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

Daiichi Sankyo

Status and phase: Enrolling; Phase 1

Conditions: Metastatic Cancer; Advanced Cancer; Germ Cell Tumor; Ovarian Cancer

Treatments: Drug: DS-9606a

Study type: Interventional

Funder types: Industry

Identifiers

NCT05394675

2022-000120-38 (EudraCT Number)

DS9606-137

REFMAL 823 (Other Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment: 85 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 in Part A); 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 6 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 6 months after final administration of study drug. Investigators will advise male patients on the conservation of sperm prior to study treatment. 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 tumor screening and to provide an archived tumor sample if available, or a newly obtained pre-treatment tumor biopsy and consent to provide pre-treatment biopsy sample and on-treatment tissue biopsy sample (mandatory if not clinically contraindicated)
• Histologically or cytologically-documented locally advanced or metastatic ovarian cancer

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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85 participants in 2 patient groups

Dose Escalation: DS-9606a

Experimental group

Description:

Participants who will receive an intravenous (IV) dose of DS9606a starting at 0.016 mg/kg every 3 weeks.

Treatment:

Drug: DS-9606a

Dose Expansion: DS-9606a

Experimental group

Description:

Participants with ovarian cancer who will receive an intravenous (IV) dose of DS9606a at the recommended dose for expansion (RDE) every 3 weeks.

Treatment:

Drug: DS-9606a