Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Prostatic Neoplasms, Castration-Resistant

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Abiraterone Acetate

Prednisone

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

At the recommended phase II dose of TQB3616 combined with abiraterone acetate (1000 mg, q.d.) plus prednisone (5 mg, b.i.d.), 20-40 patients are planned to be enrolled to evaluate the efficacy and safety of the combination therapy.

Metastatic and genomic tests based on tissue biopsy samples (primary or metastatic) and blood samples will be performed before treatment and after disease progression.

Treatment with TQB3616 in combination with abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer.

TQB3616 Capsules Combined With Abiraterone Acetate Plus Prednisone

Hao Zeng, Doctor

Hao Zeng

This is a phase Ib/II clinical study of TQB3616 capsules in combination with abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer, to determine the dose for further clinical studies and to evaluate the safety and efficacy of this combined therapy.

TQB3616 is an inhibitor of Cyclin-dependent kinases 4 and 6 (CDK4/6), which reduces intracellular protein phosphorylation levels, prevents cells from entering synthesis (S) phase from first gap (G1) phase, and inhibits cell proliferation to combat tumors. TQB3616 has superior inhibitory activity to Palbociclib and Abemaciclib against CDK4/6 kinase and may benefit metastatic castration-resistant prostate cancer (mCRPC) patients through a complementary mechanism of action when combined with abiraterone acetate plus prednisone. Therefore, the investigators intend to perform this phase Ib/II clinical study of TQB3616 capsules in combination with abiraterone acetate plus prednisone in patients with mCRPC.

TQB3616 Capsules Combined With Abiraterone Acetate Plus Prednisone in Metastatic Castration-Resistant Prostate Cancer

Phase Ib/II Clinical Study of TQB3616 Capsules in Combination With Abiraterone Acetate Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer

Biomarker consistency in tumor tissue samples versus blood samples and correlation between biomarkers with efficacy will be analyzed. Biological samples will be collected during the screening period and out of the group, and tested by second-generation sequencing technology. The selected genes are all reported to be related to cell cycle pathways, such as RB1, CDK4/6, CDKN2A (p16 INK4a), CDKN2B (p15 INK4b), CDKN2C (p18 INK4c) and CDKN2D (p19 INK4d), and genes related to AR, TP53, DNA repair pathway, PI3K/AKT signaling pathway, WNT signaling pathway and MAPK signaling pathway, etc., which have been reported to be relevant to prostate cancer treatment.

Percentage of subjects with radiographic progression-free survival of 12 months or more

Radiographic progression-free survival: Refers to the time between the start of enrollment and the onset of disease imaging progression or recurrence or death from all causes, whichever occurs first. Imaging-confirmed disease progression includes: soft tissue and lymph node disease progression as evaluated by Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1), and bone metastases progression as evaluated by the Prostate Cancer Working Group 3 (PCWG3) .

Percentage of subjects with radiographic progression-free survival of 6 months.

The percentage of subjects whose PSA decrease by more than 50% of the baseline value and maintain for more than 4 weeks.

The time from the first dose to the confirmation of PSA progression. The PCWG3 standard defines PSA progression as: For subjects with a ≥50% decrease in PSA at 12 weeks of treatment, a 25% increase in PSA above the nadir and an absolute increase of ≥2 ng/mL compared to the nadir, and confirmed by a second PSA test ≥3 weeks later; for subjects with a non-responsive PSA at 12 weeks of treatment, a 25% increase in PSA above baseline and an absolute increase of ≥2 ng/mL compared to the baseline value, and confirmed by a second PSA test ≥3 weeks later.

Objective response rate: The percentage of subjects in complete response (CR) or partial response (PR) as determined by the investigator according to RECIST 1.1.

Overall survival: The time between the start of enrollment and death from all causes.

Clinical benefit rate: The best overall outcome (BOR) was the proportion of stable disease (SD) subjects with CR, PR and duration ≥24 weeks as rated by RECIST 1. 1 criteria.

Duration of response: For subjects whose best remission was CR or PR, this is defined as the time between the date of first documented tumor remission and the date of first documented disease progression or death from any cause, whichever occur first.

Spots Global Cancer Trial Database for tqb3616 capsules combined with abiraterone acetate plus prednisone