Clinical Trial 23378

• Overview

  Study Title:

  A phase 1/2, first-in-human study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity of AVZO-021 as a single agent and in combination therapy in patients with advanced solid tumors

  Objective:

  Phase 1 - Dose Escalation: Primary Objectives: * To characterize the safety and tolerability of AVZO-021 * To determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of AVZO-021 Secondary Objectives: * To assess preliminary antitumor activity, as assessed by investigator using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * To characterize the plasma pharmacokinetic (PK) properties of AVZO-021 and its metabolite AL-200627 in monotherapy and in combination therapy. * To evaluate the effect of a high-fat meal on the PK of AVZO-021 Phase 2 - Dose Expansion: Primary Objectives: * To assess the antitumor activity of AVZO-021 as assessed by blinded independent central review (BICR) using RECIST v1.1 Secondary Objectives: * To characterize the safety and tolerability of AVZO-021 * To characterize the plasma PK properties of AVZO-021 and its metabolite AL-200627 in monotherapy and in combination therapy.

• Treatments

  Therapies:

  Antibody-Drug Conjugate; CDK2 Inhibitor; CDK4/6 Inhibitor; Chemotherapy (NOS); Hormonal Therapy

  Medications:

  772256 (Palbociclib); AVZO-021 (); Abemaciclib (); Faslodex (fulvestrant); Femara (Letrozole); LEE011 (Ribociclib); LY2835219 (Abemaciclib); Letrozole (); Palbociclib (); Paraplatin (carboplatin); Ribociclib (); Sacituzumab Govitecan (); carboplatin (); fulvestrant ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • 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.
  • Ability to swallow capsules or tablets.

• Exclusion Criteria

  Key Exclusion Criteria:
  • 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.
  • Active CNS metastases or confirmed leptomeningeal disease are not eligible.
  • Unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade >1 at the time of starting study treatment.
  • Clinically unstable cardiac function as described in the protocol.
  • Any active or chronic infection/disease that compromises the immune system.
  • Current treatment with strong or moderate cytochrome P450 (CYP)3A4 inhibitors or inducers.
  • Active second malignancy unless in remission with life expectancy > 2 years and with documented sponsor approval.
  • Pregnancy, lactation, or plans to breastfeed during the study or within 6 months of the last dose of study intervention.

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