Carcinoma, Cervical Cancer, Non-small Cell Lung Cancer, Other Solid Tumors, Prostate Cancer, Small-cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck, Urothelial Carcinoma
Conditions
Keywords
XNW5004, EZH2 inhibitor, KEYTRUDA® (pembrolizumab), immune checkpoint inhibitors
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) .
Interventions
DRUGXNW5004
XNW5004 an EZH2 inhibitor, BID, administered in continuous
DRUGKEYTRUDA® (pembrolizumab) 25 mg/mL Solution for Injection
KEYTRUDA® (pembrolizumab) a programmed death receptor (PD-1) blocking antibody administered at 200mg by intravenous (IV) infusions every 3 weeks.
Sponsors
Evopoint Biosciences Inc.
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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: 1. 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. 2. 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). 3. Disease progression at screening. 4. Continuous luteinizing hormone-releasing agonist (LHRHa) or antagonist therapy (drug castration) or prior bilateral orchiectomy (surgical castration). 5. 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. 1. Cohort 5a: Previous use of and resistant to EGFR inhibitors and failed standard treatment. 2. Cohort 5b: No driver gene mutations identified and failed standard therapy containing PD-1/PD-L1 inhibitors. * Cohort 6: Subjects with advanced solid tumors other than those described in the above cohorts, and failed standard therapy. For recurrent or metastatic cervical cancer, it should be histologically or cytologically confirmed as squamous cell carcinoma, progressed after systematic standard treatment, and is not suitable for radical therapy . * For patients who have progressed on treatment with PD-1/PD-L1 inhibitors administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies, PD-1/PD-L1 inhibitor treatment progression is defined by meeting all of the following criteria: 1. Has received at least 2 doses of approved PD-1/PD-L1 inhibitors. 2. Documented objective radiographic progression following initiation of treatment with a PD-1/PD-L1 inhibitor. Subjects should not be enrolled if they are suspected of permanent withdrawal due to pseudo-progression after previous PD-1/PD-L1 inhibitor treatment. * To the extent possible, provide formalin-fixed, paraffin-embedded (FFPE) tumor tissue section (previously archived or fresh) samples and blood samples that meet the detection requirements for exploratory studies. * Life expectancy ≥ 3 months. * At least one measurable lesion according to RECIST 1.1 criteria. * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. * Have adequate organ function. * Females of child-bearing potential and males who use adequate birth control through 6 months post last dose.
Exclusion criteria
* Cohort-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 Dose (RP2D) of XNW5004 in Combination With KEYTRUDA® (pembrolizumab) (Phase 1b Only) | The first 21-day cycle of therapy | 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 |
| Objective Response Rate (ORR) (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 | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | ORR is defined as the proportion of subjects who have a confirmed CR or a PR per RECIST 1.1. |
| 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 | DOR is defined defined as the length of time from the date of first confirmed CR or PR per RECIST 1.1(whichever status is recorded first) to the date of first evaluation of progressive disease, or death due to any reasons. |
| 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 | PFS is defined as the the length of time from the date of first administration of the study drug until the date of disease progression or death. |
| Percentage of Participants With Adverse Events（AE） (Phase 2） | Up to 2.5 years | An AE is any untoward medical occurrence in a clinical investigation subject administered a study drug and an AE can therefore be any symptom, disease or an abnormal laboratory finding, whether or not related to the investigational product. Severity of AEs is assessed according to Common Terminology Criteria for Adverse Events Version (CTCAE 5.0). |
| Maximum Concentration (Cmax) of XNW5004 in Solid Tumor Participants (Phase 1 and Phase 2） | Cycle 1 (each cycle is 21 days) | Blood samples were collected at specified intervals for the determination of Cmax. |
| the area under the plasma concentration-time curve at steady state (AUCss) in Solid Tumor Participants (Phase 1 and Phase 2） | Cycle 1 (each cycle is 21 days) | Blood samples were collected at specified intervals for the determination of AUCss. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORLi Zhang, M.D.
botanic physician
Outcome results
None listed