CLINICAL TRIAL / NCT06244485
A Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid Tumors
- Interventional
- Recruiting
- NCT06244485
Contact Information
A Phase 1b, Multicenter, Open-Label Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid Tumors
This study will evaluate the safety, tolerability, and efficacy of valemetostat tosylate in combination with DXd ADC in patients with advanced solid tumors.
This is a 2-part study of valemetostat in combination with DXd ADCs in patients with
HER2-positive gastric cancer, non-squamous NSCLC, or unresectable or metastatic HER2 low
breast cancer. The study will begin with a Part 1 Dose-escalation Phase and will continue
until the recommended dose for expansion "RDE" of valemetostat is determined and will
then be followed by a Part 2 Dose-expansion Phase to further evaluate the safety and
tolerability of the combination.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Key Inclusion Criteria
All participants must meet all of the following criteria, as well as all criteria from
the relevant sub-protocol to be eligible for enrollment:
- 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.
Additional Key Inclusion for Sub-Protocol A:
- Diagnosed with pathologically documented breast cancer that:
1. Is unresectable or metastatic.
2. Has progressed on and would no longer benefit from endocrine therapy in hormone
receptor-positive subjects in the opinion of the investigator.
3. Has been treated with at least 1 and at most 2 prior lines of chemotherapy in
the recurrent or metastatic setting.
4. Has a history of low HER2 expression, defined as IHC 2+ /ISH-negative or IHC 1+
(ISH-negative or untested). ), as classified by the American Society of
Clinical Oncology/College of American Pathologists 2018 HER2 testing
guidelines.
5. Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology
testing (per American Society of Clinical Oncology/College of American
Pathologists guidelines
Additional Key Inclusion for Sub-Protocol B:
• Gastric or GEJ adenocarcinoma that is (a) unresectable or metastatic or (b)
has progressed on trastuzumab or approved trastuzumab biosimilar-containing
regimen.
Additional Key Inclusion for Sub-Protocol C:
- Pathologically documented Stage IIIB, IIIC, or IV non-squamous NSCLC with or without
AGA at the time of enrollment.
- Must meet prior therapy requirements:
- Participants without AGA: (a) received platinum-based chemotherapy in
combination with α-PD-1/α -PD-L1 mAb as a prior line of therapy or (b) received
platinum-based chemotherapy and α -PD-1/ α -PD-L1 mAb (in either order)
sequentially as 2 prior lines of therapy.
- Participants with AGA: (a) has been treated with at least 1 or 2 prior lines of
applicable targeted therapy that is locally approved for participant's genomic
alteration at the time of Screening, (b) participants who have received
platinum-based chemotherapy as a prior line of cytotoxic therapy, (c) may have
received α -PD-1/α -PD-L1 mAb alone or in combination with a cytotoxic agent
Key Exclusion Criteria
- 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.
- Clinically severe pulmonary compromise resulting from intercurrent pulmonary
illnesses.
- Current use of moderate or strong cytochrome P450 (CYP)3A inducers.
- Systemic treatment with corticosteroids (>10 mg daily prednisone equivalents).
- History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
- Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection
requiring treatment with intravenous (IV) antibiotics, antivirals, or antifungals.
- Female who is pregnant or breastfeeding or intends to become pregnant during the
study.
- Psychological, social, familial, or geographical factors that would prevent regular
follow-up.
Additional Key Exclusion for Sub-Protocol A:
- Has previously received any anti-HER2 therapy in the metastatic setting.
- Has received prior treatment with an antibody-drug conjugate that consists of an
exatecan derivative that is a topoisomerase I inhibitor, including either as part of
prior treatment history or within prior participation in a clinical study.
Additional Key Exclusion for Sub-Protocol B:
* Participants who have received an antibody-drug conjugate consisting of an exatecan
derivative that is a topoisomerase I inhibitor.
Additional Key Exclusion for Sub-Protocol C:
* Has received any agent, including an ADC, containing a chemotherapeutic agent targeting
topoisomerase I or TROP2-targeted therapy including Dato-DXD
- Solid Tumors