Study of AMG 650 in Adult Participants With Advanced Solid Tumors

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

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).

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: AMG 650

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter Maccallum Cancer Centre
• Belgium
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven - Campus Gasthuisberg
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Princess Margaret Cancer Centre
• Italy
  • Milano, Italy, 20141
    • IRCCS Istituto Europeo di Oncologia
• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 464-8681
      • Aichi Cancer Center
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
• Spain
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon
• United States
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute, West Los Angeles Office
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Research Center LLC
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1093
      • Washington University
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center at New York University Langone
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Exploration Phase; 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; AMG 650 administered orally as a tablet.
Experimental: Dose Expansion Phase Group 1: TNBC; 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; AMG 650 administered orally as a tablet.
Experimental: Dose Expansion Phase Group 2: HGSOC; 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; AMG 650 administered orally as a tablet.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	Up to 24 months
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
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

Collaborators and Investigators

• Sponsor: Volastra Therapeutics, Inc.
• Collaborators: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2020
• Primary Completion (Actual): October 24, 2022
• Study Completion (Actual): February 15, 2023

Study Registration Dates

• First Submitted: March 2, 2020
• First Submitted That Met QC Criteria: March 2, 2020
• First Posted (Actual): March 3, 2020

Study Record Updates

• Last Update Posted (Actual): August 24, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: p53 mutation; Triple negative breast cancer (TNBC); AMG 650; Locally-advanced/metastatic solid tumors; Serous like endometrial cancers; High grade serous ovarian cancer (HGSOC)
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 20190131

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No