Gastrointestinal Stromal TumorsPhase 1NCT04276415
DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumor (GIST)
A Phase 1 study testing DS-6157a in people with Gastrointestinal Stromal Tumors, run by Daiichi Sankyo at 5 sites in 2 countries.
Trial summary
This study will assess the safety, efficacy, and pharmacokinetics of DS-6157a in participants with advanced gastrointestinal stromal tumors (GIST). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumors
- What is being tested?
- DS-6157a
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 8 May 2020to 11 Mar 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- (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
- Hemoglobin ≥8.5 g/dL
- Absolute neutrophil count ≥1,500/mm^3
- Creatinine clearance ≥50 mL/min
- Aspartate aminotransferase ≤3 × upper limit of normal (ULN) (if liver metastases are present, ≤5 × ULN)
- Alanine aminotransferase ≤3 × ULN (if liver metastases are present, ≤5 × ULN)
- Total bilirubin ≤1.5 × ULN or ≤3.0 × ULN for participants with documented history of Gilbert's Syndrome
- Has an adequate treatment washout period prior to start of study treatment, defined as:
- Major surgery: ≥4 weeks (or 2 weeks for minor surgeries)
- Radiation therapy: ≥3 weeks (or 2 weeks for palliative radiation excluding pelvic radiation)
- Systemic anti-cancer therapy (except for anti-androgen for prostate cancer and bisphosphonate, denosumab, or medroxyprogesterone acetate for bone metastases):
- Cytotoxic chemotherapy: ≥3 weeks or 5 times the terminal elimination half-life (t½) of the chemotherapeutic agent, whichever is shorter
- Antibody and antibody-conjugates therapy: ≥3 weeks or 5 times the t½, whichever is longer
- Prior tyrosine kinase inhibitors (TKIs): washout period from 2 to 21 days depending on the TKI
- Immunotherapy: ≥4 weeks.
- Male participants with female partners of childbearing potential and female participants of child-bearing potential must agree to use a highly effective form of contraception, or avoid intercourse during and upon completion of the study and for at least 4 months (for males) and for at least 7 months (for females) after the last dose of study drug.
Who cannot join
- 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
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- 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.
- Has evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, as manifest by the detectable viral load (HBV-DNA or HCV-RNA, respectively)
- Is a lactating mother (women who are willing to temporarily interrupt breastfeeding will also be excluded), or pregnant as confirmed by pregnancy tests performed within 7 days before study treatment
- Women who plan to become pregnant while in the study and for at least 7 months after the last administration of study treatment
- Men who plan to father a child while in the study and for at least 4 months after the last administration of study treatment
- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, uncontrolled diabetes mellitus, active bleeding diatheses, substance abuse, or other medical condition that would increase the risk of toxicity or interfere with participation of the participant or evaluation of the clinical study
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
MD Anderson
Houston, Texas, 77030
Oregon Health and Science University
Portland, Oregon, 97239
Washington University of St. Louis
St Louis, Missouri, 63110
About this study
Official title: Phase 1, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Subjects With Advanced Gastrointestinal Stromal Tumor
This study will assess the safety, efficacy, and pharmacokinetics of DS-6157a in participants with advanced gastrointestinal stromal tumors (GIST).
Read the detailed description
This study is a two-part, multicenter, open-label, multiple-dose, first-in-human study of the antibody-drug conjugate (ADC) DS-6157a given as a single agent to participants with gastrointestinal stromal tumor (GIST).
This study will include 2 parts:
- Dose Escalation (Part 1)
- Dose Expansion (Part 2)
Dose Escalation: Participants with histopathologically documented advanced GIST not amenable to curative therapy may be included in which the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of DS-6157a monotherapy will be determined.
Dose Expansion: Once the RDE(s) is established for DS-6157a (Part 1), enrollment in Dose Expansion (Part 2) will commence in 2 cohorts. Participants with GIST who have progressed on or are intolerant to imatinib (IM) and at least one post-IM treatment will be enrolled in Cohort 1, and participants with GIST who progressed on IM and had not received a post-IM treatment (2nd line) will be enrolled in Cohort 2.
The study was terminated after Dose Escalation and the study never proceeded to the Dose Expansion part.
- Conditions
- Gastrointestinal Stromal Tumors
- Being tested
- DS-6157a
- Keywords
- Gastrointestinal stromal tumors, DS-6157a, Anti-drug antibody conjugate, G-protein coupled receptor 20 (GPR20)
- Medical subject headings
- Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DS-6157aDrug
Administered as a single agent intravenously (IV) every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: 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. Receives: Drug: DS-6157a |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
The plasma PK parameters were estimated using standard noncompartmental methods.
Measured: 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
The plasma PK parameters were estimated using standard noncompartmental methods.
Measured: 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
The plasma PK parameters were estimated using standard noncompartmental methods.
Measured: 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
The plasma PK parameters were estimated using standard noncompartmental methods.
Measured: 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
The plasma PK parameters were estimated using standard noncompartmental methods.
Measured: 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: Maximum Plasma Concentration (Cmax) for DS-6157a and Total Anti-GPR20 Antibody Following Intravenous Administration of DS-6157a
The plasma PK parameters were estimated using standard noncompartmental methods.
Measured: 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: Maximum Plasma Concentration (Cmax) for MAAA-1181a Following Intravenous Administration of DS-6157a
The plasma PK parameters were estimated using standard noncompartmental methods.
Measured: 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: Lowest Concentration Reached After a Single Dose (Ctrough) for DS-6157a and Total Anti-GPR20 Antibody Following Intravenous Administration of DS-6157a
The plasma PK parameters were estimated using standard noncompartmental methods.
Measured: 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: Lowest Concentration Reached After a Single Dose (Ctrough) for MAAA-1181a Following Intravenous Administration of DS-6157a
The plasma PK parameters were estimated using standard noncompartmental methods.
Measured: 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: Terminal Elimination Half-life (t1/2) for DS-6157a, Total Anti-GPR20 Antibody, and MAAA-1181a Following Intravenous Administration of DS-6157a
The plasma PK parameters were estimated using standard noncompartmental methods.
Measured: 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)
Best Overall Response Rate Following Intravenous Administration of DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumors (GIST) (Dose Escalation)
Based on Response Evaluation Criteria In Solid Tumors guidelines, complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions).
Measured: Baseline up to long-term follow up (defined as until the start of a new anti-cancer treatment, PD, death, lost to follow up, withdrawal of consent, or at the discretion of the Investigator, whichever occurs first), up to approximately 1 year 10 months.
Progression-free Survival (PFS) Following Intravenous Administration of DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumors (GIST) (Dose Escalation)
Progression-free survival (PFS) is defined as the time from randomization/start of study treatment to the date of event defined as the first documented radiological progression or death due to any cause.
Measured: Baseline up to the date of the first documented radiological progression or death due to any cause, whichever occurs first, up to approximately 1 year 10 months
Objective Response Rate (ORR) Following Intravenous Administration of DS-6157a in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) (Dose Escalation)
Measured: 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 Escalation)
Measured: 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 Escalation)
Measured: Baseline up to 5 years post-treatment
Number of Participants With Anti-drug Antibodies Against DS-6157a Following Intravenous Administration of DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumors (GIST)
Measured: Baseline up to 5 years post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2020
- Study start8 May 2020
- Primary completion11 Mar 2022
- Study completion11 Mar 2022
Why it stopped: The study was terminated due to a business decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gastrointestinal Stromal TumorsStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04276415
- Sponsor's protocol ID
- DS6157-A-U101
- Status last verified
- Feb 2024
- First submitted
- 14 Feb 2020
- Last updated
- 15 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Subjects With Advanced Gastrointestinal Stromal Tumor
- ClinicalTrials.gov ID
- NCT04276415
- Acronym / sponsor ID
- DS6157-A-U101
- Conditions
- Gastrointestinal Stromal Tumors
- Keywords
- Gastrointestinal stromal tumors, DS-6157a, Anti-drug antibody conjugate, G-protein coupled receptor 20 (GPR20)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to a business decision.
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- 8 May 2020 (actual)
- Primary completion
- 11 Mar 2022 (actual)
- Study completion
- 11 Mar 2022 (actual)
- First posted
- 19 Feb 2020 (actual)
- Results
- Posted 15 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the safety, efficacy, and pharmacokinetics of DS-6157a in participants with advanced gastrointestinal stromal tumors (GIST).
Detailed description
This study is a two-part, multicenter, open-label, multiple-dose, first-in-human study of the antibody-drug conjugate (ADC) DS-6157a given as a single agent to participants with gastrointestinal stromal tumor (GIST).
This study will include 2 parts:
- Dose Escalation (Part 1)
- Dose Expansion (Part 2)
Dose Escalation: Participants with histopathologically documented advanced GIST not amenable to curative therapy may be included in which the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of DS-6157a monotherapy will be determined.
Dose Expansion: Once the RDE(s) is established for DS-6157a (Part 1), enrollment in Dose Expansion (Part 2) will commence in 2 cohorts. Participants with GIST who have progressed on or are intolerant to imatinib (IM) and at least one post-IM treatment will be enrolled in Cohort 1, and participants with GIST who progressed on IM and had not received a post-IM treatment (2nd line) will be enrolled in Cohort 2.
The study was terminated after Dose Escalation and the study never proceeded to the Dose Expansion part.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation: DS-6157a | Experimental | Drug: DS-6157aParticipants with advanced gastrointestinal stromal tumor (GIST) who will receive an intravenous infusion of DS-6157a (escalating doses starting at 1.6 mg/kg). |
| Dose Expansion: Cohort 1 (3rd line or later) treated at RDE | Experimental | Drug: DS-6157aParticipants 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. |
| Dose Expansion: Cohort 2 (2nd line) treated at RDE | Experimental | Drug: DS-6157aParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- 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:
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DS-6157aAdministered as a single agent intravenously (IV) every 3 weeks | Drug | Dose Escalation: DS-6157a, Dose Expansion: Cohort 1 (3rd line or later) treated at RDE, Dose Expansion: Cohort 2 (2nd line) treated at RDE |
Primary outcome
Number of Participants With Dose-limiting Toxicities (DLT) Following Intravenous Administration of DS-6157a in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)
Time frame: Cycle 1 Day 1 to Day 21 (each cycle is 21 days)
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.
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)
Time frame: Baseline up to 30 days after end of treatment, up to approximately 1 year 10 months post-treatment
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.
Objective Response Rate (ORR) Following Intravenous Administration of DS-6157a in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) (Dose Expansion)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Baseline up to 5 years post-treatment
16 secondary outcomes
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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: Maximum Plasma Concentration (Cmax) for DS-6157a and Total Anti-GPR20 Antibody Following Intravenous Administration of DS-6157a
Time frame: 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: Maximum Plasma Concentration (Cmax) for MAAA-1181a Following Intravenous Administration of DS-6157a
Time frame: 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: Lowest Concentration Reached After a Single Dose (Ctrough) for DS-6157a and Total Anti-GPR20 Antibody Following Intravenous Administration of DS-6157a
Time frame: 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: Lowest Concentration Reached After a Single Dose (Ctrough) for MAAA-1181a Following Intravenous Administration of DS-6157a
Time frame: 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: Terminal Elimination Half-life (t1/2) for DS-6157a, Total Anti-GPR20 Antibody, and MAAA-1181a Following Intravenous Administration of DS-6157a
Time frame: 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)
Best Overall Response Rate Following Intravenous Administration of DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumors (GIST) (Dose Escalation)
Time frame: Baseline up to long-term follow up (defined as until the start of a new anti-cancer treatment, PD, death, lost to follow up, withdrawal of consent, or at the discretion of the Investigator, whichever occurs first), up to approximately 1 year 10 months.
Progression-free Survival (PFS) Following Intravenous Administration of DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumors (GIST) (Dose Escalation)
Time frame: Baseline up to the date of the first documented radiological progression or death due to any cause, whichever occurs first, up to approximately 1 year 10 months
Objective Response Rate (ORR) Following Intravenous Administration of DS-6157a in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) (Dose Escalation)
Time frame: 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 Escalation)
Time frame: 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 Escalation)
Time frame: Baseline up to 5 years post-treatment
Number of Participants With Anti-drug Antibodies Against DS-6157a Following Intravenous Administration of DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumors (GIST)
Time frame: Baseline up to 5 years post-treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Leader study director
Daiichi Sankyo
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DS-6157a in people with Gastrointestinal Stromal Tumors, run by Daiichi Sankyo at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 30 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-limiting Toxicities (DLT) Following Intravenous Administration of DS-6157a in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) (time frame: Cycle 1 Day 1 to Day 21 (each cycle is 21 days)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2024.