While ESMO 2023 is just around the corner, the leading player in the Pharma industry including AstraZeneca, Pfizer, Novartis, Olema Oncology and Kelun-Biotech, etc. are all geared up for this conference to present the data readouts and final analysis. Breast Cancer is one of the most malignant forms of cancer affecting a large segment of the population in the US with a total incident cases of ~287,000 in 2022. This content provides a brief summary of  Olema’s OP-1250, a small molecule with dual activity as a complete estrogen receptor antagonist (CERAN) and a selective ER degrader (SERD) and Kelun-Biotech’s TROP-2 ADC SKB264 (MK-2870).

Olema is set to revolutionize breast treatment with groundbreaking data from Phase Ib/II clinical study in ER+/HER2– breast cancer. The promising initial results provide strong support that OP-1250 has the potential to provide meaningful benefit to patients with advanced or metastatic breast cancer.

• Abstract Number – #382MO
• Abstract Type - Mini oral session
• Indication – ER+/HER2– breast cancer
• Target – Complete estrogen receptor antagonist (CERAN) and selective ER degrader (SERD)

Olema's lead candidate, OP-1250, offers a powerful dual approach as both a CERAN and a SERD, making it a promising choice for the primary endocrine therapy in the 80% of ER-positive breast cancer cases. It excels at fully blocking the estrogen receptor and signaling pathway while delivering enhanced durability and deeper anti-tumor effects. Palazestrant too, is making waves with its FDA Fast Track designation for treating advanced ER+/HER2– metastatic breast cancer that has progressed despite prior endocrine therapies, even those combined with CDK4/6 inhibitors. In ESM0 2023, Olema will show its most recent results.

In a Phase I/II trial (NCT04505826) of OP-1250 as monotherapy, promising data revealed its safety and effectiveness in patients with HR+/,HER2– breast cancer, showing objective tumor responses and stable disease. Additionally, at the 2023 ESMO Breast Cancer Annual Congress, interim results from the Phase Ib/II study of palazestrant in combination with palbociclib displayed a well-tolerated profile with no dose-limiting toxicities or drug interactions. These findings reinforce the significance of endocrine therapy as the foundation for ER+ breast cancer treatment, with OP-1250 poised to elevate the standard of care across multiple treatment lines. 

The current breakthroughs in this area also include dual PI3K and mTOR inhibitors, AKT inhibitors, SERMS, PI3K inhibitors, PROTAC Degraders, and TROP-2 targeted antibody-drug conjugate. The forthcoming OP-1250 results are poised to revolutionize the breast cancer treatment landscape.

 

Kelun-Biotech to is set to announce latest clinical study results from a Phase I/II basket trial of the innovative TROP2-ADC (SKB264, MK-2870) for treatment of HR+/HER2- breast cancer at ESMO Congress 2023

• Abstract Number - #380MO
• Abstract Type - Mini oral session
• Indication - HR+/HER2–  metastatic breast cancer (mBC)
• Target - TROP2-ADC

SKB264 holds the potential to be a beacon of hope in the clinical realm, particularly as a treatment option for breast cancer. It has a favorable safety profile and has promising anticancer benefits in individuals with HR+/HER2-mBC who have undergone prior treatment. Kelun-Biotech’s basket trial result for HR+/ HER2– metastatic breast cancer (mBC) will mark significant development in breast cancer treatment.

TROP2, often overexpressed in HR+/HER2–mBC, is linked to poor prognosis. SKB264 (also known as MK-2870), an innovative ADC targeting TROP2, was developed by Kelun-Biotech's global ADC R&D platform, OptiDC, using a unique payload-linker approach. It has gained Breakthrough Designations (BTDs) from China's National Medical Products Administration (NMPA) for treating locally advanced or metastatic HR+/HER2– breast cancer after second-line systemic therapy. In the first half of 2023, SKB264's clinical development showed significant progress. As of the data cut-off on April 12, 2023, results from a Phase I/II basket study in HR+/HER2– patients demonstrated a 36.8% ORR, 89.5% DCR, 7.4 months median DoR, 80% 6-month DoR rate, 11.1 months median PFS, and a 61.2% 6-month PFS rate. SKB264 exhibits a well-tolerated safety profile and promising antitumor effects in previously treated HR+/HER2– mBC patients. 

In the landscape of medical advancements, the dynamic SKB264 has emerged as an Antibody-Drug Conjugate (ADC), setting its sights on the TROP2 protein. What sets it apart is its shared monoclonal antibody (mAb) with IMMU-132. Unlike its predecessor, IMMU-132, SKB264 boasts an extended half-life that wields a powerful targeting effect and an impressive anti-tumor prowess. This suggests that SKB264 carries the torch of hope, offering superior therapeutic potential for tackling TROP2-positive tumors. In July 2022, Kelun-Biotech entered into a collaboration and license agreement with MSD to develop an investigational antibody drug conjugate (ADC) for the treatment of solid tumors.

Its remarkable preclinical outcomes have paved the way for its inclusion in clinical trials, raising expectations for potential clinical advantages in patients grappling with gastric carcinoma, lung cancer, and breast cancer. SKB264 has also shown promise even in patients with triple-negative breast cancer (TNBC) who have failed second-line or subsequent standard treatment options, successfully meeting its primary goal. This breakthrough underscores its significance in the medical advancements.