A Study to Evaluate Safety/Tolerability of Immunotherapy Combinations in Participants With Triple-Negative Breast Cancer or Gynecologic Malignancies
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| ClinicalTrials.gov Identifier: NCT03719326 |
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Recruitment Status :
Completed
First Posted : October 25, 2018
Last Update Posted : December 27, 2022
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Sponsor:
Arcus Biosciences, Inc.
Collaborator:
Infinity Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Arcus Biosciences, Inc.
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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 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 35 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | 3+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 : | October 15, 2018 |
| Actual Primary Completion Date : | July 1, 2021 |
| Actual Study Completion Date : | July 2, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Ovarian Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose Escalation-Arm A
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
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Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist for oral use
Other Name: AB928 Drug: Pegylated liposomal doxorubicin (PLD) Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use |
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Experimental: Dose Escalation-Arm B
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
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Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist for oral use
Other Name: AB928 Drug: nanoparticle albumin-bound paclitaxel (NP) NP is a microtubule inhibitor for intravenous (IV) use |
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Experimental: Dose Escalation-Arm C
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
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Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist for oral use
Other Name: 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 |
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Experimental: Dose Expansion-TNBC-Arm 1
The dose given will be determined from the dose escalation part (Arm A).
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Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist for oral use
Other Name: AB928 Drug: Pegylated liposomal doxorubicin (PLD) Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use |
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Experimental: Dose Expansion-Ovarian Cancer-Arm 2
The dose given will be determined from the dose escalation part (Arm A).
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Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist for oral use
Other Name: 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 Name: 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 Name: 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 |
Primary Outcome Measures :
- Incidence of Adverse Events (AEs) [ Time Frame: 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 [ Time Frame: From first dose date to 28 days after the first dose ]
Secondary Outcome Measures :
- Plasma concentration of etrumadenant [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From start of treatment up to death from any cause (up to approximately 3-5 years) ]
- Percentage of etrumadenant target inhibition in peripheral blood [ Time Frame: 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 [ Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and at the end of treatment (in total approximately 5 months). ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
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
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Dose escalation
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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
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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
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Dose expansion
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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
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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
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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)
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): NCT03719326
Locations
Show 27 study locations
Sponsors and Collaborators
Arcus Biosciences, Inc.
Infinity Pharmaceuticals, Inc.
Investigators
| Study Director: | Medical Director | Arcus Biosciences, Inc. |
Additional Information:
| Responsible Party: | Arcus Biosciences, Inc. |
| ClinicalTrials.gov Identifier: | NCT03719326 |
| Other Study ID Numbers: |
ARC-2 (AB928CSP0002) |
| First Posted: | October 25, 2018 Key Record Dates |
| Last Update Posted: | December 27, 2022 |
| Last Verified: | December 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan [SAP], Clinical Study Report [CSR]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Arcus Biosciences, Inc.:
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Triple Negative Breast Cancer TNBC Ovarian Cancer |
Additional relevant MeSH terms:
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Breast Neoplasms Ovarian Neoplasms Triple Negative Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Endocrine Gland Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Genital Neoplasms, Female |
Urogenital Neoplasms Genital Diseases Endocrine System Diseases Gonadal Disorders Paclitaxel Doxorubicin Liposomal doxorubicin Albumin-Bound Paclitaxel Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antibiotics, Antineoplastic |