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

Status: Active

Description

This is a Phase 1 / 1b, open-label, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic, and clinical activity of AB928 in combination with pegylated liposomal doxorubicin (PLD) with or without IPI-549, or AB928 in combination with nanoparticle albumin-bound-paclitaxel (NP) in participants with advanced metastatic triple-negative breast cancer or ovarian cancer.

Eligibility Criteria

Inclusion Criteria

  • Inclusion: 1. Female participants ≥ 18 years of age at the time of screening; 2. Must have at least 1 measurable lesion per RECIST v1.1; 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 4. Confirm that an archival tissue sample is available and ≤ 6 months old; if not, a new biopsy of a tumor lesion must be obtained, or fresh biopsy at screening; 5. Adequate organ and marrow function; 6. Breast Cancer: Participants must have histologically confirmed ER-negative, PgR-negative, and HER2-negative breast cancer (per ASCO/CAP guidelines) that is metastatic, advanced or recurrent with progression for which no alternative or curative therapy exists; OR Ovarian Cancer:Participants must have histologically confirmed ovarian cancer (per ASCO/CAP guidelines) that is metastatic, advanced or recurrent with progression for which no alternative or curative therapy exists; Exclusion: 1. Use of any live vaccines against infectious diseases within 4 weeks (28 days) of initiation of investigational product. 2. Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of investigational product hazardous 3. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 4. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 30 days after the last dose of investigational product administration. 5. QTcF >480 ms with the exception for participants with riht or left bundle branch block. 6. Prior surgery or GI dysfunction that may affect drug absorption for participants assigned to the IPI-549 arm(s). 7. History of peptic ulcer and/or GI bleed within the past 6 months prior to screening for participants assigned to the IPI-549 arm(s). 8. Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in past 2 years 9. Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, breast, or prostate cancer. 10. Prior chemotherapy, targeted small-molecule therapy, or radiation therapy within 4 weeks prior to Day 1 or has not recovered (ie, ≥ Grade 1 or baseline) from AEs due to a previously administered agent 11. Participants who are eligible for potentially curative available therapies or interventions. 12. Use of other investigational drugs within 28 days of investigational product administration 13. For participants who will be dosed with IPI-549, administration of any of the following within 1 week prior to the administration of investigational product: 1. Strong inhibitors or inducers of cytochrome P450 (CYP)3A4, including grapefruit, grapefruit juice, and herbal supplements 2. P-glycoprotein (P-gp) inhibitors and inducers 3. Warfarin, phenytoin, or other substrates of CYP2C8 or CYP2C9 with a narrow therapeutic range 4. Medications associated with QTc interval prolongation or Torsades de Pointes

Locations & Contacts

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: In review
Contact: Nabilah Abdehlaal
Phone: 310-794-6918
Email: nabdelaal@mednet.ucla.edu

Trial Objectives and Outline

Dose escalation of the following will be assessed: - escalating doses of AB928 in combination with pegylated liposomal doxorubicin (PLD) at standard doses in participants with advanced metastatic triple-negative breast cancer or ovarian cancer; - escalating doses of IPI-549 in combination with the recommended phase 2 dose (RP2D) of AB928 and PLD in participants with advanced metastatic triple-negative breast cancer or ovarian cancer; - escalating doses of AB928 in combination with the nanoparticle albumin-bound-paclitaxel (NP) will also be assessed in participants with advanced metastatic triple-negative breast cancer. Dose expansion of the following will be assessed: - AB928 in combination with PLD at standard doses will be assessed in participants with advanced metastatic triple-negative breast cancer or ovarian cancer. The dose of AB928 used will be determined based on the findings from the dose-escalation phase. - AB928 and IPI-549 in combination with PLD at standard doses will be assessed in participants with advanced metastatic triple-negative breast cancer. The dose of AB928 and IPI-549 used will be determined based on the findings from the dose-escalation phase. - AB928 in combination with NP at standard doses will be assessed in participants with advanced metastatic triple-negative breast cancer. The dose of AB928 and NP used will be determined based on the findings from the dose-escalation phase. AB928 and IPI-549 are administered orally, and PLD and NP are both administered via iv infusion. 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.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Arcus Biosciences, Inc.

Trial IDs

Primary ID AB928CSP0002
Secondary IDs NCI-2019-02494
Clinicaltrials.gov ID NCT03719326