A Study to Evaluate Safety/Tolerability of Immunotherapy Combinations in Participants With Triple-Negative Breast Cancer or Gynecologic Malignancies

Ovarian Cancer Clinical Trial

Official title:

A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Breast or Gynecologic Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03719326
• Other study ID #: ARC-2 (AB928CSP0002)
• Status: Completed
• Phase: Phase 1
• Start date: October 15, 2018
• Est. completion date: July 2, 2021

Study information

• Verified date: May 2024
• Source: Arcus Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

In the dose escalation phase, the following will be assessed:

• Arm A: escalating doses of etrumadenant in combination with PLD at standard doses will be assessed in participants with advanced metastatic triple-negative breast cancer or ovarian cancer. Eligible participants will receive oral administration of etrumadenant as well as intravenous (IV) infusion of PLD. The recommended dose (RDE) for expansion Arms 1 and 2 and escalation Arm C will be determined upon completion of this dose escalation arm.

• Arm B: escalating doses of etrumadenant in combination with the NP at standard doses will also be assessed in participants with advanced metastatic TNBC. Eligible participants will receive oral administration of etrumadenant as well as NP infusion. The RDE of etrumadenant will be determined upon completion of this dose escalation arm.

• Arm C: escalating doses of IPI-549 in combination with the RDE of etrumadenant (from Arm A) and PLD at standard doses will be assessed in participants with advanced metastatic TNBC or ovarian cancer. Eligible participants will receive oral administration of both etrumadenant and IPI-549 as well as IV infusion of PLD. The RDE of IPI-549 for expansion Arm 4 will be determined upon completion of this dose escalation arm.

In the dose expansion phase, the following will be assessed:

• Arms 1 and 2: Etrumadenant at the RDE in combination with PLD at standard doses may be assessed in participants with advanced metastatic TNBC or ovarian cancer.

• Arm 3: Etrumadenant at the RDE in combination with NP at standard doses may be assessed in participants with advanced metastatic TNBC.

• Arm 4: Etrumadenant and IPI-549 at the RDE in combination with PLD at standard doses may be assessed in participants with advanced metastatic TNBC.

Overall duration of treatment will depend on how well the treatment is tolerated. Treatment may continue until unacceptable toxicity or progressive disease or other reasons specified in the protocol.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: July 2, 2021
• Est. primary completion date: July 1, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

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)

Related Conditions & MeSH terms

• Breast Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• TNBC - Triple-Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist for oral use
• IPI-549
IPI-549 is a phosphoinositide-3-kinase-gamma inhibitor for oral use
• Pegylated liposomal doxorubicin (PLD)
Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use
• nanoparticle albumin-bound paclitaxel (NP)
NP is a microtubule inhibitor for intravenous (IV) use

Locations

Country	Name	City	State
Australia	Pindara Private Hospital	Benowa	Queensland
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	The Kinghorn Cancer Centre	Darlinghurst	New South Wales
Australia	Peninsula & South Eastern Haematology and Oncology Group	Frankston	Victoria
Australia	St. George Private Hospital	Kogarah	New South Wales
Australia	Macquarie University	Macquarie	New South Wales
Australia	Cabrini Hospital	Malvern	Victoria
United States	Rocky Mountain Cancer Centers (Aurora)	Aurora	Colorado
United States	Texas Oncology, P.A. - Austin (Midtown)	Austin	Texas
United States	Texas Oncology, P.A. - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Texas Oncology, P.A. - Fort Worth Cancer Center	Fort Worth	Texas
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	University of California, Los Angeles	Los Angeles	California
United States	Miami Cancer Institute at Baptist Health	Miami	Florida
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Maryland Oncology Hematology, PA	Rockville	Maryland
United States	HealthPartners Institute Cancer Care Center	Saint Paul	Minnesota
United States	Texas Oncology, P.A. - San Antonio Medical Center	San Antonio	Texas
United States	Texas Oncology, P.A. - San Antonio Northeast	San Antonio	Texas
United States	Scottsdale Healthcare Hospitals dba Honor Health Research Institute	Scottsdale	Arizona
United States	Medical Oncology Associates dba Summit Cancer Centers	Spokane	Washington
United States	MultiCare Regional Cancer Center	Tacoma	Washington
United States	Arizona Clinical Research Center	Tucson	Arizona
United States	Texas Oncology, P.A. - Tyler	Tyler	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Arcus Biosciences, Inc.	Infinity Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events (AEs)		From first dose date to 30 days after the last dose (Approximately 1 year)
Primary	Incidence of dose-limiting toxicities (DLTs) during the dose escalation phase		From first dose date to 28 days after the first dose
Secondary	Plasma concentration of etrumadenant		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	Plasma concentration of IPI-549		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	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		From study enrollment until participation discontinuation, first occurrence of progressive disease or death from any cause, whichever occurs first (approximately 3-5 years)
Secondary	Percentage of participants with Disease Control (complete response, partial response, or stable disease) for > 6 months as determined by RECIST v1.1		From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years)
Secondary	Duration of Response as determined by the Investigator according to RECIST v1.1		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	Progression Free Survival (PFS) as determined by the Investigator according to RECIST v1.1		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	Overall Survival (OS) as determined by the Investigator according to RECIST v1.1		From start of treatment up to death from any cause (up to approximately 3-5 years)
Secondary	Percentage of etrumadenant target inhibition in peripheral blood		Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and at the end of treatment (in total approximately 5 months)
Secondary	Immunophenotyping activity in select immune subsets for etrumadenant and IPI-549 in peripheral blood		Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and at the end of treatment (in total approximately 5 months).

External Links

•   ARC-2 - Lay Summary (English Version)