Clinical trial NCT04293094: Study of AMG 650 in Adult Participants With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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)
Lead sponsor: Volastra Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2020-03-03
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Dose Limiting Toxicities (DLTs)
timeFrame: Up to 12 months
measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 24 months
measure: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Up to 24 months
measure: Number of Participants with Treatment-related Adverse Events
timeFrame: Up to 24 months
measure: Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Sign Measurement
timeFrame: Up to 24 months
measure: Number of Participants Who Experience a Clinically Significant Change from Baseline in Electrocardiogram (ECGs) Measurement
timeFrame: Up to 24 months
measure: Number of Participants Who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Tests
timeFrame: Up to 24 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 24 months
measure: Duration of Response (DOR)
timeFrame: Up to 24 months
measure: Progression-free Survival (PFS)
timeFrame: Up to 24 months
measure: Clinical Benefit Rate (CBR)
timeFrame: Up to 24 months
measure: Time to Response (TTR)
timeFrame: Up to 24 months
measure: Time to Progression (TTP)
timeFrame: Up to 24 months
measure: Overall Survival (OS)
timeFrame: Up to 24 months
measure: Maximum Plasma Concentration (Cmax) of AMG 650
timeFrame: Up to 24 months
measure: Time to Maximum Plasma Concentration (Tmax) of AMG 650
timeFrame: Up to 24 months
measure: Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval for AMG 650
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute, West Los Angeles Office
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center LLC
state: California
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at New York University Langone
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology - Baylor
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Campus Gasthuisberg
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Milano
country: Italy
facility: IRCCS Istituto Europeo di Oncologia
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
Study officials:
References: