DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumor (GIST)

NCT04276415 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: DS6157-A-U101
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 5

Brief Summary

This study will assess the safety, efficacy, and pharmacokinetics of DS-6157a in participants with advanced gastrointestinal stromal tumors (GIST).

Conditions

Gastrointestinal Stromal Tumors

Keywords

Gastrointestinal stromal tumors; DS-6157a; Anti-drug antibody conjugate; G-protein coupled receptor 20 (GPR20)

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Dose-limiting Toxicities (DLT) Following Intravenous Administration of DS-6157a in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)

  For hematologic toxicities, a DLT is defined as: Grade (Gr) 4 neutrophil count decreased lasting \>7 days, Gr ≥3 febrile neutropenia, Gr ≥3 anemia requiring transfusion, Gr 4 anemia, Gr 4 platelet count decreased, Gr ≥3 platelet count decreased lasting \>7 days or associated with clinically significant hemorrhage and/or requiring transfusion, and Gr 4 lymphocyte count decreased lasting ≥14 days. For non-hematologic, non-hepatic major organ toxicities, a DLT is all TEAEs of Gr ≥3 except: Gr 3 fatigue lasting \<7 days, Gr 3 nausea, vomiting, diarrhea, or anorexia that has resolved to Gr ≤2 within 3 days with maximal medical management, Gr 3 isolated lab findings not associated with signs or symptoms including alkaline phosphatase increased, hyperuricemia, serum amylase increased, and lipase increased, and Gr 3 hyponatremia lasting \<72 hours developed from Gr 1 at baseline. Symptomatic Gr 4 events were considered DLTs unless there was evidence it was associated with disease progression.

  Cycle 1 Day 1 to Day 21 (each cycle is 21 days)

• Number of Participants With Most Frequently Reported (≥10%) Any Grade Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-6157a in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)

  Treatment-emergent AEs (TEAEs) are adverse events with an onset date during the on-treatment period. Adverse events will be graded according to NCI CTCAE Version 5.0 and coded using the current version of Medical Dictionary for Regulatory Activities (MedDRA) version 24.1.

  Baseline up to 30 days after end of treatment, up to approximately 1 year 10 months post-treatment

• Objective Response Rate (ORR) Following Intravenous Administration of DS-6157a in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) (Dose Expansion)

  Baseline up to 5 years post-treatment

• Duration of Response (DoR) Following Intravenous Administration of DS-6157a in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) (Dose Expansion)

  Baseline up to 5 years post-treatment

• Disease Control Rate (DCR) Following Intravenous Administration of DS-6157a in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) (Dose Expansion)

  Baseline up to 5 years post-treatment

• Progression-free Survival (PFS) Following Intravenous Administration of DS-6157a in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) (Dose Expansion)

  Baseline up to 5 years post-treatment

Secondary Outcomes (16)

• Pharmacokinetic Analysis: Area Under the Plasma Concentration-time Curve up to the Last Quantifiable Time (AUClast) for DS-6157a and Total Anti-GPR20 Antibody Following Intravenous Administration of DS-6157a

  Cycle 1, Day 1: Predose, postdose, and 2 hours (hr), 4 hr, 7 hr postdose to Cycle 8, Day 1 predose (each cycle is 21 days)

• Pharmacokinetic Analysis: Area Under the Plasma Concentration-time Curve up to the Last Quantifiable Time (AUClast) for MAAA-1181a Following Intravenous Administration of DS-6157a

  Cycle 1, Day 1: Predose, postdose, and 2 hours (hr), 4 hr, 7 hr postdose to Cycle 8, Day 1 predose (each cycle is 21 days)

• Pharmacokinetic Analysis: Area Under the Plasma Concentration-time Curve in the Dosing Interval (AUCtau) for DS-6157a and Total Anti-GPR20 Antibody Following Intravenous Administration of DS-6157a

  Cycle 1, Day 1: Predose, postdose, and 2 hours (hr), 4 hr, 7 hr postdose to Cycle 8, Day 1 predose (each cycle is 21 days)

• Pharmacokinetic Analysis: Area Under the Plasma Concentration-time Curve in the Dosing Interval (AUCtau) for MAAA-1181a Following Intravenous Administration of DS-6157a

  Cycle 1, Day 1: Predose, postdose, and 2 hours (hr), 4 hr, 7 hr postdose to Cycle 8, Day 1 predose (each cycle is 21 days)

• Pharmacokinetic Analysis: Time to Maximum Plasma Concentration (Tmax) for DS-6157a, Total Anti-GPR20 Antibody, and MAAA-1181a Following Intravenous Administration of DS-6157a

  Cycle 1, Day 1: Predose, postdose, and 2 hours (hr), 4 hr, 7 hr postdose to Cycle 8, Day 1 predose (each cycle is 21 days)

Study Arms (3)

Dose Escalation: DS-6157a

EXPERIMENTAL

Participants with advanced gastrointestinal stromal tumor (GIST) who will receive an intravenous infusion of DS-6157a (escalating doses starting at 1.6 mg/kg).

Drug: DS-6157a

Dose Expansion: Cohort 1 (3rd line or later) treated at RDE

EXPERIMENTAL

Participants with advanced gastrointestinal stromal tumor (GIST) who have progressed on or are intolerant to imatinib (IM) and at least one post-IM treatment will receive DS-6157a at the recommended dose for expansion (RDE) based on the Dose Escalation phase.

Drug: DS-6157a

Dose Expansion: Cohort 2 (2nd line) treated at RDE

EXPERIMENTAL

Participants with advanced gastrointestinal stromal tumor (GIST) who have progressed on imatinib (IM) and had not received a post-IM treatment (2nd line) will receive DS-6157a at the recommended dose for expansion (RDE) based on the Dose Escalation phase.

Drug: DS-6157a

Interventions

DS-6157a DRUG

Administered as a single agent intravenously (IV) every 3 weeks

Dose Escalation: DS-6157a; Dose Expansion: Cohort 1 (3rd line or later) treated at RDE; Dose Expansion: Cohort 2 (2nd line) treated at RDE

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• At least 20 years old in Japan or 18 years old in other countries at the time of signature of the informed consent form (ICF), following local regulatory requirements
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Has histopathologically documented unresectable and/or metastatic GIST meeting the criteria below:
• Dose Escalation (Part 1): Participants should meet one of the following criteria:
• (For US sites only) Participants with GIST who have progressed on or are intolerant to imatinib (IM) and at least one post-IM treatment or who are not candidates for post-IM standard of care treatment
• (For Japan sites only) Participants with GIST who have received all the existing standard of care treatments or who are not candidates for one or more available post-IM standard of care treatments
• Participants with GIST who are not candidates for IM or curative intent surgical treatment (i.e., participants without activating KIT or platelet-derived growth factor receptor alpha (PDGFRa) mutations, with PDGFRa D842V mutations, or are KIT negative by local results)
• Dose Expansion (Part 2) Cohort 1: Participants with GIST who have progressed on or are intolerant to IM and at least one post-IM treatment
• Dose Expansion (Part 2) Cohort 2: Participants with GIST who have progressed on IM and had not received a post-IM treatment (2nd line)
• Consents to provide fresh tumor biopsy tissue samples both before and on DS-6157a treatment for the measurement of GPR20 levels by immunohistochemistry and other biomarkers
• Has a left ventricular ejection fraction (LVEF) ≥50% by either echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) within 28 days before study treatment
• Has at least 1 measurable lesion based on RECIST Version 1.1 as assessed by the Investigator
• Has adequate organ function within 7 days before the start of study treatment, defined as:
• Platelet count ≥100,000/mm\^3

You may not qualify if:

• History of an allogeneic bone marrow or solid organ transplant within 3 months before the start of study treatment
• Concomitant treatment with any medication that is classified as having a known risk of Torsades de pointes should be avoided from the start of study treatment through the end of Cycle 3
• Prophylactic administration of granulocyte colony-stimulating factor (G-CSF), filgrastim, pegfilgrastim, erythropoietin, or the transfusion of blood, red blood cells, or platelets within 14 days before the start of treatment and during Cycle 1. Chronic therapy with erythropoietin at stable dose that started at least 14 days before the first dose of DS-6157a may continue.
• Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, Grade ≤1. Participants with chronic Grade 2 toxicities may be eligible.
• Has spinal cord compression or clinically active central nervous system (CNS) metastases (including brain metastases), defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms
• Has known hypersensitivity to either the drug substances or inactive ingredients in the drug product
• Has a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety, efficacy, or any other assessments of the investigational regimen
• Has a documented history of myocardial infarction or unstable angina within 6 months before study treatment
• Has a medical history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or a serious cardiac arrhythmia requiring treatment
• Has a corrected QT by Fridericia's formula (QTcF), of \>470 ms based on the average of triplicate 12-lead electrocardiogram (ECG) per local read
• Has a documented history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Has clinically significant pulmonary compromise or requirement for supplemental oxygen
• Has clinically significant corneal disease
• Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
• Has active human immunodeficiency virus (HIV) infection as determined by plasma HIV RNA viral load.

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (5)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University of St. Louis

St Louis, Missouri, 63110, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

National Cancer Center Hospital East

Tokyo, 277-8577, Japan

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: February 14, 2020
• First Posted: February 19, 2020
• Study Start: May 8, 2020
• Primary Completion: March 11, 2022
• Study Completion: March 11, 2022
• Last Updated: February 15, 2024
• Results First Posted: February 15, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

JP (1); US (4)