A Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid Tumors

Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorDaiichi Sankyo

About this trial

This study will evaluate the safety, tolerability, and efficacy of valemetostat tosylate in combination with DXd ADC in patients with advanced solid tumors.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

At least 18 years or the minimum legal adult age (whichever is greater) at the time the ICF is signed.

Has at least 1 measurable lesion based on investigator imaging assessment (computed tomography or magnetic resonance imaging) using RECIST v 1.1 at Screening.

Is willing to provide an adequate tumor sample.

Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening.

Disqualifiers

Has previously been treated with any enhancer of zeste homolog inhibitors.

Uncontrolled or significant cardiovascular disease.

Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.

Has leptomeningeal carcinomatosis or metastasis.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Valemetostat tosylate

    Drug

    Administered orally once daily

  • T-DXd

    Drug

    One IV infusion Q3W on Day 1 of each 21-day cycle

  • Dato-DXd

    Drug

    One IV infusion Q3W on Day 1 of each 21-day cycle.

Treatment groups

210 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Part 1: Dose Escalation Phase (Sub-protocol B)Experimental treatment 2 interventions
Group B: Part 1: Dose Escalation Phase (Sub-protocol C)Experimental treatment 2 interventions
Group C: Part 1: Dose Escalation (Sub-protocol A)Experimental treatment 2 interventions
Group D: Part 2: Dose Expansion (Sub-protocol B)Experimental treatment 2 interventions
Group E: Part 2: Dose Expansion (Sub-protocol C)Experimental treatment 2 interventions
Group F: Part 2: Dose Expansion (Sub-protocol A)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Number of Participants Reporting Dose-limiting Toxicities (Part 1 Dose Escalation)

Time frame
Cycle 1 Day 1 up to Day 21 (each cycle is 21 days)
2

Number of Participants Reporting Treatment-emergent Adverse Events (Part 1 Dose Escalation)

Time frame
Screening up to 40 days after last dose
3

Objective Response Rate Based on Investigator Assessment (Part 2 Dose Expansion)

Objective response rate (ORR) is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v 1.1 criteria. CR is defined as a disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions.

Time frame
Baseline (Screening), at every 6 weeks from Cycle 1 Day 1 in the first year, and every 12 weeks thereafter until disease progression or until the start of a new anticancer treatment, up to approximately 5 years

Secondary outcomes

1

Overall Survival

Time frame
Date of enrollment up to date of death due to any cause, up to approximately 5 years
2

Progression-free Survival

Disease progression will be determined by investigator assessment of tumor scans and using RECIST v 1.1 criteria.

Time frame
Date of enrollment up to date of radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 5 years
3

Duration of Response (DoR)

CR is defined as a disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions.

Time frame
Date of first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the first documentation of objective tumor progression or to death due to any cause (whichever occurs first), up to approximately 5 years
4

Objective Response Rate Based on Investigator Assessment (Part 1 Dose Escalation)

Objective response rate (ORR) is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v 1.1 criteria. CR is defined as a disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions.

Time frame
Baseline (Screening), at every 6 weeks from Cycle 1 Day 1 in the first year, and every 12 weeks thereafter until disease progression or until the start of a new anticancer treatment, up to approximately 5 years

Other outcomes

Sponsors and contacts

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