RemeGen Reports Proof-of-Concept Phase I/II Clinical Study Results for Self-Developed, Potential First-in-Class Antibody-Drug Conjugate RC88

Rhea-AI Summary

RemeGen presented results from a Phase I/II clinical study of RC88, an antibody-drug conjugate targeting mesothelin (MSLN) in advanced solid tumors. The study included 170 patients with ovarian cancer, non-squamous non-small cell lung cancer, and cervical cancer who had failed standard therapies.

Key findings include:

- Ovarian cancer cohort: 45.2% overall response rate (ORR) and a median duration of response (DoR) of 8.02 months.

- Non-squamous non-small cell lung cancer cohort: 31.3% ORR and a median progression-free survival (PFS) of 6.87 months.

- Cervical cancer cohort: 33.3% ORR with a median DoR of 9.13 months.

These promising results suggest RC88's potential in improving outcomes for MSLN-expressing tumors.

Positive

• High overall response rate (ORR) in ovarian cancer cohort at 45.2%.
• Median duration of response (DoR) in ovarian cancer cohort is 8.02 months.
• Non-squamous non-small cell lung cancer cohort shows a 31.3% ORR.
• Median progression-free survival (PFS) in lung cancer cohort is 6.87 months.
• Cervical cancer cohort achieved a 33.3% ORR.
• Median DoR for cervical cancer cohort is 9.13 months.
• RC88 shows promising efficacy in MSLN-expressing advanced solid tumors.
• Phase II study includes expanded doses of 2.0 mg/kg and 2.5 mg/kg.

Negative

• The study is a single-arm, open-label design, which may limit the robustness of the data.
• High prior exposure to other treatments (bevacizumab, PARPi) in ovarian cancer cohort could confound results.
• patient sample sizes in lung cancer (16 patients) and cervical cancer (18 patients) cohorts may affect the generalizability of the findings.
• Potential for side effects and adverse reactions remains to be fully understood.

YANTAI, China, June 3, 2024 /PRNewswire/ -- RemeGen Co., Ltd. ("RemeGen" or "the Company") (9995.HK, SHA: 688331), a commercial-stage biotechnology company, presented the results of the first-in-human, single-arm, open-label, multi-center Phase I/II study evaluating RC88 in patients with MSLN-expressing advanced solid tumors on June 3, at the American Society of Clinical Oncology Annual Meeting (ASCO 2024) held in Chicago from May 31-June 4, 2024. The first author, Professor Liu Yutao, from the Chinese Academy of Medical Sciences Cancer Hospital, presented RemeGen's poster session (Poster #422) of this study that focused on efficacy and safety in patients with ovarian cancer, non-squamous non-small cell lung cancer, and cervical cancer.

RC88 is a novel, first-in-class, antibody-drug conjugate (ADC) developed by RemeGen that targets mesothelin (MSLN) with a monomethyl auristatin E (MMAE) payload. MSLN, a glycosylphosphatidylinositol-anchored protein, is overexpressed in several solid tumors with limited expression in normal tissues. RC88 consists of a recombinant humanized anti-MSLN monoclonal antibody linked to MMAE which acts as a microtubule inhibitor. RC88 has a high affinity for MSLN and can specifically bind to MSLN overexpressing tissues. In this study, RC88 has demonstrated a terminating effect on tumor cells with various levels of MSLN expression. RC88 has demonstrated anti-tumor activity and a manageable RC88 monotherapy safety profile in MSLN-positive advanced solid tumors. Preclinical studies showed that RC88 can selectively deliver a potent cytotoxic payload to MSLN-expressing cells through internalization, thus inducing G2/M arrest and apoptosis.

Patients with MSLN-expressing advanced malignant solid tumors that had failed standard therapies were enrolled in this study. For the Phase II study, the primary endpoint was overall response rate (ORR) per RECIST v1.1 criteria-based endpoints, with secondary endpoints including disease control rate (DCR), progression-free survival (PFS), and safety.

As of February 21, 2024, 170 patients with advanced solid tumor were enrolled. The dose escalation phase was completed, and 2.0 mg/kg and 2.5 mg/kg Q3W doses were expanded into Phase II.

In the ovarian cancer (OC) cohort, 54 patients were enrolled, all with 2+ or 3+ MSLN expression. Of these, 40 (74.1%) had an ECOG score of 1; 33 (61.1%) had received prior bevacizumab treatment, and 28 (51.9%) had prior PARP inhibitor (PARPi) exposure. As of March 22, 2024, a total of 31 patients in the 2.0mg/kg group who had received two to four lines of prior therapies were efficacy-evaluable. Among them, the ORR and confirmed ORR (cORR) were 45.2% (14/31, 95%CI 27.3, 64.0) and 41.9% (13/31, 95%CI 24.5, 60.9), respectively. The median DoR was 8.02 months (95%CI 2.83, 8.54).

In the non-squamous non-small cell lung cancer (NSCLC) cohort, 16 EGFR/ALK wild-type (WT) patients were efficacy-evaluable. The ORR and cORR were 31.3% (5/16) and 25% (4/16), respectively. Among the above patients with MSLN high expression (PS2^#≥50), the ORR, cORR, median PFS and median DoR were 41.7% (5/12), 33.3% (4/12), 6.87 months and 9.13 months, respectively.

In the cervical cancer (CC) cohort, 18 patients who had progressed on previous systemic therapies were enrolled. The ORR and cORR were 33.3% (6/18) and 27.8% (5/18), respectively. Among the 12 patients that received ≥ 2 lines of therapies, the ORR and cORR were 41.7% (5/12) and 33.3% (4/12), respectively.

"Currently, chemotherapy is the standard of care for OC with an ORR rate of 12%. The promising results of 41.9% ORR from this study underscore the potential of RC88 to significantly improve outcomes for patients with MSLN-expressing advanced solid tumors," said Dr. Fang Jianmin, CEO of RemeGen. "We are committed to advancing our innovative therapies to address these huge unmet medical needs and enhance patient care."

About RemeGen Co. Ltd.

Founded in 2008, RemeGen (9995.HK, SHA: 688331) is a leading biopharmaceutical company in China committed to providing solutions to the unmet clinical needs of patients suffering from life-threatening illnesses. RemeGen has research laboratories and offices throughout China and the United States. The company is committed to discovering, developing, and commercializing innovative and differentiated biologic drugs of significant clinical value in the key therapeutic areas of autoimmune, oncology, and ophthalmic diseases. For more details, please visit: www.remegen.com

About RC88

Independently developed by RemeGen, RC88 is a novel antibody drug conjugate (ADC) targeting mesothelin (MSLN). It uses the company's innovative bridging technology to connect antibodies and payloads. By design,  RC88 molecule can mediate the endocytosis of antibodies by binding to MSLN-positive tumor cells, thereby effectively delivering cytotoxins to cancer cells and achieving improved tumor killing effects.

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SOURCE RemeGen Co., Ltd

FAQ

What is the overall response rate (ORR) of RC88 in ovarian cancer?

The overall response rate (ORR) of RC88 in the ovarian cancer cohort is 45.2%.

What is the median duration of response for RC88 in ovarian cancer?

The median duration of response (DoR) for RC88 in the ovarian cancer cohort is 8.02 months.

What is the ORR for RC88 in non-squamous non-small cell lung cancer (NSCLC)?

The ORR for RC88 in the non-squamous non-small cell lung cancer cohort is 31.3%.

What is the median progression-free survival (PFS) for RC88 in NSCLC?

The median progression-free survival (PFS) for RC88 in the NSCLC cohort is 6.87 months.

How effective is RC88 in treating cervical cancer?

RC88 has an overall response rate (ORR) of 33.3% in the cervical cancer cohort.

What is the sample size of the RC88 study in cervical cancer?

The cervical cancer cohort in the RC88 study includes 18 patients.

What doses were used in the Phase II study of RC88?

The Phase II study of RC88 used doses of 2.0 mg/kg and 2.5 mg/kg.

What types of cancer were included in the RC88 Phase I/II study?

The RC88 Phase I/II study included ovarian cancer, non-squamous non-small cell lung cancer, and cervical cancer.