A Study of DS-9606a in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study will assess the safety and tolerability of DS-9606a in patients with advanced solid tumors.

Detailed Description
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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.

Official Title
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A Phase 1, First-in-Human Study of DS-9606a in Patients With Tumor Types Known to Express Claudin-6 (CLDN6)

Conditions
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Germ Cell Tumor, Advanced Cancer, Metastatic Cancer, Ovarian Cancer

Intervention / Treatment
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* Drug: DS-9606a


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Dose escalation and dose expansion study model
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation: DS-9606a<br>Participants who will receive an intravenous (IV) dose of DS9606a starting at 0.016 mg/kg every 3 weeks. | Drug: DS-9606a<br>* Intravenous infusion<br>|
| Experimental: Dose Expansion: Cohort B-1<br>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<br>* Intravenous infusion<br>|
| Experimental: Dose Expansion: Cohort B-2<br>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<br>* Intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Cancer, Metastatic Cancer, Ovarian Cancer, Germ Cell Tumor, DS-9606a