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

Sponsor

Arcus Biosciences, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03719326

Collaborator

Infinity Pharmaceuticals, Inc. (Industry)

Enrollment

Locations

Arms

32.6

Actual Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
TNBC - Triple-Negative Breast Cancer Ovarian Cancer	Drug: Etrumadenant Drug: IPI-549 Drug: Pegylated liposomal doxorubicin (PLD) Drug: nanoparticle albumin-bound paclitaxel (NP)	Phase 1

Detailed 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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

35 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

3+3 dose escalation3+3 dose escalation

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 15, 2018

Actual Primary Completion Date :

Jul 1, 2021

Actual Study Completion Date :

Jul 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation-Arm A Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.	Drug: Etrumadenant Etrumadenant is an A2aR and A2bR antagonist for oral use Other Names: AB928 Drug: Pegylated liposomal doxorubicin (PLD) Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use
Experimental: Dose Escalation-Arm B Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.	Drug: Etrumadenant Etrumadenant is an A2aR and A2bR antagonist for oral use Other Names: AB928 Drug: nanoparticle albumin-bound paclitaxel (NP) NP is a microtubule inhibitor for intravenous (IV) use
Experimental: Dose Escalation-Arm C Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.	Drug: Etrumadenant Etrumadenant is an A2aR and A2bR antagonist for oral use Other Names: AB928 Drug: IPI-549 IPI-549 is a phosphoinositide-3-kinase-gamma inhibitor for oral use Drug: Pegylated liposomal doxorubicin (PLD) Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use
Experimental: Dose Expansion-TNBC-Arm 1 The dose given will be determined from the dose escalation part (Arm A).	Drug: Etrumadenant Etrumadenant is an A2aR and A2bR antagonist for oral use Other Names: AB928 Drug: Pegylated liposomal doxorubicin (PLD) Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use
Experimental: Dose Expansion-Ovarian Cancer-Arm 2 The dose given will be determined from the dose escalation part (Arm A).	Drug: Etrumadenant Etrumadenant is an A2aR and A2bR antagonist for oral use Other Names: AB928 Drug: Pegylated liposomal doxorubicin (PLD) Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use
Experimental: Dose Expansion-TNBC-Arm 3 The dose given will be determined from the dose escalation part (Arm B). .	Drug: Etrumadenant Etrumadenant is an A2aR and A2bR antagonist for oral use Other Names: AB928 Drug: nanoparticle albumin-bound paclitaxel (NP) NP is a microtubule inhibitor for intravenous (IV) use
Experimental: Dose Expansion-TNBC-Arm 4 The dose expansion will be determined from the dose escalation part (Arm C).	Drug: Etrumadenant Etrumadenant is an A2aR and A2bR antagonist for oral use Other Names: AB928 Drug: IPI-549 IPI-549 is a phosphoinositide-3-kinase-gamma inhibitor for oral use Drug: Pegylated liposomal doxorubicin (PLD) Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use

Outcome Measures

Primary Outcome Measures

Incidence of Adverse Events (AEs) [From first dose date to 30 days after the last dose (Approximately 1 year)]
Incidence of dose-limiting toxicities (DLTs) during the dose escalation phase [From first dose date to 28 days after the first dose]

Secondary Outcome Measures

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)]
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)]
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)]
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)]
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)]
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)]
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)]
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)]
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).]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Scottsdale Healthcare Hospitals dba Honor Health Research Institute	Scottsdale	Arizona	United States	85258
2	Arizona Clinical Research Center	Tucson	Arizona	United States	85715
3	University of California, Los Angeles	Los Angeles	California	United States	90095
4	Rocky Mountain Cancer Centers (Aurora)	Aurora	Colorado	United States	80012
5	Miami Cancer Institute at Baptist Health	Miami	Florida	United States	33176
6	Maryland Oncology Hematology, PA	Rockville	Maryland	United States	20850
7	HealthPartners Institute Cancer Care Center	Saint Paul	Minnesota	United States	55101
8	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
9	Carolina BioOncology Institute	Huntersville	North Carolina	United States	28078
10	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon	United States	97401
11	Texas Oncology, P.A. - Austin (Midtown)	Austin	Texas	United States	78705
12	Texas Oncology, P.A. - Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
13	Texas Oncology, P.A. - Fort Worth Cancer Center	Fort Worth	Texas	United States	76104
14	Texas Oncology, P.A. - San Antonio Northeast	San Antonio	Texas	United States	78217
15	Texas Oncology, P.A. - San Antonio Medical Center	San Antonio	Texas	United States	78240
16	Texas Oncology, P.A. - Tyler	Tyler	Texas	United States	75702
17	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
18	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
19	Medical Oncology Associates dba Summit Cancer Centers	Spokane	Washington	United States	99216
20	MultiCare Regional Cancer Center	Tacoma	Washington	United States	98405
21	Chris O'Brien Lifehouse	Camperdown	New South Wales	Australia	2050
22	The Kinghorn Cancer Centre	Darlinghurst	New South Wales	Australia	2010
23	St. George Private Hospital	Kogarah	New South Wales	Australia	2217
24	Macquarie University	Macquarie	New South Wales	Australia	2109
25	Pindara Private Hospital	Benowa	Queensland	Australia	4217
26	Peninsula & South Eastern Haematology and Oncology Group	Frankston	Victoria	Australia	3199
27	Cabrini Hospital	Malvern	Victoria	Australia	3144