Study of AMG 650 in Adult Participants With Advanced Solid Tumors

Sponsor

Amgen (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04293094

Collaborator

(none)

140

Enrollment

Locations

Arms

48.5

Anticipated Duration (Months)

6.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: AMG 650	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

140 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 11, 2020

Anticipated Primary Completion Date :

Oct 24, 2022

Anticipated Study Completion Date :

Mar 26, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

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