Study of XNW5004 Tablet in Combination With KEYTRUDA® (Pembrolizumab) in Subjects With Advanced Solid Tumors Who Failed Standard Treatments (KEYNOTE F19)
A Phase Ib/II Study of XNW5004 Tablet in Combination With KEYTRUDA® (Pembrolizumab) in Subjects With Advanced Solid Tumors Who Failed Standard Treatments (KEYNOTE F19)
3 other identifiers
interventional
204
1 country
1
Brief Summary
In this study, participants with different types of advanced solid tumors who failed standard treatments will be treated with XNW5004 in combination with KEYTRUDA® (pembrolizumab) .
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2023
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 17, 2023
CompletedFirst Posted
Study publicly available on registry
September 5, 2023
CompletedStudy Start
First participant enrolled
September 20, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 1, 2028
February 23, 2024
February 1, 2024
4.9 years
August 17, 2023
February 21, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Recommended Phase 2 Dose (RP2D) of XNW5004 in Combination With KEYTRUDA® (pembrolizumab) (Phase 1b Only)
Recommended Phase 2 dose (RP2D) of XNW5004 as administered orally twice daily (BID), continuously in 21-day cycles, in combination with KEYTRUDA® (pembrolizumab) in subjects with advanced solid tumors by safety data, pharmacokinetic data, pharmacodynamic data and efficacy data
The first 21-day cycle of therapy
Objective Response Rate (ORR) (Phase 2)
ORR is defined as the proportion of subjects who have a confirmed complete response (CR) or a partial response (PR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
Radiologic tumor assessments performed at baseline(within 28 days before start of study treatment)and every 9 weeks in the first 54 weeks (including the 54th week) after the first drug administration then every 12 weeks thereafter until confirmed disease
Secondary Outcomes (6)
ORR(Phase 1b)
Radiologic tumor assessments performed at baseline(within 28 days before start of study treatment)and every 9 weeks in the first 54 weeks (including the 54th week) after the first drug administration then every 12 weeks thereafter until confirmed disease
Duration of response (DOR)(Phase 1b and Phase 2)
Radiologic tumor assessments performed at baseline(within 28 days before start of study treatment)and every 9 weeks in the first 54 weeks (including the 54th week) after the first drug administration then every 12 weeks thereafter until confirmed disease
Progression free survival (PFS) (Phase 1b and Phase 2)
Radiologic tumor assessments performed at baseline(within 28 days before start of study treatment)and every 9 weeks in the first 54 weeks (including the 54th week) after the first drug administration then every 12 weeks thereafter until confirmed disease
Percentage of Participants With Adverse Events（AE） (Phase 2）
Up to 2.5 years
Maximum Concentration (Cmax) of XNW5004 in Solid Tumor Participants (Phase 1 and Phase 2）
Cycle 1 (each cycle is 21 days)
- +1 more secondary outcomes
Study Arms (7)
Dose escalation and Safety of XNW5004 in combination with KEYTRUDA® (pembrolizumab) (Phase Ib)
EXPERIMENTALDose escalation and safety with repeated administrations of XNW5004 in combination with infusions of KEYTRUDA® (pembrolizumab) in patients with advanced solid tumors.
HNSCC：XNW5004 in combination with KEYTRUDA® (pembrolizumab) (Phase II - cohort 1)
EXPERIMENTALRepeated administrations of XNW5004 in combination with infusions of KEYTRUDA® (pembrolizumab) in patients with head and neck squamous cell carcinoma (including nasopharyngeal carcinoma), urothelial carcinoma, metastatic castration-resistant prostate adenocarcinoma, small cell lung cancer, non-small cell lung cancer, other solid tumor (including cervical cancer)
Urothelial carcinoma：XNW5004 in combination with KEYTRUDA® (pembrolizumab) (Phase II - cohort 2)
EXPERIMENTALRepeated administrations of XNW5004 in combination with infusions of KEYTRUDA® (pembrolizumab) in patients with urothelial carcinoma
mCRPC：XNW5004 in combination with KEYTRUDA® (pembrolizumab) (Phase II - cohort 3)
EXPERIMENTALRepeated administrations of XNW5004 in combination with infusions of KEYTRUDA® (pembrolizumab) in patients with metastatic castration-resistant prostate adenocarcinoma
Small cell lung cancer：XNW5004 in combination with KEYTRUDA® (pembrolizumab) (Phase II - cohort 4)
EXPERIMENTALRepeated administrations of XNW5004 in combination with infusions of KEYTRUDA® (pembrolizumab) in patients with small cell lung cancer
non-small cell lung cancer:XNW5004 in combination with KEYTRUDA®(pembrolizumab)(PhaseII-cohort5)
EXPERIMENTALRepeated administrations of XNW5004 in combination with infusions of KEYTRUDA®(pembrolizumab) in patients with non-small cell long cancer
：XNW5004 in combination with KEYTRUDA® (pembrolizumab) (Phase II - cohort 6)
EXPERIMENTALRepeated administrations of XNW5004 in combination with infusions of KEYTRUDA® (pembrolizumab) in patients with other solid tumor (including cervical cancer)
Interventions
XNW5004 an EZH2 inhibitor, BID, administered in continuous
KEYTRUDA® (pembrolizumab) a programmed death receptor (PD-1) blocking antibody administered at 200mg by intravenous (IV) infusions every 3 weeks.
Eligibility Criteria
You may qualify if:
- Sign informed consent form prior to the commencement of any research activity/procedure.
- Age ≥ 18.
- Cohort 3 (mCRPC cohort) is male-only, and no gender restrictions for other cohorts.
- Subjects with advanced solid tumors who meet one of the following requirements can be enrolled in the study. No cohorts planned for the Phase Ib study, whereas the Phase II study is divided into 6 cohorts:
- Cohort: 1 Histologically or cytologically confirmed recurrent or metastatic head and neck squamous cell carcinoma (including nasopharyngeal carcinoma),has progressed after treatment with a standard regimen containing PD-1/PD-L1 inhibitors.
- Cohort 2: Histologically confirmed advanced urothelial carcinoma (including urothelial carcinoma of bladder, renal pelvis, ureter, and urethral origin) that is not suitable for surgical treatment and has progressed after treatment with a standard regimen containing PD-1/PD-L1 inhibitors.
- Cohort 3:
- Metastatic castration-resistant prostate adenocarcinoma with histological or cytological evidence of disease progression except neuroendocrine or small cell carcinoma; Imaging examination (CT/MRI/ bone scan) confirmed metastatic lesions.
- Failed previous standard treatments, and at least received one second-generation anti-androgen drug treatment (including but not limited to abiraterone acetate, enzalutamide or apalutamide).
- Disease progression at screening.
- Continuous luteinizing hormone-releasing agonist (LHRHa) or antagonist therapy (drug castration) or prior bilateral orchiectomy (surgical castration).
- Testosterone at screening was at castration level.
- Cohort 4: Subjects with histologically or cytologically confirmed extensive-stage small cell lung cancer with disease progression after first-line standard therapy.
- Cohort 5: Subjects with histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer.
- Cohort 5a: Previous use of and resistant to EGFR inhibitors and failed standard treatment.
- +11 more criteria
You may not qualify if:
- Cohort 1 (head and neck squamous cell carcinoma cohort)
- Neuroendocrine carcinoma and small cell carcinoma.
- Cohort 3 (mCRPC)
- Severe bone injury caused by tumor bone metastasis, including severe, uncontrolled bone pain as judged by the investigator, bone fractures or spinal cord compression at critical parts of the body that occurred in the last 6 months or are expected to occur in a near future.
- Any previous treatment targeting T-cell co-stimulation or checkpoint pathways.
- Cohort 5 (non-small cell lung cancer)
- Any previous treatment targeting T-cell co-stimulation or checkpoint pathways other than PD-1 / PD-L1 inhibitors.
- Combined with other targetable driver mutations either alone or in addition to EGFR, including but not limited to: ALK gene rearrangement, ROS1 mutations, BRAFV600E mutation, etc. (For cohort 5a only.)
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher irAE.
- Prior exposure to EZH2 inhibitor(s) or EZH1/2 inhibitor(s) (including but not limited to tazemetostat).
- Subjects known to be allergic to the study drug or its active ingredients or excipients, or subjects with prior severe hypersensitivity to other monoclonal antibody therapy in the past.
- Subjects who received anti-tumor therapies including chemotherapy, immunotherapy, radical radiotherapy, major surgery, targeting therapy and other anti-tumor therapies within 4 weeks or 5 half-lives of the drug (whichever is shorter) before the first dose; or received palliative radiotherapy within 2 weeks before the first dose.
- Subjects who participated in any other clinical trial of anti-tumor therapy within 28 days before the first dosing, and the last dose of other anti-tumor trial drug is within 28 days prior to the first administration of study drug in this trial.
- Subjects who underwent major surgery within 4 weeks prior to the start of the study treatment, or who are scheduled to undergo a major surgery during the study period (procedures such as puncture or lymph node biopsy is allowed).
- Subjects who have an allogenic bone marrow transplantation or solid organ transplantation.
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Evopoint Biosciences Inc.lead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (1)
Sun Yat-sen University Cancer Center (SYSUCC)
Guangzhou, Guodong Province, 528404, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Li Zhang, M.D.
botanic physician
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 17, 2023
First Posted
September 5, 2023
Study Start
September 20, 2023
Primary Completion (Estimated)
August 1, 2028
Study Completion (Estimated)
August 1, 2028
Last Updated
February 23, 2024
Record last verified: 2024-02
Data Sharing
- IPD Sharing
- Will not share