A Phase 1 Study of ATV-1601 in Patients With Advanced Cancer That Have AKT1 E17K Mutations

Phase 1RecruitingNCT07038369

Atavistik Bio, Inc134 enrolled

Overview

This is a Phase 1, open-label study to evaluate the safety and tolerability of ATV-1601 administered orally in adults with AKT1 E17K-mutant, advanced solid tumors and also in HR+/HER2- advanced and metastatic breast cancer, with or without fulvestrant.

This is a first-in-human, open-label, multicenter, Phase 1a/1b dose escalation dose finding, and dose expansion study to evaluate safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of ATV-1601 as monotherapy in participants with advanced or metastatic solid tumors with the AKT1 E17K mutation, and in combination with fulvestrant in participants with breast cancer that has the AKT1 E17K mutation. This study has a dose escalation and expansion phase with ATV-1601, and an escalation and expansion phase in combination with Fulvestrant.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

134

Conditions

Advanced Solid Tumors Breast Cancer Breast Carcinoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Histologically or cytologically confirmed metastatic or advanced-stage solid malignant tumor or HR+/HER2- breast cancer. 2. Have progressed on, were intolerant to, or experienced disease recurrence after standard therapy and have no available effective or tolerable treatment options to derive clinically meaningful benefit. 3. Tumor must have documented specific mutation profile as outlined below based on local laboratory testing. 4. Participants with solid tumors or HR+/HER2- breast cancer with AKT1 E17K mutations. 5. Measurable disease according to RECIST v1.1 criteria. 6. Formalin-fixed paraffin-embedded tumor specimen available for submission. 7. Eastern Cooperative Oncology Group performance status of 0 or 1. Exclusion Criteria: 1. Previously documented activating mutations in KRAS, NRAS, HRAS, or BRAF. 2. Inadequate bone marrow reserve or organ function. 3. Clinically significant abnormalities of glucose metabolism. 4. Participants who are symptomatic or have uncontrolled brain metastases. 5. Requires treatment with certain medications. Participants must meet other inclusion/exclusion criteria.

Locations (13)

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

RECRUITING

Florida Cancer Specialists & Research Institute - Lake Mary

Lake Mary, Florida, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

RECRUITING

Washington University

St Louis, Missouri, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

RECRUITING

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

RECRUITING

Centre Leon Berard

Lyon, France

RECRUITING

National Cancer Centre Singapore

Singapore, Singapore

RECRUITING

...and 3 more locations

Outcomes

Primary Outcomes

Expansion: Maximum and minimum plasma concentration

Drug concentration in Blood.

Time frame: Approximately 48 months.

Expansion: Time to C Max

Drug concentration in Blood

Time frame: Approximately 48 months

Expansion: Area under the concentration-time curve

Drug concentration in Blood

Time frame: Approximately 48 months

Expansion: AUC at end of dosing interval

Drug concentration in Blood

Time frame: Approximately 48 months

Expansion: AUC extrapolated to infinity

Drug concentration in Blood

Time frame: Approximately 48 months

Expansion: Half-life

Drug concentration in Blood

Time frame: Approximately 48 months

Expansion: Trough Concentrations

Drug concentration in Blood

Time frame: Approximately 48 months

Escalation & Expansion: Safety and Tolerability of monotherapy.

Number of participants with Treatment Emergent Adverse Events (TEAEs). Safety will be assessed by monitoring adverse events, laboratory tests and ECG results.

Time frame: Approximately 48 months.

Escalation: Maximum tolerated dose and/or recommended phase 2 dose of ATV-1601 in monotherapy.

Number of patients with dose-limiting toxicities.

Time frame: Approximately 48 months.

Escalation: Maximum tolerated dose and/or recommended phase 2 dose of ATV-1601 combination with fulvestrant.

Number of patients with dose-limiting toxicities.

Time frame: Approximately 48 months.

Secondary Outcomes

Escalation: Maximum and minimum plasma concentration

Drug concentration in Blood.

Time frame: Approximately 48 months.

Escalation: Time to C max

Drug concentration in Blood

Time frame: Approximately 48 months

Escalation: Area under the concentration-time curve

Drug concentration in Blood

Time frame: Approximately 48 months

Escalation: AUC at end of dosing interval

Drug concentration in Blood

Time frame: Approximately 48 months

Escalation: AUC extrapolated to infinity

Drug concentration in Blood

Time frame: Approximately 48 months

Escalation: Half-life

Drug concentration in Blood

Time frame: Approximately 48 months

Escalation: Trough Concentrations

Drug concentration in Blood

Time frame: Approximately 48 months

Escalation & Expansion: Objective response rate

Tumor measurements by RECIST 1.1

Time frame: Approximately 48 months

Escalation & Expansion: Duration of Response

Tumor measurements by RECIST 1.1

Time frame: Approximately 48 months

Escalation & Expansion: Clinical Benefit Rate

Tumor measurements by RECIST 1.1

A Phase 1 Study of ATV-1601 in Patients With Advanced Cancer That Have AKT1 E17K Mutations

Overview

Conditions

Interventions

Eligibility

Locations (13)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts