Phase 1/2 Safety and Efficacy Study of NUV-868 as Monotherapy and in Combination With Olaparib or Enzalutamide in Adult Patients With Advanced Solid Tumors

NUV-868-01 is a first-in human, open- label, Phase 1/2 dose escalation and expansion study in
patients with advanced solid tumors. The Phase 1 and 1b portions include patients with
advanced solid tumors and are designed to determine the safety and the dose(s) of NUV-868 to
be used as monotherapy and in combination with olaparib or enzalutamide for the Phase 2
portion. In Phase 2, NUV-868 in combination with olaparib or enzalutamide will be given to
determine the safety and efficacy of these study treatments. One cohort of patients (with
enzalutamide-naïve metastatic castration-resistant prostate cancer) will be randomized to
receive either NUV-868 monotherapy, enzalutamide monotherapy, or the combination of NUV-868 +
enzalutamide. Patients will self-administer NUV-868 orally daily in 28-day cycles as
monotherapy in Phases 1 and 2. In Phases 1b and 2, patients will self-administer NUV-868
orally daily in 28-day cycles in combination with olaparib or enzalutamide daily at standard
prescribed doses (Phase 1b) or at the recommended Phase 2 combination dose (RP2cD) that is
determined in Phase 1b. Patients will be treated until disease progression, toxicity,
withdrawal of consent, or termination of the study.

Key Inclusion Criteria For All Phases and Cohorts:

1. Recovered from toxicity to prior anticancer therapy

2. Adequate bone marrow and organ function

3. 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)

1. 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

2. Life expectancy of > 3 months

3. Eastern Cooperative Oncology Group Performance Status ≤ 2

4. Measurable or non-measurable disease

Phase 1b (NUV-868 in Combination With Enzalutamide or Olaparib)

1. Life expectancy of > 3 months

2. Eastern Cooperative Oncology Group Performance Status ≤ 2

3. (Select cohorts only) Measurable disease

4. 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.

5. One of the following tumor types:

1. Ovarian: Platinum-resistant OR platinum-refractory high grade serous ovarian,
fallopian, or primary peritoneal cancer in the relapsed setting

2. Pancreatic: Pancreatic ductal adenocarcinoma (PDAC) with progression on or after
treatment with at least one line of systemic chemotherapy in the advanced setting

3. 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

4. Breast: Triple-negative breast cancer (TNBC) with progression on or after
treatment with at least one line of systemic chemotherapy in the advanced setting

5. Other advanced tumors (only Phase 1b dose escalation, NUV-868 + olaparib): the
study Medical Monitor must approve enrollment.

6. For all tumor types: Patients will be allowed in the study regardless of their
BRCA/HRR status.

Phase 2

1. Life expectancy of > 6 months

2. (Select cohorts only): At least one measurable lesion defined by standard criteria

3. Eastern Cooperative Oncology Group Performance Status ≤ 1

4. One of the following tumor types:

1. Ovarian: Platinum-resistant or platinum- refractory high grade serous ovarian,
fallopian, or primary peritoneal cancer in the relapsed setting

2. Pancreatic: Progression on or after treatment with at least one line of systemic
chemotherapy in the advanced setting

3. 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

4. Breast: TNBC with progression on or after treatment with at least one line of
systemic chemotherapy in the advanced setting

Key Exclusion Criteria For All Phases and Cohorts:

1. 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.

2. 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.

3. 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.

4. Female patients who are pregnant of breastfeeding.