QUILT-3.031: AMG 337 in Subjects With Advanced or Metastatic Clear Cell Sarcoma

A Phase 2 Study of AMG 337 in Subjects With Advanced or Metastatic Clear Cell Sarcoma That Contains the Ewing Sarcoma Breakpoint Region 1-activating Transcription Factor-1 (EWSR1-ATF1) Gene Fusion

This is a phase 2 study that will assess the efficacy of AMG 337 in subjects with advanced or metastatic clear cell sarcoma that contains the EWSR1-ATF1 gene fusion.

Study Overview

• Status: Terminated
• Conditions: Clear Cell Sarcoma
• Intervention / Treatment: Drug: AMG 337

Detailed Description

The phase 2 single arm study will assess efficacy of AMG 337 (based on confirmed ORR) in subjects with advanced or metastatic clear cell sarcoma that contains the EWSR1-ATF1 gene fusion, as determined by fluorescent in situ hybridization (FISH) or other diagnostic methods and confirmed by RNA sequencing (RNAseq).

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • El Segundo, California, United States, 90245
      • Chan Soon-Shiong Institute for Medicine
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas, MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
2. Able to attend required study visits and return for adequate follow-up, as required by this protocol.
3. Able to self-administer AMG 337 as a whole capsule by mouth every day.
4. Age ≥ 16 years.
5. Histologically confirmed, unresectable, locally advanced or metastatic tumors that contain the EWSR1-ATF1 gene fusion, as determined by fluorescent in situ hybridization (FISH) or other diagnostic methods and confirmed by RNA sequencing (RNAseq).
6. Have measurable disease evaluable in accordance with RECIST Version 1.1.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
8. Must have a recent Formalin-fixed paraffin-embedded (FFPE) tumor biopsy specimen that was obtained following the conclusion of the most recent anticancer treatment. If an historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period.
9. Must be willing to undergo a biopsy during the treatment period, if considered safe by the investigator.
10. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.

11. Hematologic function, as follows:

    1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.
    2. Platelet count ≥ 50 × 109/L.
    3. Hemoglobin > 8 g/dL.
    4. Prothrombin time (PT) or partial thromboplastin time (PTT) < 1.5 × upper limit of normal (ULN), except for subjects on anticoagulation therapy for venous thromboembolism.

12. Renal function, as follows:

    a. Calculated creatinine clearance > 30 mL/min.

13. Hepatic function, as follows:

    1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 × ULN and total bilirubin < 1.5 × ULN.
    2. Alkaline phosphatase (ALP) < 2 × ULN (≤ 5 × ULN if bone or liver metastases are present)
14. Agreement to practice effective contraception (both male and female subjects, if the risk of conception exists).

Exclusion Criteria:

1. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
2. Inability to attend required study visits and return for adequate follow-up, as required for this protocol.
3. Known hypersensitivity to any component of the study medication(s).
4. Women who are nursing, pregnant, or planning to become pregnant during the duration of the study.

5. Current diagnosis or history of a second neoplasm, except the following:

   a. Adequately treated non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated with no evidence of disease for ≥ 2 years.

6. History of bleeding diathesis.
7. Uncontrolled hypertension (systolic > 160 mmHg and/or diastolic > 100 mmHg) or clinically significant cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months before study day 1; unstable angina; congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring medication.
8. Baseline ECG Fridericia's formula QTcF > 470 ms.
9. Active infection requiring intravenous (IV) antibiotics within 2 weeks before study day 1.
10. Significant gastrointestinal disorder (eg, Crohn's disease, ulcerative colitis, extensive gastrointestinal resection) that in the opinion of the Investigator may influence drug absorption.
11. Positive result of screening test for human immunodeficiency virus (HIV).
12. Evidence of acute hepatitis B and C. Subjects with chronic hepatitis B or C are eligible if their condition is stable and, in the opinion of the investigator, would not pose a risk to subject safety.

13. Toxicities from prior anti-tumor therapy not resolved to CTCAE Version 4.03 grade 0 or 1.

    a. Grade 2 toxicities from prior anti-tumor therapy that are considered irreversible (defined as having been present or stable for > 4 weeks), such as stable grade 2 peripheral neuropathy or ifosfamide-related proteinuria, may be allowed if they are not otherwise described in the exclusion criteria.

14. Participation in this study or in an investigational study and/or procedure with any molecularly targeted agents reported to inhibit Mesenchymal epithelial transition factor (MET) within 14 days before study day 1.
15. Anti-tumor therapy, including chemotherapy, antibody therapy, retinoid therapy, or other investigational therapy within 14 days before study day 1.
16. Therapeutic or palliative radiation therapy within 14 days before study day 1.
17. Major surgery within 28 days before study day 1.
18. Any comorbidity that in the opinion of the investigator may increase the risk of toxicity.
19. Concurrent or prior use of a strong CYP3A4 inhibitor within 14 days before study day 1, including the following: ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole.
20. Concurrent or prior ingestion of grapefruit or grapefruit products, or other foods known to inhibit CYP3A4 within 7 days before study day 1.
21. Concurrent or prior use of strong CYP3A4 inducers within 28 days before study day 1, including the following: phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, or the herbal supplement St. John's Wort.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMG 337; AMG 337 will be administered in patients with advanced or metastatic clear cell sarcoma	Drug: AMG 337; 6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one•hydrate (1:1)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Confirmed ORR (confirmed complete response or partial response) will be evaluated in accordance with RECIST Version 1.1 by BICR.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events (Safety And Tolerability)	To evaluate the safety of AMG 337 based on grade 3 or 4 non-hematologic toxicity.	1 year
Progression-free Survival (PFS)	To determine PFS, evaluated in accordance with RECIST Version 1.1 BICR.	1 year
Overall Survival (OS)	To determine OS, defined as the time from the date of the first administration of therapy to the date of death.	1 year
Duration of Response (DOR)	To determine DOR, measured by RECIST Version 1.1 by BICR.	1 year
Disease Control Rate (DCR)	To determine DCR (confirmed CR, PR, or SD) lasting for at least 4 months by BICR.	4 months

Collaborators and Investigators

• Sponsor: NantPharma, LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2018
• Primary Completion (Actual): August 13, 2021
• Study Completion (Actual): September 21, 2021

Study Registration Dates

• First Submitted: April 20, 2017
• First Submitted That Met QC Criteria: April 26, 2017
• First Posted (Actual): April 27, 2017

Study Record Updates

• Last Update Posted (Estimate): December 13, 2022
• Last Update Submitted That Met QC Criteria: December 9, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Sarcoma; Sarcoma, Clear Cell
• Other Study ID Numbers: QUILT-3.031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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