Study of AMG 650 in Adult Participants With Advanced Solid Tumors

NCT04293094 | Completed Phase 1 FDA Drug

• 1 other identifier: 20190131
• Study Type: interventional
• Target: 66
• Locations: 7 countries
• Sites: 22

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).

Conditions

Advanced Solid Tumors

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)

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (10)

• 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

Study Arms (3)

Dose Exploration Phase

EXPERIMENTAL

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

Dose Expansion Phase Group 1: TNBC

EXPERIMENTAL

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

Dose Expansion Phase Group 2: HGSOC

EXPERIMENTAL

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

Interventions

AMG 650 DRUG

AMG 650 administered orally as a tablet.

Dose Expansion Phase Group 1: TNBC; Dose Expansion Phase Group 2: HGSOC; Dose Exploration Phase

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Volastra Therapeutics, Inc.: lead
• Amgen: collaborator

Study Sites (22)

The Angeles Clinic and Research Institute, West Los Angeles Office

Los Angeles, California, 90025, United States

Location

Sarcoma Oncology Research Center LLC

Santa Monica, California, 90403, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110-1093, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Laura and Isaac Perlmutter Cancer Center at New York University Langone

New York, New York, 10016, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology - Baylor

Dallas, Texas, 75246, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z5, Canada

Location

IRCCS Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Aichi Cancer Center

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28009, Spain

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 3, 2020
• Study Start: March 11, 2020
• Primary Completion: October 24, 2022
• Study Completion: February 15, 2023
• Last Updated: August 24, 2023

Record last verified: 2023-08

Locations

AU (2); BE (1); IT (1); CA (2); ES (1); US (13); JP (2)