This study, the first clinical trial of AVZO-021, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and anti-tumor effects of AVZO-021 in patients with advanced solid tumors. AVZO-021 is an oral medication that inhibits cyclin-dependent kinase 2 (CDK 2).
Male or female aged ≥18 years old at screening with Eastern Cooperative Oncology Group (ECOG) 0-1.
No more than 2 prior cytotoxic chemotherapy regimens for locally advanced/metastatic disease (excepting patients treated with an antibody-drug conjugate, with ovarian cancer if there disease is platinum resistant or refractory, having progressed beyond all SOC care; and patients who have received prior chemotherapy in the adjuvant or neoadjuvant setting >12 months prior to starting AVZO-021 treatment).
Measurable disease as determined by RECIST version 1.1.
Adequate bone marrow and organ function.
Received an investigational agent or anticancer therapy within 2 weeks, or 5 half-lives of the drug, whichever is shorter, prior to planned start of AVZO-021.
Received any CDK2 inhibitor, protein kinase membrane associated tyrosine/threonine 1 (PKMYT1) inhibitor, or WEE1 inhibitor anticancer therapy. For cohort B5, prior therapy with topoisomerase inhibitors is not permitted.
Undergone major surgery within 4 weeks prior to planned start of AVZO-021.
Received radiotherapy for palliation within 7 days of the first dose of study treatment, unless specified otherwise in the protocol.
Sequential
AVZO-021
DrugAVZO-021 is a selective and potent oral inhibitor of CDK2 being developed for the treatment of patients with advanced solid tumors with CDK2 dependency (1A), CCNE1 amplified solid tumors (2A), HR+/HER2- BC (1B1-1B5, 2B1-2B5) and CCNE1 amplified EOC (1C, 2C)
Palbociclib
DrugAntineoplastic agent, cyclin-dependent kinase 4/6 inhibitor
Fulvestrant
DrugAntineoplastic agent, estrogen receptor antagonist
Letrozole
DrugAntineoplastic agent, aromatase inhibitor
Ribociclib
DrugAntineoplastic CDK4/6 inhibitor
Abemaciclib
DrugAntineoplastic CDK4/6 inhibitor
Carboplatin
DrugAlkylating agent
Sacituzumab Govitecan-hziy
DrugTrop-2 antibody and topoisomerase inhibitor
Occurrence of Dose Limiting Toxicities (DLTs) during the first cycle (Phase 1)
Number of participants with DLTs assessed for severity using CTCAE v5.0 criteria will be summarized by dose level.
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 1)
To evaluate the type, incidence, severity, timing, seriousness, and relationship to study treatment of adverse events and any laboratory abnormalities summarized by dose level.
Determination of Recommended Phase 2 Dose (RP2D) (Phase 1)
RP2D for AVZO-021 is less than or the same as the maximum tolerated dose (MTD) as defined by the occurrence of DLTs and TEAEs calculated using isotonic regression.
Objective Response Rate (ORR) (Phase 2)
Defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR), as determined by the investigator by radiographic disease assessment according to RECIST v1.1.
PK Parameters: Maximum plasma concentration (Cmax) (monotherapy and combination)
PK Parameters: Time to maximum plasma concentration (Tmax) (monotherapy and combination)
PK Parameters: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC 0-last) (monotherapy and combination)
PK Parameters: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC 0-tau) (monotherapy and combination)
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