigator according to RECIST v1.1
Timepoint [6] 0 0
From start of the treatment up to first occurrence of progressive disease or death from any cause, whichever occurs first (up to approximately 3-5 years)
Secondary outcome [7] 0 0
Overall Survival (OS) as determined by the Investigator according to RECIST v1.1
Timepoint [7] 0 0
From start of treatment up to death from any cause (up to approximately 3-5 years)
Secondary outcome [8] 0 0
Percentage of etrumadenant target inhibition in peripheral blood
Timepoint [8] 0 0
Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and at the end of treatment (in total approximately 5 months)
Secondary outcome [9] 0 0
Immunophenotyping activity in select immune subsets for etrumadenant and IPI-549 in peripheral blood
Timepoint [9] 0 0
Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and at the end of treatment (in total approximately 5 months).

Eligibility
Key inclusion criteria
- Female participants, 18 years or older

- Measurable disease per radiographic evaluation

- Performance status 0 or 1

- Available archival tissue sample (within 2 years) or a fresh tumor biopsy may be
required

- Adequate organ, cardiac, and bone marrow function

- Dose escalation

- Participants with breast cancer:

- Locally advanced or metastatic triple negative breast cancer (ER-negative,
PgR-negative, and HER2-negative according to ASCO/CAP guidelines) with
disease progression

- No available alternative or curative therapy

- Participants may have received any number of prior therapies for
advanced/recurrent and progressive disease

- Participants with ovarian cancer:

- Locally advanced or metastatic ovarian cancer with disease progression

- No available alternative or curative therapy

- Participants may have received any number of prior therapies for
advanced/recurrent and progressive disease

- Dose expansion

- Participants with breast cancer:

- Locally advanced or metastatic triple negative breast cancer (ER-negative,
PgR-negative, and HER2-negative according to ASCO/CAP guidelines)

- Disease progression after no more than 3 prior lines of therapy

- Participants with ovarian cancer:

- Locally advanced or metastatic ovarian cancer that is platinum-resistant

- Disease progression after no more than 3 prior lines of therapy
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Received a live, attenuated vaccine within 4 weeks prior to first study treatment

- Prior anticancer treatment including approved agents, systemic radiotherapy, or
investigational therapy within 4 weeks prior first study treatment

- Cancer other than the disease under study within 2 years prior to study entry, except
for some cancers with a low risk of spreading like non-melanoma skin cancers

- Inability to swallow oral medications

- Participant is breastfeeding, pregnant, or expects to become pregnant during the study

- Active autoimmune disease or documented history of autoimmune disease within 2 years
prior to first study treatment

- History of peptic ulcer or stomach bleeding within 6 months prior to first study
treatment

- Use of drugs contraindicated by the protocol within 4 weeks prior to and during study
treatment

- Prior treatment with drugs that suppress the immune system within 2 weeks prior to
first study treatment

- Presence of metastases in the brain or cancer spreading into the cerebrospinal fluid -
CSF (leptomeningeal disease)

- HIV, Hepatitis B, and C test results negative prior to first study treatment

- Major surgery within 4 weeks prior to first study treatment

- Participants who have previously received maximum cumulative lifetime anthracycline
dosage or baseline ejection fraction <50% (on heart echography)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/10/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/07/2021
Sample size
Target
Accrual to date
Final
35
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
The Kinghorn Cancer Centre - Darlinghurst
Recruitment hospital [3] 0 0
St. George Private Hospital - Kogarah
Recruitment hospital [4] 0 0
Macquarie University - Macquarie
Recruitment hospital [5] 0 0
Pindara Private Hospital - Benowa
Recruitment hospital [6] 0 0
Peninsula & South Eastern Haematology and Oncology Group - Frankston
Recruitment hospital [7] 0 0
Cabrini Hospital - Malvern
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2109 - Macquarie
Recruitment postcode(s) [5] 0 0
4217 - Benowa
Recruitment postcode(s) [6] 0 0
3199 - Frankston
Recruitment postcode(s) [7] 0 0
3144 - Malvern
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
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Nevada
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Oregon
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Arcus Biosciences, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Infinity Pharmaceuticals, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1/1b, open-label, dose-escalation, and dose-expansion study to evaluate the
safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical activity of
etrumadenant (AB928) in combination with pegylated liposomal doxorubicin (PLD) with or
without IPI-549 in participants with advanced metastatic triple-negative breast cancer (TNBC)
or ovarian cancer, and etrumadenant in combination with nanoparticle albumin-bound-paclitaxel
(NP) in participants with advanced metastatic TNBC.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03719326
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Arcus Biosciences, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03719326