8-K: Mural Oncology Halts Phase 3 Trial of Nemvaleukin in Platinum-Resistant Ovarian Cancer After Disappointing Interim Results

Mural Oncology discontinues the ARTISTRY-7 phase 3 trial of nemvaleukin alfa in combination with pembrolizumab for platinum-resistant ovarian cancer due to failure to achieve statistically significant improvement in overall survival.

Summary

• Mural Oncology has stopped the ARTISTRY-7 phase 3 trial of nemvaleukin alfa combined with Merck's KEYTRUDA (pembrolizumab) for patients with platinum-resistant ovarian cancer (PROC).
• An interim analysis showed that the combination did not significantly improve overall survival compared to investigator's choice chemotherapy.
• Median overall survival was 10.1 months for the nemvaleukin/pembrolizumab group and 9.8 months for the chemotherapy group (hazard ratio: 0.98).
• The company will cease development of nemvaleukin for PROC.
• Nemvaleukin's safety profile remains favorable, with over 800 patients treated across the clinical program.
• The ARTISTRY-6 phase 2 trial of nemvaleukin in mucosal melanoma is ongoing, with topline data expected in the second quarter of 2025.
• Preliminary data for less-frequent intravenous dosing of nemvaleukin in cutaneous melanoma is expected in the second quarter and second half of 2025, depending on the cohort and patient enrollment.

Sentiment

Score: 4

Explanation: The news is negative due to the failed phase 3 trial, but there are ongoing trials and potential future data readouts that offer some hope. The sentiment is cautiously pessimistic.

Positives

• Nemvaleukin has a well-characterized and favorable safety profile, both as a monotherapy and in combination with pembrolizumab, with over 800 patients treated across the broader clinical program.
• The ARTISTRY-6 phase 2 trial of nemvaleukin in mucosal melanoma is ongoing, with topline data expected in the second quarter of 2025.
• Preliminary data readouts for less-frequent intravenous dosing of nemvaleukin in patients with cutaneous melanoma are expected in the second quarter of 2025 for cohort 3 of ARTISTRY-6 (monotherapy) and the second half of 2025 for cohort 4 of ARTISTRY-6 (combination therapy), subject to patient enrollment.

Negatives

• The ARTISTRY-7 phase 3 trial of nemvaleukin in combination with pembrolizumab did not achieve a statistically significant improvement in overall survival versus investigator's choice chemotherapy in patients with platinum-resistant ovarian cancer.
• The company will cease development of nemvaleukin for PROC.

Risks

• The inherent risks and uncertainties associated with competitive developments, preclinical development, clinical trials, recruitment of patients, product development activities and regulatory approval requirements could impact future results.
• Preclinical or interim results and data from ongoing clinical studies may not be predictive of future or final results.
• Future clinical trials may not be initiated or completed on time or at all.
• The company's product candidates, including nemvaleukin, could be shown to be unsafe or ineffective.
• Changes in the cost, scope and duration of development activities could impact the company.
• The U.S. Food and Drug Administration may make adverse decisions regarding the company's product candidates.

Future Outlook

The company is focusing on the ARTISTRY-6 trial in mucosal melanoma and exploring less-frequent intravenous dosing of nemvaleukin in cutaneous melanoma. Data readouts are expected in the second quarter and second half of 2025, subject to patient enrollment.

Industry Context

The discontinuation of the ARTISTRY-7 trial highlights the challenges in developing effective treatments for platinum-resistant ovarian cancer, a difficult-to-treat malignancy. The focus now shifts to other ongoing trials and potential applications of nemvaleukin in different cancer types, such as melanoma.

Comparison to Industry Standards

• The failure of nemvaleukin in combination with pembrolizumab to demonstrate a statistically significant improvement in overall survival in platinum-resistant ovarian cancer contrasts with some successes seen with other immunotherapy combinations in different cancer types.
• For example, some checkpoint inhibitor combinations have shown improved outcomes in certain subsets of ovarian cancer patients, but these successes are often limited to specific biomarkers or patient populations.
• The median overall survival of 10.1 months in the nemvaleukin/pembrolizumab arm is comparable to some chemotherapy regimens used in this setting, but falls short of the more significant improvements seen with targeted therapies in other cancers, such as EGFR inhibitors in lung cancer or HER2-targeted therapies in breast cancer.

Stakeholder Impact

• Shareholders may react negatively to the news of the failed phase 3 trial.
• Patients with platinum-resistant ovarian cancer will not have nemvaleukin as a potential treatment option.
• Employees involved in the nemvaleukin development program for PROC may be affected.

Next Steps

• Continue the ARTISTRY-6 phase 2 trial of nemvaleukin in mucosal melanoma and await topline data in Q2 2025.
• Evaluate preliminary data for less-frequent intravenous dosing of nemvaleukin in cutaneous melanoma in Q2 and H2 2025, subject to patient enrollment.
• Monitor and analyze data from ongoing clinical programs to determine future development strategies for nemvaleukin.

Key Dates

Keywords

nemvaleukin, Mural Oncology, ARTISTRY-7, ARTISTRY-6, pembrolizumab, ovarian cancer, melanoma, clinical trial, phase 3, phase 2, overall survival, chemotherapy