Advanced Solid Tumors, Breast Cancer, Breast Carcinoma, Breast Diseases, Breast Neoplasms, Cervical Cancers, Cervical Carcinoma, Cervical Neoplasms, Endometrial Cancer, Endometrial Carcinoma (EC), Endometrial Neoplasm, ER Positive Breast Cancer, Fallopian Cancer, Genital Neoplasms, Female, Gynecologic Cancers, Gynecologic Neoplasm, Neoplasms, Neoplasms by Site, Ovarian Cancer, Ovarian Carcinoma, Ovarian Neoplasms, Prostate Cancers, Prostate Carcinoma, Solid Tumors, Triple Negative Breast Cancer, Urogenital Neoplasms, Uterine Neoplasms
Conditions
Keywords
AKT mutation, Mutant AKT, AKT1 mutation, AKT mutant, Gynecologic carcinoma, Fallopian Carcinoma, Fallopian Neoplasm, HR positive breast, AKT Gene Mutation, AKT1 E17K
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.
Interventions
DRUGATV-1601
Drug: ATV-1601 • Oral ATV-1601
COMBINATION_PRODUCTATV-1601 + Fulvestrant
Drug: ATV-1601 * Oral ATV-1601 Drug: Fulvestrant * Intramuscular Injection
Sponsors
Atavistik Bio, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Escalation & Expansion: Safety and Tolerability of monotherapy. | Approximately 48 months. | Number of participants with Treatment Emergent Adverse Events (TEAEs). Safety will be assessed by monitoring adverse events, laboratory tests and ECG results. |
| Escalation: Maximum tolerated dose and/or recommended phase 2 dose of ATV-1601 in monotherapy. | Approximately 48 months. | Number of patients with dose-limiting toxicities. |
| Escalation: Maximum tolerated dose and/or recommended phase 2 dose of ATV-1601 combination with fulvestrant. | Approximately 48 months. | Number of patients with dose-limiting toxicities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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: Trough Concentrations | Approximately 48 months | Drug concentration in Blood |
| Escalation & Expansion: Objective response rate | Approximately 48 months | Tumor measurements by RECIST 1.1 |
| 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 |
Countries
France, Singapore, Spain, United States
Contacts
STUDY_DIRECTORStudy Director
Atavistik Bio
Outcome results
None listed