This phase I trial is trying to determine the dose of two combined oral therapies (ipatasertib and rucaparib) as a treatment for advanced breast, ovarian or prostate cancerA Phase Ib, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Ipatasertib in Combination With Rucaparib in Patients With Advanced Breast, Ovarian, or Prostate Cancer

Inclusion

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• A life expectancy of at least 3 months
• Ability to swallow oral study drug
• Have adequate organ and marrow function as confirmed by the laboratory values listed below, obtained within 28 days prior to the first dose of study treatment:

• Bone marrow function assessments (without transfusion within 28 days prior to receipt of study treatment):

  1. ANC >= 1500 cells/uL (1.5 x 10^9/L) without granulocyte-colony stimulating factor support
  2. Platelet count >= 100.0 x 10^9/L
  3. Hemoglobin >= 9 g/dL (or 5.6 mmol/L)

• Chemistry panel assessments:

  1. AST and ALT <= 1.5 x upper limit of normal (ULN); if liver metastases, <= 2.5 x ULN
  2. Bilirubin <= 1.5 x ULN (<= 3 x ULN if hyperbilirubinemia is due to Gilbert's syndrome)
  3. Serum albumin >= 3.0 g/dL
  4. Serum creatinine <= 1.5 x ULN or creatinine clearance >= 50 mL/min
  5. Fasting glucose <= 150 mg/dL and hemoglobin A1c <= 7.5%
• Resolved or stabilized toxicities resulting from previous therapy to Grade 1 (except for alopecia and neuropathy).

Cancer-Related Inclusion Criteria

• Have a histologically confirmed diagnosis of ovarian (Part 1 only), breast (Part 1 only) or prostate cancer (Part 1 and Part 2)
• Disease must be either metastatic or locally advanced disease that cannot be treated with curative intent

• For patients with ovarian cancer (Part 1 only):

  1. High-grade (2 or 3) serous or endometrioid or clear cell epithelial ovarian, fallopian tube, or primary peritoneal cancer (PPC)
  2. Must have received at least one prior platinum-based therapy and may have platinumsensitive disease (i.e., documented radiologic disease progression >= 6 months following the last dose of the platinum treatment administered) or platinum-resistant disease
  3. Have a CA-125 level that is > 2 x ULN
  4. Must have measurable disease by RECIST v1.1

• For patients with breast cancer (Part 1 only): must be human epidermal growth factor receptor 2 negative (HER2-) (estrogen receptor [ER]/progesterone positive or negative):

  1. ER/progesterone-positive patients must have received and progressed on at least one endocrine therapy (adjuvant or metastatic)
  2. ER/progesterone-negative/HER2- (triple-negative breast cancer [TNBC]) patients must have received at least one prior line of chemotherapy for metastatic breast cancer
  3. Must not have received more than two prior lines of chemotherapy for metastatic breast cancer
  4. Must have measurable disease by RECIST v1.1

For patients with prostate cancer:

1. Adenocarcinoma of the prostate without small cell or neuroendocrine features
2. Surgical or medical castration with testosterone < 50 ng/dL (1.7 nM)
3. Patients treated with luteinizing hormone-releasing hormone analogs must have initiated therapy at least 4 weeks prior to the first dose of study treatment and continue throughout the study treatment
4. Progression of prostate cancer either via PSA progression (two rising PSA levels measured >= 1 week apart, with second result >= 1 ng/mL) or radiographic progression with or without PSA progression
5. Must have received at least one prior line of second-generation androgen receptor targeted therapy (e.g., abiraterone, enzalutamide, apalutamide)

6. Patients with prostate cancer must have either measurable disease by RECIST v1.1 or bone lesions by bone scan, or both.

   • Submission of a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or a minimum of 12 freshly cut, unstained, serial tumor slides from the most recently collected tumor tissue for central molecular analysis (retrospective NGS testing for HR and PI3K-AKT pathway status and for other protocol-mandated secondary and exploratory assessments). Cytologic or fine needle aspirate samples are not acceptable. Tumor tissue from bone metastases is not acceptable.
   • For men and women of child bearing potential: agreement to remain abstinent or use protocol defined contraceptive measures during the treatment period and for at least 28 days after the last dose of ipatasertib,or 6 months after the last dose of rucaparib, whichever occurs later