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This is a single-arm, open-label, multicenter, phase II study of CVL237 tablets in the treatment of advanced solid tumors with PTEN deficiency.All patients will be given CVL237 tablets, 200 mg, taken with food once daily for 28 consecutive days as a treatment cycle.

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

CVL237 tablets

Ning Li, post doctorate

Shuhang Wang

Li Ning

This is a single-arm, open-label, multicenter, phase II study of CVL237 tablets in the treatment of advanced solid tumors with PTEN deficiency. It is planned to enroll patients with PTEN deficiency advanced solid tumors of different tumor types (PTEN deficiency gastric cancer, prostate cancer, endometrial cancer, colorectal cancer, lung cancer, breast cancer and melanoma etc.) to evaluate the preliminary efficacy, safety and pharmacokinetic profile of CVL237 tablets in patients with PTEN deficiency advanced solid tumors of different tumor types.

"The predicted BSC (best supportive care treatment) ORR is 0.5% and the post-treatment ORR is 15% with 80% certainty and a significance level of 0.05 (bilateral). The first stage: After testing the drug on 10 patients in the first stage, the trial will be terminated if 0 respond; if any subject showed respond then enter the second stage; The second stage: If the trial goes on to the second stage, another 4 evaluation subjects could continue to be enrolled, a total of 14 patients will be studied. If the total number responding is less than or equal to 0, the drug is rejected.. If a subject falls off during the trial, i.e., the objective remission cannot be judged, the number of subjects should be completed.

The maximum number of qualified subjects for the 7 tumor types is 98 (in the best case, according to clinical practice, it is recommended to enroll a certain number of subjects for each tumor type, not exceeding 14).

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

Tumors will be evaluated according to the Solid Tumor Efficacy Evaluation Criteria (RECIST version 1.1 criteria) and will be assessed every 2 cycles. Tumor assessment may be increased by the investigator as clinically indicated. Treatment periods may be administered continuously until the onset of intolerable adverse effects, disease progression, withdrawal of informed consent (ICF), lost to follow-up, death, or study termination, whichever occurs earliest. Efficacy of each tumor type will be analyzed independently.

Withdrawal from the study/termination of treatment for any reason required return to the study center for safety follow-up 30 days (±3 days) after the last dose. Patients will then enter a survival follow-up period until the full 2 years after the end of the trial/missing/death. All patients will be followed up every 12 weeks (±5 days) for survival, either by telephone with the subject, their family or local hospital.

Pharmacokinetic studies will be performed in 6-12 patients."

CVL237 Tablets in the Treatment of Advanced Solid Tumors With PTEN Deficiency

A Single-arm, Open-label, Multicenter, Phase II Study of CVL237 Tablets in the Treatment of Advanced Solid Tumors With PTEN Deficiency

objective response rate (ORR), which refers to the proportion of patients whose tumor shrinkage reaches a certain amount and maintains for a certain time, including complete response (CR) and partial response (PR)

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.

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

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;

Overall survival (OS), defined as the time from enrollment to death due to any cause. Efficacy of each tumor type will be analyzed independently.

Convalife (Shanghai) Co., Ltd.

Immune System Diseases

Hypersensitivity

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antineoplastic Agents

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Androgens

Hormones

Abiraterone Acetate

Prednisone

Prednisolone

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Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Enzyme Inhibitors

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Cytochrome P-450 Enzyme Inhibitors

Participants receive capivasertib in combination with abiraterone (prednisone/prednisolone) on a background of ADT.

Participants receive placebo in combination with abiraterone (prednisone/prednisolone) on a background of ADT.

400 mg (2 tablets) BD given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle. Number of Cycles: until disease progression or unacceptable toxicity develops.

Capivasertib

matched to capivasertib appearance (2 tablets) BD given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle. Number of Cycles: until disease progression or unacceptable toxicity develops.

Placebo

Administered orally as tablets at a dosage of 1000 mg daily. Administered continuously until criteria for discontinuation are met.

This study will assess the efficacy and safety of capivasertib plus abiraterone (+prednisone/prednisolone) plus androgen deprivation therapy (ADT) versus placebo plus abiraterone (+prednisone/prednisolone) plus ADT in participants with mHSPC whose tumours are characterised by PTEN deficiency. The intention of the study is to demonstrate that in participants with mHSPC, the combination of capivasertib plus abiraterone (+prednisone/prednisolone) plus ADT is superior to placebo plus abiraterone (+prednisone/prednisolone) plus ADT in participants with mHSPC characterised by PTEN deficiency with respect to radiographic progression-free survival (rPFS) per 1) Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for soft tissue and/or Prostate Cancer Working Group (PCWG3) for bone as assessed by the investigator 2) death due to any cause.

Approximately 1000 participants are assigned to one of the two parallel groups (1:1 ratio) to receive either capivasertib or placebo, in combination with abiraterone on a background of ADT for the duration of the study.

Capivasertib+Abiraterone as Treatment for Patients With Metastatic Hormone-sensitive Prostate Cancer and PTEN Deficiency

A Phase III Double-Blind, Randomised, Placebo-Controlled Study Assessing the Efficacy and Safety of Capivasertib+Abiraterone Versus Placebo+Abiraterone as Treatment for Patients With DeNovo Metastatic Hormone-Sensitive Prostate Cancer Characterised by PTEN Deficiency.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

Percentage of participants with an adverse event (AE), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0, including analysis of pre-specified AEs.

Change from baseline in selected laboratory test results

rPFS is defined as the time from randomisation to radiographic progression, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST) for soft tissue and/or Prostate Cancer Working Group 3 (PCWG3) for bone, or death due to any cause for each study arm.

Overall survival is the length of time from randomisation until the date of death due to any cause.

TFST is defined as time from randomisation to the earlier of: the start date of the first subsequent anticancer therapy after discontinuation of randomised treatment (capivasertib/placebo), or death due to any cause.

SSE-FS is defined as time from randomisation until any of the following: use of radiation therapy to prevent or relieve skeletal symptoms; Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral); Occurrence of spinal cord compression; Orthopaedic surgical intervention for bone metastasis; Death due to any cause.

TTPP is defined as the time from randomisation to clinically meaningful pain progression base on a 2-point increase from baseline in the Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("worst pain in 24 hours") score and/or initiation of/increase in opiate analgesic use.

The time from randomisation to PSA progression, as determined by PCWG3 criteria.

TTCR is defined as the time from randomisation to the first castration-resistant event (radiographic disease progression, PSA progression, or SSE), whichever occurs first, with castrate levels of testosterone (below 50 ng/dL).

BFI endpoints may include: Time to deterioration in fatigue intensity; Time to deterioration in fatigue interference; Change from baseline in fatigue severity and fatigue interference domain scores.

BPI-SF: Change from baseline in pain severity and pain interference domain scores.

FACT-P endpoints may include: Time to deterioration in FACT-P scores; Change from baseline in FACT-P scores.

PFS2 is defined as time from randomisation until progression on next-line treatment, as clinical progression, PSA progression, or radiographic progression determined by RECIST version 1.1 (soft tissue) and/or PCWG3 criteria (bone), as assessed by the investigator, or death due to any cause.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CVL237 Tablets in the Treatment of Advanced Solid Tumors With PTEN Deficiency	NCT06183736	Advanced Solid ...	CVL237 tablets	18 Years - 75 Years	Convalife (Shanghai) Co., Ltd.
CVL237 Tablets in the Treatment of Advanced Solid Tumors With PTEN Deficiency	NCT06183736	Advanced Solid ...	CVL237 tablets	18 Years - 75 Years	Convalife (Shanghai) Co., Ltd.
Capivasertib+Abiraterone as Treatment for Patients With Metastatic Hormone-sensitive Prostate Cancer and PTEN Deficiency	NCT04493853	Hormone-Sensiti...	Capivasertib Placebo Abiraterone Ace...	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for pten deficiency