Study of AVZO-021 in Patients With Advanced Solid Tumors

Key Inclusion Criteria:

1. Male or female aged ≥18 years old at screening with Eastern Cooperative OncologyGroup (ECOG) 0-1.

2. Disease-related inclusion criteria by study phase and part: i) Phase 1a Monotherapy Dose Escalation: Patients with locally advanced ormetastatic HR+/HER2- breast cancer, CCNE1-amplified tumors that are eitherepithelial ovarian cancer, primary peritoneal cancer, fallopian tube cancer,endometrial cancer or TNBC, with no other oncogenic driver mutations that aretreatable and standard therapies are no longer effective, appropriate, or safe inthe opinion of the investigator and medical monitor. Patients with any additionaltumor type with CCNE1 amplification can be enrolled only if clinical data issupportive and approved by medical monitor (Cohort 1A). ii) Phase 1b Combination Dose Escalation: histologically or cytologically confirmeddiagnosis of locally advanced or metastatic HR+ HER2- (HER2-low may be allowed iffailed standard of care therapy) breast cancer, who have been previously treatedwith inhibitor of CDK4/6 and endocrine therapy(Cohorts 1B1, 1B2, 1B3, 1B4, and 1B5);or histologically or cytologically confirmed diagnosis of CCNE1- amplified, locallyadvanced or metastatic, platinum-refractory or platinum-resistant EOC, primaryperitoneal, or fallopian tube cancer (Cohort 1C). iii) Phase 2a Monotherapy dose expansion: Histologically or cytologically confirmeddiagnosis of locally advanced or metastatic CCNE1 amplified epithelial ovariancancer, primary peritoneal cancer, fallopian tube cancer, endometrial cancer orTNBC, with no other oncogenic driver mutations that are treatable and standardtherapies are no longer effective, appropriate, or safe in the opinion of theinvestigator and medical monitor (Cohort 2A). iv) Phase 2b Combination dose expansion: Histologically or cytologically confirmeddiagnosis of locally advanced or metastatic HR+/HER2- (HER2-low may be allowed iffailed standard of care therapy) breast cancer who have been previously treated withno more than 1 prior CDK4/6 inhibitor and endocrine therapy (Cohorts 2B1, 2B2, 2B3, 2B4, and 2B5); or Histologically or cytologically confirmed diagnosis of locallyadvanced or metastatic, CCNE1-amplified, platinum-refractory or platinum-resistantEOC, primary peritoneal cancer, or fallopian tube cancer (Cohort 2C).

3. No more than 2 prior cytotoxic chemotherapy regimens for locally advanced/metastaticdisease (excepting patients treated with an antibody-drug conjugate, with ovariancancer if there disease is platinum resistant or refractory, having progressedbeyond all SOC care; and patients who have received prior chemotherapy in theadjuvant or neoadjuvant setting >12 months prior to starting AVZO-021 treatment).

4. Measurable disease as determined by RECIST version 1.1.

5. Adequate bone marrow and organ function.

6. Ability to swallow capsules or tablets.

Key Exclusion Criteria:

1. Received an investigational agent or anticancer therapy within 2 weeks, or 5half-lives of the drug, whichever is shorter, prior to planned start of AVZO-021.

2. Received any CDK2 inhibitor, protein kinase membrane associated tyrosine/threonine 1 (PKMYT1) inhibitor, or WEE1 inhibitor anticancer therapy. For cohort B5, priortherapy with topoisomerase inhibitors is not permitted.

3. Undergone major surgery within 4 weeks prior to planned start of AVZO-021.

4. Received radiotherapy for palliation within 7 days of the first dose of studytreatment, unless specified otherwise in the protocol.

5. Active CNS metastases or confirmed leptomeningeal disease are not eligible.

6. Unresolved toxicities from prior therapy greater than Common Terminology Criteriafor Adverse Events (CTCAE) version 5.0 Grade >1 at the time of starting studytreatment.

7. Clinically unstable cardiac function as described in the protocol.

8. Any active or chronic infection/disease that compromises the immune system.

9. Current treatment with strong or moderate cytochrome P450 (CYP)3A4 inhibitors orinducers.

10. Active second malignancy unless in remission with life expectancy > 2 years and withdocumented sponsor approval.

11. Pregnancy, lactation, or plans to breastfeed during the study or within 6 months ofthe last dose of study intervention.