Promising New Antibody-Drug Conjugate Shows Potential for Treating Advanced Solid Tumors

Introduction to RC88: A New Hope in Cancer Treatment

RemeGen Co., Ltd., a front-runner in biotechnology, has unveiled encouraging results from their Phase I/II clinical trial for RC88, a pioneering antibody-drug conjugate (ADC). This novel therapy targets mesothelin (MSLN), a protein found in abundance in several types of tumors but limited in normal tissues.

Presented at the American Society of Clinical Oncology Annual Meeting (ASCO 2024) in Chicago, the results are a significant step towards offering new treatment options for patients with advanced solid tumors who have exhausted standard therapies.

Details of the Clinical Study

The clinical trial was designed as a first-in-human, single-arm, open-label, multi-center study. It evaluated RC88's safety and effectiveness in patients with MSLN-expressing advanced solid tumors, such as ovarian cancer, non-squamous non-small cell lung cancer (NSCLC), and cervical cancer.

The study enrolled 170 patients whose tumors overexpressed MSLN and who had not responded to existing treatments. The trial explored different dosing regimens, ultimately selecting 2.0 mg/kg and 2.5 mg/kg given every three weeks (Q3W) for further evaluation in Phase II.

Mechanism of Action of RC88

RC88 is a combination of a recombinant humanized monoclonal antibody and monomethyl auristatin E (MMAE), a potent cytotoxic agent. This ADC specifically targets MSLN-expressing cells and delivers the cytotoxin directly into the cancer cells, resulting in cell cycle arrest and apoptosis (programmed cell death).

Preclinical studies revealed that RC88 effectively binds to MSLN, is internalized by the cancer cells, and releases its cytotoxic payload to eliminate the tumor cells.

Results in Ovarian Cancer Patients

In the ovarian cancer cohort, 54 patients who had 2+ or 3+ MSLN expression participated. Preliminary results showed promising efficacy, with an objective response rate (ORR) of 45.2% among 31 evaluable patients. The median duration of response (DoR) was approximately eight months, indicating a sustained therapeutic effect.

Importantly, the safety profile of RC88 in this cohort was found to be manageable, offering a potentially new and effective treatment option for ovarian cancer patients who have exhausted other therapies.

Results in Non-Squamous Non-Small Cell Lung Cancer Patients

The NSCLC cohort included 16 patients. The study observed an ORR of 31.3%, with a confirmed ORR of 25%. Among patients with high MSLN expression, the ORR was even more encouraging at 41.7%, and the median progression-free survival (PFS) was reported to be 6.87 months.

These results suggest that RC88 could be a viable option for NSCLC patients who have limited treatment options after standard therapies have failed.

Results in Cervical Cancer Patients

Eighteen patients with advanced cervical cancer who had progressed on previous treatments were included in this cohort. The ORR was 33.3%, with a confirmed ORR of 27.8%. For patients who had received two or more lines of therapy, the ORR improved to 41.7%.

This interim data supports the potential for RC88 to provide substantial benefit to cervical cancer patients with high MSLN expression who have limited therapeutic options.

Expert Opinions and Future Directions

Dr. Fang Jianmin, CEO of RemeGen, highlighted the significance of these findings, emphasizing RC88's potential to surpass the efficacy of traditional chemotherapy, especially in ovarian cancer where ORR can be as low as 12%.

RemeGen is dedicated to advancing RC88 through further clinical development, with hopes of extending its benefits to a broader patient population facing MSLN-expressing cancers.