A Study of DS-9606a in Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
This study will assess the safety and tolerability of DS-9606a in patients with advanced solid tumors.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
Detailed Description
This first-in-human, phase 1 study will consist of 2 parts. In Part A (Dose Escalation), the primary objectives will be to investigate the safety and tolerability of DS-9606a in advanced solid tumors and to determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE). In Part B (Dose Expansion), the safety and tolerability of DS-9606a will be further explored and the overall response rate will be assessed.
The secondary objectives of the study will assess pharmacokinetic properties of DS-9606a and investigate the duration of response and progression-free survival of DS-9606a, and assess the immunogenicity of DS-9606a.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Dose Escalation: DS-9606a Participants who will receive an intravenous (IV) dose of DS9606a starting at 0.016 mg/kg every 3 weeks. |
Drug: DS-9606a
Intravenous infusion
|
Experimental: Dose Expansion: Cohort B-1 Participants with ovarian cancer who will receive an intravenous (IV) dose of DS9606a at the recommended dose for expansion (RDE) every 3 weeks. |
Drug: DS-9606a
Intravenous infusion
|
Experimental: Dose Expansion: Cohort B-2 Participants with refractory germ cell tumors who will receive an intravenous (IV) dose of DS9606a at the recommended dose for expansion (RDE) every 3 weeks. |
Drug: DS-9606a
Intravenous infusion
|
Outcome Measures
Primary Outcome Measures
- Number of Participants with Dose-Limiting Toxicities (DLT) in Participants Receiving DS-9606a [Cycle 1 Day 1 through Day 21 of Cycle 2 (each cycle is 21 days)]
- Number of Participants with Treatment-emergent Adverse Events (TEAEs) in Participants Receiving DS-9606a [Cycle 1 Day 1 to 30 days after last dose, up to 36 months (each cycle is 21 days)]
- Overall Response Rate of DS-9606a as Assessed by the Investigator in Participants Receiving DS-9606a (Dose Expansion) [Cycle 1 Day 1 and then every 6 weeks for 24 weeks, and then every 12 weeks, up to 36 months (each cycle is 21 days)]
Secondary Outcome Measures
- Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) [Cycles 1-3, Day 1:pre-dose, end of flush, 4 hours (hr) and 8 hrs post-dose (Cycles 1 and 3 only); Cycle 1 and 3,Day 2; Cycle 1 and 3,Days 4,8, and 15; Cycle 2,Days 8 and 15; Cycle 4,Day 1 and pre-dose every cycle, up to 36 months (each cycle is 21 days)]
- Pharmacokinetic Parameter Maximum Concentration (Cmax) [Cycles 1-3, Day 1:pre-dose, end of flush, 4 hours (hr) and 8 hrs post-dose (Cycles 1 and 3 only); Cycle 1 and 3,Day 2; Cycle 1 and 3,Days 4,8, and 15; Cycle 2,Days 8 and 15; Cycle 4,Day 1 and pre-dose every cycle, up to 36 months (each cycle is 21 days)]
- Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) [Cycles 1-3, Day 1:pre-dose, end of flush, 4 hours (hr) and 8 hrs post-dose (Cycles 1 and 3 only); Cycle 1 and 3,Day 2; Cycle 1 and 3,Days 4,8, and 15; Cycle 2,Days 8 and 15; Cycle 4,Day 1 and pre-dose every cycle, up to 36 months (each cycle is 21 days)]
- Pharmacokinetic Parameter Trough Concentration (Ctrough) [Cycles 1-3, Day 1:pre-dose, end of flush, 4 hours (hr) and 8 hrs post-dose (Cycles 1 and 3 only); Cycle 1 and 3,Day 2; Cycle 1 and 3,Days 4,8, and 15; Cycle 2,Days 8 and 15; Cycle 4,Day 1 and pre-dose every cycle, up to 36 months (each cycle is 21 days)]
- Duration of Response (DoR) as Assessed by the Investigator in Participants Receiving DS-9606a [Cycle 1 Day 1 and then every 6 weeks for 24 weeks, and then every 12 weeks, up to 36 months (each cycle is 21 days)]
- Disease Control Rate (DCR) as Assessed by the Investigator in Participants Receiving DS-9606a [Cycle 1 Day 1 and then every 6 weeks for 24 weeks, and then every 12 weeks, up to 36 months (each cycle is 21 days)]
- Time to Response (TTR) as Assessed by the Investigator in Participants Receiving DS-9606a [Cycle 1 Day 1 and then every 6 weeks for 24 weeks, and then every 12 weeks, up to 36 months (each cycle is 21 days)]
- Progression-free Survival (PFS) as Assessed by the Investigator in Participants Receiving DS-9606a [Cycle 1 Day 1 and then every 6 weeks for 24 weeks, and then every 12 weeks, up to 36 months (each cycle is 21 days)]
- Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Percentage of Participants Who Have Treatment-emergent ADA [Cycle 1 Days 1 and 15, Cycles 2 and 3 Day 1, Cycle 4 Day 1 and all cycles thereafter on Day 1, up to 36 months (each cycle is 21 days)]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
At least 18 years old at the time of written informed consent
-
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
-
Availability of archived tumor tissue samples (mandatory); patients with germ cell tumors without archived tumor samples may be allowed with approval
-
Has a left ventricular ejection fraction (LVEF) ≥50% as determined by either an echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 28 days before the start of study treatment
-
Adequate bone marrow and organ function within 7 days before the start of study treatment
-
Life expectancy ≥3 months
-
Adequate treatment washout period prior to start of study treatment
-
Male patients with female partners of childbearing potential and female patients of child-bearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study for at least 4 months (for males) and for at least 7 months (for females) after the last dose of study drug. Males must agree not to freeze or donate sperm throughout the study period for at least 4 months after final administration of study drug. Females must agree not to donate or retrieve ova for own use throughout the study period and for at least 7 months after final study drug administration.
Dose Escalation Participants Only:
-
Histologically- or cytologically-documented locally advanced or metastatic cancers, including but not limited to: ovarian cancer (including fallopian tube and primary peritoneal carcinoma), germ cell tumors, uterine and endometrial cancers, pancreatic adenocarcinoma, non-squamous NSCLC, or gastric cancer
-
Disease progression with standard of care therapies for metastatic disease known to confer benefit, or are intolerant to or refuse standard treatment.
Dose Expansion Participants Only:
-
Consent to provide pre-treatment (mandatory) and on-treatment tissue biopsy sample (mandatory if not clinically contraindicated)
-
Histologically or cytologically-documented locally advanced or metastatic cancers including:
-
Cohort B-1: Ovarian cancer
-
Cohort B-2: Refractory germ cell tumors
Exclusion Criteria:
-
Has history or current presence of central nervous system metastases, except for participants who have completed radiotherapy or surgery ≥4 weeks before the start of treatment, and fulfill all criteria (no evidence of disease progression in the CNS and no requirement for chronic corticosteroids) within 2 weeks before the start of treatment
-
Other invasive malignancy within 2 years; prior or concurrent non-invasive malignancies and/or patients with localized malignancies that were treated with curative intent who remain disease-free and are considered low likelihood for recurrence may be enrolled
-
History of myocardial infarction or unstable angina within 6 months before study treatment
-
Has a history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or a serious cardiac arrhythmia requiring treatment
-
Has a corrected QT interval by Fridericia's formula (QTcF), of >470 ms based on the average of triplicate 12-lead electrocardiogram (ECG) per local read
-
Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
-
Has an uncontrolled infection requiring ongoing or long-term therapy
-
Has a known active hepatitis or uncontrolled hepatitis B or C infection
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Florida Cancer Specialists & Research Institute, LLC | Sarasota | Florida | United States | 33916 |
2 | Tennessee Oncology, PLLC | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- Daiichi Sankyo, Inc.
Investigators
- Study Director: Clinical Director, Daiichi Sankyo, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DS9606-137
- 2022-000120-38
- REFMAL 823