Study of AMG 650 in Adult Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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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).

Official Title
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A Phase 1, Multicenter, Open-label, Dose-Exploration and Dose-Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 650 in Subjects With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: AMG 650


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Exploration Phase<br>Participants will receive AMG 650 in 1 of 3 alternative schedules. The maximum tolerated dose (MTD) of each schedule will be estimated using isotonic regression (Ji et al, 2010). The Recommended Phase 2 Dose (RP2D) may be identified based on emerging safety, efficacy, and pharmacodynamics (PD) data prior to reaching an MTD. | Drug: AMG 650<br>* AMG 650 administered orally as a tablet.<br>|
| Experimental: Dose Expansion Phase Group 1: TNBC<br>Participants with locally advanced or metastatic triple negative breast cancer (TNBC), will be administered with the preliminary RP2D identified from the dose exploration part of the study. | Drug: AMG 650<br>* AMG 650 administered orally as a tablet.<br>|
| Experimental: Dose Expansion Phase Group 2: HGSOC<br>Participants with locally advanced or metastatic high grade serous ovarian cancer (HGSOC), will be administered with the preliminary RP2D identified from the dose exploration part of the study. | Drug: AMG 650<br>* AMG 650 administered orally as a tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) |  | Up to 24 months | 
| Duration of Response (DOR) |  | Up to 24 months | 
| Progression-free Survival (PFS) |  | 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 | 
| Time to Maximum Plasma Concentration (Tmax) of AMG 650 |  | Up to 24 months | 
| Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval for AMG 650 |  | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMG 650, Locally-advanced/metastatic solid tumors, p53 mutation, Serous like endometrial cancers, Triple negative breast cancer (TNBC), High grade serous ovarian cancer (HGSOC)