culmerciclib (TQB3616) / Sino Biopharm - LARVOL DELTA

CDK4/6 Inhibitor Can Improve Niraparib Sensitivity and Reverse Acquired Drug Resistance Through Endonuclease G Nuclear Translocation in BRCA Wild-Type Ovarian Cancer: A Vitro Study. (PubMed, BJOG) - "Combined therapy with the CDK4/6 inhibitor TQB-3616 and niraparib ZL-2306 showed synergistic antitumour effects against BRCA wild-type ovarian cancer without increasing the toxicity of each drug. The antitumour effect may be related to mitochondrial apoptosis, where EndoG nuclear translocation plays a critical role. This study proposes combined therapy of CDK4/6 and PARP inhibitors as a novel approach for the treatment of refractory ovarian cancer."

Journal • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • BRCA

Clinical Trial of Evaluating TQB3912 Tablets Combined With Fulvestrant Injection±TQB3616 Capsules for Locally Advanced or Metastatic Hormone Receptor(HR)-Positive and Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=75 | Not yet recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

New P1/2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

[Important] Clinical data of 9 new class 1 drugs are released for the first time, and tumors, diabetes, weight loss, etc. are very popular in the field [Google translation] (bydrug.pharmcube.com) - "TQB3616: Zhengda Tianqing's first oral CDK2/4/6 inhibitor...Compared with abemaciclib, this product has a further enhanced inhibitory effect on CDK2. Its enhanced CDK2 and CDK4 inhibitory activity may help overcome the current CDK4/6 inhibitor resistance problem in clinical practice."

Clinical data • Oncology • Solid Tumor

TRIM4 modulates the ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitor in ovarian cancer. (PubMed, Front Med) - "Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616...Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer."

Journal • Oncology • Ovarian Cancer • Solid Tumor • Targeted Protein Degradation • CDKN2C • HNRNPD • TRIM4

Evaluation of TQB3616 Capsules in a Phase II Clinical Trial for Recurrent/Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=33 | Not yet recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Metastases • New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Drug-Drug Interaction (DDI) Study for TQB3616 (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

New P1 trial

Two new breast cancer drugs from Zhengda Tianqing approved for clinical trials [Google translation] (bydrug.pharmcube.com) - "On October 22, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration announced that two Class 1 new drugs of Zhengda Tianqing have obtained implicit approval for clinical trials. The indications are TQB3616 capsules combined with TQB3912 tablets and Fulvestrant injection for the treatment of advanced HR-positive, HER2-negative breast cancer."

New trial • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology

TQB3616 combined with fulvestrant in the treatment of hormone receptor-positive, HER2-negative advanced breast cancer: a randomized, double-blind, parallel-controlled phase 3 clinical trial (CSCO 2024) - "Study group: [Organizing Committee]"

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Sino Biopharmaceutical (01177): Phase III study data of culmerciclib capsule combined with Fulvestrant injection for the treatment of HR+/HER2- advanced breast cancer treated with endocrine therapy will be announced at 2024 CSCO [Google translation] (Zhitong Finance) - P3 | N=287 | NCT05375461 | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | "It is used in combination with Fulvestrant injection to treat endocrine-treated hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer: the median progression-free survival (PFS) was 16.62 months, the objective response rate (ORR) was 40.21%, and the overall survival (OS) showed a beneficial trend...Compared with the control group, the median PFS of culmerciclib combined with Fulvestrant was extended by 9.16 months, and the risk of disease progression/death was reduced by 64% (HR=0.36, P<0.0001). The main research results of median PFS, hazard ratio (HR) and absolute benefit of PFS were all higher than the data of existing standard treatment."

P3 data • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

TQB3616-III-01: TQB3616 Capsules Plus Fulvestrant Compared to Placebo Plus Fulvestrant in Previously Treated Breast Cancer in Clinical Trail (clinicaltrials.gov) - P3 | N=287 | Active, not recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2023 ➔ Dec 2025

Enrollment closed • Metastases • Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Phase II study of the CDK2/4/6 inhibitor TQB3616 capsules in patients with dedifferentiated liposarcomas (DDLPS) (ESMO 2024) - P2 | "CDK2/4/6 inhibitor TQB3616 has shown therapeutic potential in DDLPS. Based on the good efficacy and safety of single-arm part, the randomized, double-blind part has been approved by National Medical Products Administration (NMPA)."

Clinical • P2 data • Liposarcoma • Oncology • Sarcoma • Solid Tumor

Six innovative Chinese biopharmaceutical drugs were unveiled at the World Lung Cancer Conference to empower patients with treatment [Google translation] (Sohu.com) - "In 2025, several blockbuster products of Sino Biopharmaceuticals are expected to be approved for marketing. Among them, KRAS G12C inhibitor D-1553 is the first of its kind in China, and is expected to fill clinical and market gaps; CDK2/4/6 inhibitor TQB3616 is a new generation of therapy for HR+/HER- breast cancer, and is expected to become the best product of its kind; the first domestically launched pertuzumab biosimilar next year is expected to be combined with the already launched trastuzumab to form a 'trastuzumab' combination, which is expected to bring new hope to HER2-positive breast cancer patients."

Approval • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Sino Biopharmaceutical (01177): Data from a Phase III study of culmerciclib combined with Fulvestrant in the treatment of HR+/HER2- advanced breast cancer patients who have undergone endocrine therapy will be announced at CSCO 2024 [Google translation] (Zhitong Finance) - "According to the Zhitong Finance APP, China Biopharmaceutical Co., Ltd. (01177) issued an announcement that the innovative drug 'culmerciclib Capsule (TQB3616)' independently developed by the group will be announced at the National Conference of Clinical Oncology and the 2024 CSCO Academic Annual Meeting (2024 CSCO) held from September 25 to 29. The latest results of the Phase III study (TQB3616-III-01) will be announced for combination with Fulvestrant for the treatment of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer who have been treated with endocrine therapy."

P3 data • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

PHASE III STUDY RESULTS OF CULMERCICLIB IN COMBINATION WITH FULVESTRANT FOR TREATMENT OF HR+/HER2- ADVANCED BREAST CANCER FOLLOWING ENDOCRINE TREATMENT TO BE PRESENTED AT 2024 CSCO (Sino Biopharm Press Release) - "The board of directors...of Sino Biopharmaceutical Limited...together with its subsidiaries...announces that the latest results of the phase III study of the innovative drug “Culmerciclib (TQB3616)” self-developed by the Group in combination with Fulvestrant for the treatment of patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer following endocrine treatment (TQB3616-III-01) will be presented at the National Congress of Clinical Oncology and 2024 CSCO Annual Meeting (2024 CSCO) to be held on 25th to 29th of September....The results of the study revealed that Culmerciclib had an inhibitory impact on CDK2, and its enhanced CDK2 and CDK4 inhibitory effects may help to overcome the prevailing problem of resistance to CDK4/6 inhibitors in the clinical setting."

P3 data • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Discovery and preclinical evaluations of TQB3616, a novel CDK4-biased inhibitor. (PubMed, Bioorg Med Chem Lett) - P3 | "Among small-molecule CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) approved for metastatic breast cancers, abemaciclib has a more tolerable adverse effects in clinic. These differentiated properties, together with excellent GLP safety profile warranted TQB3616 moving to clinic. TQB3616 entered into clinical development in 2019 and currently in phase III clinical trials (NCT05375461, NCT05365178)."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor

A Study of TQB2930 for Injection Monotherapy or Combination Therapy in Patients With Recurrent/Metastatic Breast Cancer (clinicaltrials.gov) - P1/2 | N=154 | Recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | N=89 ➔ 154 | Trial completion date: Oct 2025 ➔ Oct 2027 | Trial primary completion date: Mar 2025 ➔ Dec 2026

Combination therapy • Enrollment change • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

To Evaluate the Efficacy and Safety of TQB3616 in Combination With Fulvestrant Versus Placebo in Combination With Fulvestrant in Previously Untreated Hormone-receptor (HR)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=432 | Active, not recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Not yet recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

The Potent Novel CDK4/6 Inhibitor TQB3616 in Hormone Receptor Positive Breast Cancer: Preclinical Characterization with in vitro and Human Tumor Xenograft Models [Letter]. (PubMed, Breast Cancer (Dove Med Press)) - No abstract available

Journal • Preclinical • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

The Potent Novel CDK4/6 Inhibitor TQB3616 in Hormone Receptor Positive Breast Cancer: Preclinical Characterization with in vitro and Human Tumor Xenograft Models. (PubMed, Breast Cancer (Dove Med Press)) - "Oral administration of TQB3616 showed more potent antitumor activity than abemaciclib in an in vitro breast cancer xenograft model, causing significant tumor regression associated with sustained target inhibition in tumor tissue and manageable in vivo toxicity. The results of this study indicate that TQB3616 is a novel CDK4/6 inhibitor, and its highly effective antitumor activity against breast cancer is expected to yield promising therapeutic effects in clinical studies."

Journal • Preclinical • Breast Cancer • Endocrine Cancer • Estrogen Receptor Positive Breast Cancer • Eye Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • ER

The Potent Novel CDK4/6 Inhibitor TQB3616 in Hormone Receptor Positive Breast Cancer: Preclinical Characterization with in vitro and Human Tumor Xenograft Models (Dovepress) - "TQB3616 showed a remarkable inhibitory effect on the proliferation of hormone receptor-positive breast cancer cells in vitro. In addition, TQB3616 combined with endocrine therapy or Human Epidermal Growth Factor Receptor 2 (HER2) targeted therapy showed significant synergistic antitumor activity in estrogen receptor (ER)-positive/HER2-negative or HER2-positive breast cancer. In contrast to abemaciclib, which targets the CDK4/6 pathway with proven efficacy, the oral agent TQB3616 not only induced G1 stalling, leading to a profound reduction in the level of RB protein phosphorylated at Ser807/811, but also showed enhanced tumor killing effects by promoting cell apoptosis."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Mass Balance Study of TQB3616 (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

New P1 trial • Breast Cancer • Oncology • Solid Tumor

Clinical Study on Adjuvant Therapy of TQB3616 Combined With Endocrine Therapy Compared With Placebo Combined With Endocrine Therapy in Patients With Breast Cancer (clinicaltrials.gov) - P3 | N=1946 | Recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Clinical Study on Adjuvant Therapy of TQB3616 Combined With Endocrine Therapy Compared With Placebo Combined With Endocrine Therapy in Patients With Breast Cancer (clinicaltrials.gov) - P3 | N=1946 | Not yet recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

TQB3616 Capsules in the Treatment of Dedifferentiated Liposarcoma (clinicaltrials.gov) - P2 | N=118 | Not yet recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

New P2 trial • Liposarcoma • Oncology • Sarcoma • Solid Tumor

TQB3616 Capsules Plus Fulvestrant Compared to Placebo Plus Fulvestrant in Previously Treated Breast Cancer in Clinical Trail (clinicaltrials.gov) - P3 | N=287 | Recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2