Advanced Solid Tumors
Conditions
Keywords
AMG 650, Locally-advanced/metastatic solid tumors, p53 mutation, Serous like endometrial cancers, Triple negative breast cancer (TNBC), High grade serous ovarian cancer (HGSOC)
Brief summary
To evaluate the safety and tolerability of AMG 650 in adult participants and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
Interventions
DRUGAMG 650
AMG 650 administered orally as a tablet.
Sponsors
Amgen
Volastra Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Male and female ≥ 18 years old * Triple Negative Breast Cancer participants only: Participant must have histologically or cytologically confirmed metastatic or locally recurrent estrogen receptor (ER)-negative (\<1% by immunohistochemistry \[IHC\]), progesterone receptor (PR)-negative (\<1% IHC) and human epidermal growth factor receptor 2 (Her2)-negative (either fluorescent in situ hybridisation \[FISH\] negative, 0 or 1+ by IHC, or IHC2+ and FISH negative per ASCO/CAP definition) breast cancer. Participant must be relapsed/refractory to at least one line of systemic chemotherapy in the metastatic setting (excluding neoadjuvant or adjuvant chemotherapies) or intolerant of existing therapy(ies) known to provide clinical benefit or have no other available treatment options. Prior exposure to an immune checkpoint inhibitor is allowed. * Platinum-Resistant High Grade Serous Ovarian Cancer, primary peritoneal cancer and/or fallopian-tube cancer participants only: Participant must have histologically or cytologically confirmed diagnosis of metastatic or unresectable high grade serous ovarian cancer, with platinum-resistance defined as progression during or within 6 months of a platinum-containing regimen, with no other treatment option available. Prior exposure to platinum-resistant recurrence therapy is allowed. * Serous Endometrial Cancer participants only (Dose Exploration only): Participant must have histologically or cytologically confirmed diagnosis of metastatic or recurrent serous endometrial cancer, and be relapsed/refractory to at least one line of systemic therapy in the metastatic/recurrent setting or intolerant of existing therapy(ies) known to provide clinical benefit for their condition. * Participants with advanced or metastatic solid tumor with TP53MUT (Dose Exploration only, as assessed by local testing) that is unresectable and relapsed/refractory to at least one line of systemic chemotherapy or intolerant. * TNBC participants only (Dose Expansion): Progressed on no more than 3 prior lines of systemic therapy for locally advanced or metastatic disease (not including adjuvant or neo-adjuvant). Systemic therapy with poly ADP ribose polymerase (PARP) inhibitor will be counted as one line of therapy. * HGSOC participants only (Dose Expansion): Progressed on no more than 5 prior lines of systemic therapy for locally advanced or metastatic disease (not including adjuvant or neo-adjuvant). Systemic therapy with (PARP) inhibitor will be counted as one line of therapy. Induction followed by maintenance will be counted as one line of therapy.
Exclusion criteria
* Untreated or symptomatic brain metastases and leptomeningeal disease (exception: benign asymptomatic tumors are permitted). * Current primary CNS tumor, hematological malignancies or lymphoma. * Uncontrolled pleural effusions(s), pericardial effusion, or ascites. * Gastrointestinal (GI) tract disease causing the inability to take oral medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Dose Limiting Toxicities (DLTs) | Up to 12 months |
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) | Up to 24 months |
| Number of Participants with Serious Adverse Events (SAEs) | Up to 24 months |
| Number of Participants with Treatment-related Adverse Events | Up to 24 months |
| Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Sign Measurement | Up to 24 months |
| Number of Participants Who Experience a Clinically Significant Change from Baseline in Electrocardiogram (ECGs) Measurement | Up to 24 months |
| Number of Participants Who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Tests | Up to 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) | Up to 24 months |
| Time to Maximum Plasma Concentration (Tmax) of AMG 650 | Up to 24 months |
| Progression-free Survival (PFS) | Up to 24 months |
| Duration of Response (DOR) | Up to 24 months |
| Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval for AMG 650 | Up to 24 months |
| Clinical Benefit Rate (CBR) | Up to 24 months |
| Time to Response (TTR) | Up to 24 months |
| Time to Progression (TTP) | Up to 24 months |
| Overall Survival (OS) | Up to 24 months |
| Maximum Plasma Concentration (Cmax) of AMG 650 | Up to 24 months |
Countries
Australia, Belgium, Canada, Italy, Japan, Spain, United States
Outcome results
None listed