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

NCT07446049 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: CVL237-S1001
• Study Type: interventional
• Target: 180
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Locally Advanced or Metastatic Solid Tumors; PTEN Loss or Low Expression

Keywords

CVL237; Patients with PTEN loss or low expression; Patients with locally advanced or metastatic solid tumors; gastric cancer; endometrial cancer; cervical cancer; ovarian cancer; lung cancer; breast cancer; other tumor types

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• Secondary Endpoints：

  Throughout the study for approximately 2 years

• Secondary Study Endpoints

  Throughout the study for approximately 2 years

• Secondary Study Endpoints

  Throughout the study for approximately 2 years

• Secondary Study Endpoints

  Throughout the study for approximately 2 years

Study Arms (1)

CVL237 tablets

EXPERIMENTAL

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

Interventions

CVL237 tablets DRUG

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

CVL237 tablets

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 75 years (inclusive of both endpoints), regardless of gender；
• 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;
• 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;
• ECOG Performance Status (PS) of 0-1;
• Life expectancy of ≥3 months;
• Presence of at least one measurable lesion according to RECIST v1.1 criteria;
• 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):
• 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;
• Voluntarily participating in this clinical trial, understanding the study procedures, and being able to provide written informed consent.

You may not qualify if:

• 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;
• Insufficient Washout Period for Prior Anti-tumor Treatments;
• Inability to Swallow, Chronic Diarrhea, or Bowel Obstruction: Presence of factors that may affect the intake and absorption of the study drug;
• 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;
• Uncontrolled Effusions: Presence of uncontrolled pleural effusion, ascites, or pericardial effusion;
• 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;
• 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;
• History of Severe Allergic Reactions: Known history of severe allergic reactions to multiple medications;
• Immune-related Adverse Events (irAEs): Participants who experienced ≥ Grade 3 irAEs or ≥ Grade 2 immune-related myocarditis during prior immunotherapy are not eligible;
• 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;
• 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);
• 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;
• 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;
• 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;
• 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;

Sponsors & Collaborators

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

MeSH Terms

Conditions

Stomach Neoplasms; Endometrial Neoplasms; Uterine Cervical Neoplasms; Ovarian Neoplasms; Lung Neoplasms; Breast Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Uterine Cervical Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2025
• First Posted: March 3, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): January 9, 2028
• Study Completion (Estimated): April 8, 2028
• Last Updated: March 3, 2026

Record last verified: 2026-02