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

Phase 1

Not yet recruiting

• Conditions: Advanced Solid Tumors; Breast Cancer; Breast Carcinoma; Breast Neoplasms; ER Positive Breast Cancer; Cervical Cancers; Cervical Neoplasms; Cervical Carcinoma; Triple Negative Breast Cancer; Gynecologic Cancers
• Interventions: Drug: ATV-1601; Combination Product: ATV-1601 + Fulvestrant

• Registration Number: NCT07038369
• Lead Sponsor: Atavistik Bio, Inc

Brief Summary

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.

Detailed Description

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 Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-18
• Study First Submitted QC: 2025-06-18
• Last Update Submitted: 2025-06-18
• Study First Posted: 2025-06-26
• Last Update Posted: 2025-06-26
• Study Start: 2025-07-01
• Primary Completion: 2028-08-31
• Study Completion: 2029-01-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 134

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental/Part 1a: ATV-1601	ATV-1601	ATV-1601
Experimental/Part 1b: ATV-1601 + Fulvestrant	ATV-1601 + Fulvestrant	ATV-1601 + Fulvestrant

Primary Outcome Measures

Name	Time	Method
Escalation: Maximum tolerated dose and/or recommended phase 2 dose of ATV-1601 monotherapy and in combination with fulvestrant	Approximately 48 months.	Number of patients with dose-limiting toxicities.
Escalation & Expansion: Safety and Tolerability of monotherapy and in combination with fulvestrant	Approximately 48 months.	Rate and severity of adverse events, laboratory findings, and Electrocardiogram results.
Expansion: Maximum and minimum plasma concentration	Approximately 48 months.	Drug concentration in Blood.
Expansion: Time to C Max	Approximately 48 months	Drug concentration in Blood
Expansion: Area under the concentration-time curve	Approximately 48 months	Drug concentration in Blood
Expansion: AUC at end of dosing interval	Approximately 48 months	Drug concentration in Blood
Expansion: AUC extrapolated to infinity	Approximately 48 months	Drug concentration in Blood
Expansion: Half-life	Approximately 48 months	Drug concentration in Blood
Expansion: Trough Concentrations	Approximately 48 months	Drug concentration in Blood

Secondary Outcome Measures

Name	Time	Method
Escalation: Trough Concentrations	Approximately 48 months	Drug concentration in Blood
Escalation & Expansion: Objective response rate	Approximately 48 months	Tumor measurements by RECIST 1.1
Escalation: Maximum and minimum plasma concentration	Approximately 48 months.	Drug concentration in Blood.
Escalation: Time to C max	Approximately 48 months	Drug concentration in Blood
Escalation: Area under the concentration-time curve	Approximately 48 months	Drug concentration in Blood
Escalation: AUC at end of dosing interval	Approximately 48 months	Drug concentration in Blood
Escalation: AUC extrapolated to infinity	Approximately 48 months	Drug concentration in Blood
Escalation: Half-life	Approximately 48 months	Drug concentration in Blood
Escalation & Expansion: Duration of Response	Approximately 48 months	Tumor measurements by RECIST 1.1
Escalation & Expansion: Clinical Benefit Rate	Approximately 48 months	Tumor measurements by RECIST 1.1
Expansion: Progression Free Survival	Approximately 48 months	Tumor measurements by RECIST 1.1

Trial Locations

Locations (1)

Study Center; 🇺🇸 Houston, Texas, United States