A Single-arm, Open-label, Multicenter, Phase Ib/II Clinical Trial of CVL237 Tablets in Combination With Serplulimab Injection for the Treatment of Advanced Solid Tumors With PTEN Loss or Low Expression

This is a single-arm, open-label, multicenter, Phase Ib/II clinical trial of CVL237 tablets in combination with serplulimab injection for the treatment of advanced solid tumors with PTEN loss or low expression

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced or Metastatic Solid Tumors; PTEN Loss or Low Expression
• Intervention / Treatment: Drug: CVL237 tablets

Detailed Description

A single-arm, open-label, multicenter, Phase Ib/II clinical trial of CVL237 tablets in combination with serplulimab injection for the treatment of advanced solid tumors with PTEN loss or low expression

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18 to 75 years (inclusive of both endpoints), regardless of gender；
2. Patients with locally advanced or metastatic solid tumors (gastric cancer, endometrial cancer, cervical cancer, ovarian cancer, lung cancer, breast cancer, and other tumor types) confirmed by histology or cytology, and with PTEN loss or low expression. Patients who have experienced disease progression after standard treatment or have intolerable toxicities from prior therapies, or for whom no standard treatment is available, as determined by the investigator. For breast cancer participants, PTEN low expression is limited to those who have relapsed or metastasized after prior treatment with trastuzumab and/or CDK4/6 inhibitors;
3. PTEN loss or low expression confirmed by IHC staining. The definition of PTEN loss or low expression is referenced as follows: Using a dual-scoring method, score the percentage of positive cells: 0% = 0 points; 1-25% = 1 point; 26-50% = 2 points; 51-75% = 3 points; ≥76% = 4 points. Score the staining intensity: no staining = 0 points; light brownish-yellow = 1 point; brownish-yellow = 2 points; brown = 3 points. Add the scores from the two categories. A total score of 0-2 is classified as "A," 3-6 as "B," and ≥7 as "C." "A" indicates negative expression and is defined as PTEN loss; "B" indicates PTEN positive with low expression; "C" indicates PTEN positive with high expression;
4. ECOG Performance Status (PS) of 0-1;
5. Life expectancy of ≥3 months;
6. Presence of at least one measurable lesion according to RECIST v1.1 criteria;
7. Sufficient bone marrow and organ function levels (no use of blood products and/or hematopoietic growth factors within 14 days prior to the start of study treatment):
8. Fertile eligible study participants (both male and female) must agree to use a reliable method of contraception (hormonal or barrier methods or abstinence, etc.) with their partner during the trial and for at least 6 months after the last dose of study drug; Women of childbearing potential must not breastfeed. Women of childbearing potential must also have a negative pregnancy test prior to the first dose of study drug;
9. Voluntarily participating in this clinical trial, understanding the study procedures, and being able to provide written informed consent.

Exclusion Criteria:

1. Surgery or Trauma: Undergone major organ surgery or experienced significant trauma within 4 weeks before the first administration of the study drug, or requires elective surgery during the trial period; undergone core needle biopsy or other minor surgeries (excluding central venous catheterization or port-a-cath implantation) within 7 days before the first dose;
2. Insufficient Washout Period for Prior Anti-tumor Treatments;
3. Inability to Swallow, Chronic Diarrhea, or Bowel Obstruction: Presence of factors that may affect the intake and absorption of the study drug;
4. Unhealed Wounds or Interventions: Unhealed wounds, abdominal fistulas, gastrointestinal stent placement, or extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months before the first dose;
5. Uncontrolled Effusions: Presence of uncontrolled pleural effusion, ascites, or pericardial effusion;
6. Concurrent Use of Certain Medications: Currently using medications that are substrates of OATP1B1 and OATP1B3, CYP3A4/5 substrates, moderate or strong CYP3A4/5 inhibitors, or strong CYP3A4/5 inducers, and cannot discontinue or switch to alternative treatments before starting the study treatment;
7. Central Nervous System (CNS) Metastases or Meningitis: Participants with untreated or active CNS metastases (e.g., brain edema, requiring steroid intervention, or progressive brain metastases) and/or carcinomatous meningitis. However, participants with CNS metastases who have received adequate local treatment (surgery or radiotherapy) and have no progression on imaging at screening after completion of local treatment may be eligible. Participants must have stable neurological symptoms for at least 2 weeks before the first dose and not require corticosteroid treatment;
8. History of Severe Allergic Reactions: Known history of severe allergic reactions to multiple medications;
9. Immune-related Adverse Events (irAEs): Participants who experienced ≥ Grade 3 irAEs or ≥ Grade 2 immune-related myocarditis during prior immunotherapy are not eligible;
10. Active or Potentially Recurrent Autoimmune Diseases: Participants with any active or history of autoimmune diseases that may recur (e.g., systemic lupus erythematosus, rheumatoid arthritis, vasculitis), except for clinically stable autoimmune thyroid disease or Type I diabetes;
11. Systemic Corticosteroid or Immunosuppressive Therapy: Participants who received systemic corticosteroids (prednisone > 10 mg/day or equivalent) or other immunosuppressive agents within 14 days before the first dose of study drug. Exceptions include: Use of topical, ocular, intra-articular, nasal, or inhaled corticosteroids; Short-term (≤7 days) use of corticosteroids (≤10 mg prednisone equivalent) for prophylaxis or treatment of non-autoimmune allergic conditions (e.g., preventing contrast agent allergy);
12. Interstitial Pneumonia or Severe Pulmonary Diseases: Known or suspected interstitial pneumonia; other severe pulmonary diseases significantly affecting respiratory function within 3 months before the first dose, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia/bronchiolitis obliterans; non-infectious pulmonary inflammation requiring steroid treatment;
13. Infectious Diseases: Positive HIV test; participants with active chronic hepatitis B or active hepatitis C. Carriers of hepatitis B virus, stable hepatitis B after treatment (HBV DNA copy number below the detection limit of the testing center or deemed stable by the investigator), and cured hepatitis C patients (HCV RNA test result below the detection limit of the testing center) may be eligible;
14. Unresolved Adverse Events from Prior Anti-tumor Treatment: Adverse events from prior anti-tumor treatment that have not resolved to ≤ Grade 1 (CTCAE 5.0), except for alopecia or other toxicities deemed non-threatening by the investigator;
15. Severe Infections: Severe infection within 4 weeks before starting study treatment, including but not limited to bacteremia; active infection within 2 weeks before starting treatment requiring intravenous antibiotics;
16. Active Tuberculosis: History or CT evidence of active pulmonary tuberculosis within 1 year before enrollment;
17. Serious Cardiovascular or Cerebrovascular Events: Acute coronary syndrome, congestive heart failure (NYHA functional class ≥ II), aortic dissection, cerebral hemorrhage, stroke, or deep vein thrombosis within 6 months before the first dose;
18. Vaccination: Received live or attenuated vaccines within 30 days before the first dose of study drug, or planned to receive live or attenuated vaccines during the trial;
19. Other Primary Malignancies: History of other primary malignancies within 5 years before the first dose, except for cured basal cell carcinoma, squamous cell carcinoma of the skin, cervical carcinoma in situ, etc;
20. History of Allogeneic Organ or Hematopoietic Stem Cell Transplantation: Known history of allogeneic organ transplant or allogeneic hematopoietic stem cell transplantation；
21. Other Conditions Deemed Ineligible by the Investigator: Such as alcohol or drug abuse, history of significant neurological or psychiatric disorders (e.g., epilepsy, dementia), or poor compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CVL237 tablets; Two predefined doses of CVL237 tablets are set (100 mg/day and 200 mg/day). The starting dose is 100 mg/day, taken orally with food, once daily, continuously, with each treatment cycle lasting 28 days. Participants should take the medication at approximately the same time each day. Serplulimab injection, 200 mg, will be administered via intravenous infusion every 2 weeks. Each 28-day period constitutes one treatment cycle in this study. When dosing on the same day, CVL237 tablets should be taken orally first, followed by an intravenous infusion of Serplulimab at least 30 minutes later. Dose Level 1: CVL237 tablet 100 mg + Serplulimab injection 200 mg, intravenous infusion every 2 weeks; Dose Level 2: CVL237 tablet 200 mg + Serplulimab injection 200 mg, intravenous infusion every 2 weeks.

Drug: CVL237 tablets; CVL237 tablets, 200 mg, taken with food once daily for 28 consecutive days as a treatment cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary study endpoints	Phase Ib: DLT (Dose-Limiting Toxicity)	Up to day 28
Primary Outcome Measure	Phase Ib: RP2D (Recommended Phase 2 Dose)	up to day 28
Primary Outcome Measure	Phase Ib: MTD (Maximum Tolerated Dose) of CVL237 in combination with Serplulimab injection in patients with advanced solid tumors characterized by PTEN loss or low expression;	up to day 28
Primary Study Endpoints	Phase II: Progression-free survival (PFS) assessed according to RECIST v1.1 criteria.	Up to day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Endpoints：	Duration of response (DOR),defined as the time from the first tumor assessment of CR or PR to the first tumor assessment of PD or death due to any cause.	Throughout the study for approximately 2 years
Secondary Study Endpoints	Disease control rate (DCR),which refers to the proportion of patients whose tumors shrink or remain stable for a certain time (mainly for solid tumors), including CR, PR and SD	Throughout the study for approximately 2 years
Secondary Study Endpoints	Progression-free survival (PFS), defined as the time from the start of study treatment to any documented tumor progression or death due to any cause, whichever occurs first;	Throughout the study for approximately 2 years
Secondary Study Endpoints	Overall survival (OS), defined as the time from enrollment to death due to any cause. Efficacy of each tumor type will be analyzed independently.	Throughout the study for approximately 2 years

Collaborators and Investigators

• Sponsor: Convalife (Shanghai) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): January 9, 2028
• Study Completion (Estimated): April 8, 2028

Study Registration Dates

• First Submitted: June 26, 2025
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): March 3, 2026

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; lung cancer; endometrial cancer; ovarian cancer; gastric cancer; cervical cancer; CVL237; Patients with PTEN loss or low expression; Patients with locally advanced or metastatic solid tumors; other tumor types
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Uterine Cervical Diseases; Uterine Neoplasms; Skin and Connective Tissue Diseases; Stomach Neoplasms; Lung Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Uterine Cervical Neoplasms; Endometrial Neoplasms
• Other Study ID Numbers: CVL237-S1001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No