NUV-868 as Monotherapy and in Combination With Olaparib or Enzalutamide in Adult Patients With Advanced Solid Tumors

Prior treatment

• Have received chemotherapy, hormonal therapy (except for ongoing luteinizing hormone-releasing hormone [LHRH] analogs in male patients and premenopausal women), radiation, or biological anticancer therapy within 14 days prior to the first dose of NUV-868.
• Received treatment with an investigational agent for any indication within 14 days for non-myelosuppressive agent, or within 21 days or < 5 half-lives (whichever is longer) for myelosuppressive agent, prior to the first dose of study treatment.
• Requires medications that are known to be strong (or moderate for olaparib) inducers and/or strong (or moderate for olaparib) inhibitors of CYP3A4/5 enzymes.

Other

• Female patients who are pregnant of breastfeeding.

• Recovered from toxicity to prior anticancer therapy
• Adequate bone marrow and organ function
• No known active or symptomatic central nervous system (CNS) disease
  • Cohort-Specific Inclusion Criteria: In addition to the inclusion criteria listed above, the following criteria apply for enrollment into specific cohorts.
  • Phase 1 (NUV-868 Monotherapy)
• Patients with advanced solid tumors that have progressed during or after treatment with approved therapies or for which there is no standard effective therapy available
• Life expectancy of > 3 months
• Eastern Cooperative Oncology Group Performance Status ≤ 2
• Measurable or non-measurable disease
  • Phase 1b (NUV-868 in Combination With Enzalutamide or Olaparib)
• Life expectancy of > 3 months
• Eastern Cooperative Oncology Group Performance Status ≤ 2
• (Select cohorts only) Measurable disease
• Patient must be able to read and write sufficiently to document food intake and study drug dosing on the Dosing Diary or must have a caregiver who is willing and able to complete the Dosing Diary with the patient.
• One of the following tumor types:
  • Ovarian: Platinum-resistant OR platinum-refractory high grade serous ovarian, fallopian, or primary peritoneal cancer in the relapsed setting
  • Pancreatic: Pancreatic ductal adenocarcinoma (PDAC) with progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting
  • Prostate: Histologically confirmed, metastatic adenocarcinoma of the prostate (adenocarcinoma/high grade carcinoma with neuroendocrine features is allowed) with progression on or after treatment with at least one NHT in the metastatic setting
  • Breast: Triple-negative breast cancer (TNBC) with progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting
  • Other advanced tumors (only Phase 1b dose escalation, NUV-868 + olaparib): the study Medical Monitor must approve enrollment.
  • For all tumor types: Patients will be allowed in the study regardless of their BRCA/HRR status.
  • Phase 2
• Life expectancy of > 6 months
• (Select cohorts only): At least one measurable lesion defined by standard criteria
• Eastern Cooperative Oncology Group Performance Status ≤ 1
• One of the following tumor types:
  • Ovarian: Platinum-resistant or platinum- refractory high grade serous ovarian, fallopian, or primary peritoneal cancer in the relapsed setting
  • Pancreatic: Progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting
  • Prostate: Histologically confirmed, metastatic adenocarcinoma of the prostate (adenocarcinoma/high grade carcinoma with neuroendocrine features is allowed) with progression on or after treatment with at least one NHT in the metastatic setting
  • Breast: TNBC with progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting