8-K: Delcath CHOPIN Trial Results Published in Lancet Oncology

Delcath Systems announced the publication of positive CHOPIN clinical trial results in The Lancet Oncology, highlighting the promise of combining percutaneous hepatic perfusion with immunotherapy for metastatic uveal melanoma.

Summary

• Full results from the investigator-initiated CHOPIN randomized Phase 2 clinical trial, led by Professor Ellen Kapiteijn, MD, from Leiden University Medical Centers, have been published in The Lancet Oncology.
• The trial randomized 76 patients with metastatic uveal melanoma (mUM) to percutaneous hepatic perfusion (PHP) with melphalan (Delcath's CHEMOSAT Hepatic Delivery System) alone or in combination with ipilimumab plus nivolumab.
• The combination arm demonstrated a 1-year progression-free survival (PFS) of 54.7% compared to 15.8% for PHP-alone (adjusted HR 0.34; 95% CI 0.19-0.60; p=0.0002).
• Median PFS was 12.8 months in the combination arm versus 8.3 months in the PHP-alone arm.
• Overall Survival (OS) median was 23.1 months in the combination arm versus 19.6 months in the PHP-alone arm (HR 0.39; 95% CI 0.20-0.77; p=0.0065).
• The 2-year OS rate was 49.6% for the combination arm compared to 22.1% for PHP-alone.
• Objective Response Rate (ORR) was 76.3% in the combination arm versus 39.5% in the PHP-alone arm, with a Complete Response (CR) rate of 13% versus 3%.
• Grade 3 or higher treatment-related adverse events occurred significantly more frequently in the combination arm (82%) than in the PHP-alone arm (41%); p=0.0006, which was similar to the rate reported in the FOCUS trial (81%).
• Common grade 3/4 events included thrombocytopenia (34% vs 14%), leukopenia (26% vs 14%), g-glutamyl transferase increase (18% vs 8%), and anemia (13% vs 3%).
• Most adverse events were self-limiting or manageable with standard supportive care, and no new safety signals were identified.
• One treatment-related death (immune-related triple M syndrome) occurred in the combination arm.

Sentiment

Score: 8

Explanation: StockSavvy.ai views this as a highly positive development, as the publication of strong Phase 2 clinical trial results in a top-tier medical journal validates the efficacy of Delcath's combination therapy and significantly improves patient outcomes in a difficult-to-treat cancer.

Positives

• The combination therapy more than tripled the 1-year progression-free survival rate (54.7% vs 15.8%) compared to PHP-alone.
• The combination therapy nearly doubled the 2-year overall survival rate (49.6% vs 22.1%) compared to PHP-alone.
• Significantly improved Objective Response Rate (76.3% vs 39.5%) and Complete Response rate (13% vs 3%) with the combination therapy.
• The detailed analyses reinforce the synergistic potential of combining PHP with immunotherapy, showing enhanced hepatic control and deeper, more durable responses.
• No new safety signals were identified, and most adverse events were manageable with standard supportive care.

Negatives

• Grade 3 or higher treatment-related adverse events occurred significantly more frequently in the combination arm (82%) compared to the PHP-alone arm (41%).
• One treatment-related death (immune-related triple M syndrome) occurred in the combination arm.

Risks

• Uncertainties relating to the Company’s commercialization plans and its ability to successfully commercialize the HEPZATO KIT.
• The Company’s successful management of the HEPZATO KIT supply chain, including securing adequate supply of critical components necessary to manufacture and assemble the HEPZATO KIT.
• Successful FDA inspections of the facilities of the Company and those of its third-party suppliers/manufacturers.
• The Company’s successful implementation and management of the HEPZATO KIT Risk Evaluation and Mitigation Strategy.
• The Company’s ability to obtain reimbursement for the HEPZATO KIT.
• The Company’s ability to successfully enter into any necessary purchase and sale agreements with users of the HEPZATO KIT.
• Delays in the presentation of data, or other unforeseen issues relating to the release of clinical trial results.

Future Outlook

Delcath Systems is encouraged by the potential to explore this combination therapy paradigm in other liver-dominant cancers. The company anticipates increased adoption of HEPZATO KIT by treating physicians and patients, driven by these strong clinical results. Delcath is committed to raising awareness of the innovative approach taken in the CHOPIN Trial and accelerating patient referrals to treatment sites.

Management Comments

• "The full publication in The Lancet Oncology validates the impressive efficacy of combining our liver-directed PHP therapy with immune checkpoint inhibition." Gerard Michel, Chief Executive Officer of Delcath Systems.
• "By more than tripling the 1-year progression-free survival rate and nearly doubling the 2-year overall survival, these results strongly underscore the clinical value of this combination and give us even greater confidence in adoption by treating physicians and patients." Gerard Michel, Chief Executive Officer of Delcath Systems.
• "We are also encouraged by the potential to explore this paradigm in other liver-dominant cancers." Gerard Michel, Chief Executive Officer of Delcath Systems.

Industry Context

StockSavvy.ai notes that the publication of these Phase 2 results in a prestigious journal like The Lancet Oncology lends significant credibility to Delcath's combination therapy for metastatic uveal melanoma, a challenging disease with poor outcomes. The demonstrated synergy between liver-directed therapy and immunotherapy could set a new benchmark for treatment strategies in liver-dominant cancers, potentially influencing future clinical guidelines and competitive landscape.

Comparison to Industry Standards

• The safety profile of the combination arm, with 82% Grade 3 or higher adverse events, was similar to that reported in the FOCUS trial (81%), indicating a known and potentially manageable toxicity profile for this type of intensive treatment.
• The significant improvements in progression-free survival (PFS) and overall survival (OS) for metastatic uveal melanoma, a disease with limited effective treatments, position this combination favorably against existing monotherapies or less intensive regimens, potentially establishing a new standard of care.

Stakeholder Impact

• Shareholders: Positive impact due to strong clinical data, potential for increased adoption and market expansion, and validation of the company's technology.
• Patients: Significant benefit for patients with metastatic uveal melanoma, offering a promising new treatment approach with improved survival and response rates.
• Treating Physicians: Provides a new, effective treatment option for a challenging patient population, potentially leading to increased adoption of HEPZATO KIT.

Next Steps

• Delcath Systems plans to raise awareness of the innovative approach taken in the CHOPIN Trial.
• Accelerate the referral of patients to treatment sites.
• Explore the combination therapy paradigm in other liver-dominant cancers.

Key Dates

Recommendation

The publication of highly positive Phase 2 clinical trial results in a prestigious journal like The Lancet Oncology, demonstrating significantly improved progression-free and overall survival rates for metastatic uveal melanoma, provides strong validation for Delcath's core technology and its combination with immunotherapy. This data is likely to drive increased adoption, expand market potential into other liver-dominant cancers, and significantly enhance the company's valuation, making it a strong buy for investors.

Keywords

Delcath Systems, DCTH, CHOPIN trial, metastatic uveal melanoma, mUM, percutaneous hepatic perfusion, PHP, immunotherapy, ipilimumab, nivolumab, melphalan, CHEMOSAT, HEPZATO KIT, liver cancer, oncology, clinical trial results, Lancet Oncology, Phase 2