A Study Evaluating DS-1055a in Participants With Relapsed or Refractory Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of DS-1055a in participants with relapsed or refractory locally advanced or metastatic solid tumors for which no standard treatment is available.

Detailed Description
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This Phase 1, open-label, non-randomized, dose escalation, first-in-human study will assess the safety and tolerability of DS-1055a, determine the maximum tolerated dose of DS-1055a, pharmacokinetic (PK) properties of DS-1055a, and the incidence of anti-drug antibodies (ADAs) against DS-1055a and other antibodies.

Official Title
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A Phase 1, First In Human Study of DS-1055a in Subjects With Relapsed or Refractory Locally Advanced or Metastatic Solid Tumors

Conditions
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Solid Tumor, Advanced Cancer, Metastatic Solid Tumor

Intervention / Treatment
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* Drug: DS-1055a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a histopathologically documented locally advanced or metastatic head and neck, gastric, esophageal cancer, non-small cell lung cancer, or melanoma. Participants with other types of solid tumors may be eligible following discussion with the Sponsor. Has a relapsed or refractory disease that is not amenable to curative standard therapy. Is 18 years of age or older. Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1, with no deterioration for two weeks. Has a measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Has adequate organ function within 7 days before enrollment. Is able to provide written informed consent and is willing and able to comply with the protocol. Exclusion Criteria: Has a concurrently active second malignancy, other than adequately treated non-melanoma skin cancers, in situ melanoma or in situ cervical cancer. Participants with history of the second malignancy have been disease-free for <3 years. Has a history of (non-infectious) interstitial lung disease (ILD) that required steroids, currently has ILD, or when suspected ILD cannot be ruled out by imaging at screening. Has a history of severe pulmonary compromise or requirement of supplemental oxygen within 6 months before enrollment. Has active hepatitis B or hepatitis C virus infection. Has received prior immunotherapy with a Grade 3 or higher, or any unresolved ≥Grade 2 immune-related adverse event.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation (DS-1055a)<br>Participants will be enrolled into groups with each group receiving an increased dose from the previous group as safety assessments permit in order to determine the optimal dose for safety and tolerability. | Drug: DS-1055a<br>* Administered as an intravenous infusion on Day 1 of every 21-day cycle following low dose administration(s) in priming dose period. Infusion duration: 180 minutes for the first infusion, and if no infusion-related reaction, 120 minutes for subsequent infusions<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 | A dose-limiting toxicity (DLT) is defined as any treatment-emergent adverse event (TEAE) that occurs during the DLT evaluation period (21 days), excluding toxicities clearly related to disease progression or intercurrent illness or to concomitant medications or to concomitant procedures and is Grade 3 or above according to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0, with certain specified exceptions. | 21 days of Cycle 1 | 
| Number of participants with adverse events | Adverse events were assessed using National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0. | Baseline up to approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) |  | Priming Dose Cycle 1 Day 1 to Cycle 4 Day 1, and every 2 cycles from Cycle 4 to end of treatment, within approximately 2 years (each cycle is 21 days) | 
| Time to Reach Maximum Plasma Concentration (Tmax) |  | Priming Dose Cycle 1 Day 1 to Cycle 4 Day 1, and every 2 cycles from Cycle 4 to end of treatment, within approximately 2 years (each cycle is 21 days) | 
| Area Under the Plasma Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) |  | Priming Dose Cycle 1 Day 1 to Cycle 4 Day 1, and every 2 cycles from Cycle 4 to end of treatment, within approximately 2 years (each cycle is 21 days) | 
| Minimum Observed Concentration (Ctrough) |  | Priming Dose Cycle 1 Day 1 to Cycle 4 Day 1, and every 2 cycles from Cycle 4 to end of treatment, within approximately 2 years (each cycle is 21 days) | 
| The Incidence of Anti-Drug Antibodies (ADA) and Other Antibodies |  | From pre-treatment to follow-up visit (within approximately 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumor, Advanced Cancer, Metastatic Solid Tumor, DS-1055a