CatalYm Reports Durable Complete Responses in Late-Stage NSCLC, Urothelial, and Hepatocellular Cancer with Visugromab/Nivolumab

CatalYm has recently announced promising follow-up results from its ongoing “GDFATHER” Phase 1/2a trial, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024 in Chicago. The trial investigates the efficacy of their lead candidate, visugromab, combined with the anti-PD-1 antibody nivolumab, in patients with relapsed or refractory non-small cell lung cancer (NSCLC), urothelial cancer (UC), and hepatocellular carcinoma (HCC). This combination demonstrates significant anti-tumoral activity and excellent safety in heavily pretreated patients.

The trial data were shared by Prof. Ignacio Melero, MD, PhD, of the Universidad de Navarra, who highlighted the potential of visugromab to enhance clinical response and durability in advanced metastatic tumors. CatalYm’s Chief Medical Officer, Dr. Eugen Leo, emphasized the significant long-term tumor control observed with visugromab, which other cancer immunotherapies have failed to achieve.

Key Clinical Findings:

Objective Response Rates (ORR):
- Non-squamous NSCLC: 19.0% (4/21), with 2 partial responses (PR) and 2 complete responses (CR).
- UC: 19.2% (5/26), with 4 PRs and 1 CR.
- HCC: 20.0% (4/20), with 3 PRs and 1 CR in early readouts.

Duration of Response (DoR):
- NSCLC and UC: Mean DoR exceeded 15 and 14 months, respectively, with 77% of responses ongoing.
- HCC: Data still maturing with 12 patients continuing on treatment.

Overall, an ORR of 16.7% was observed across 90 patients in various cohorts. Notably, 53.3% of responders achieved a depth of response (PR or CR) not seen with prior checkpoint inhibitor (CPI) therapy. Among the complete responders, three out of four had not experienced CR with any prior treatments.

Safety and Tolerability:
The combination of visugromab and nivolumab showcased high tolerability, with most treatment-emergent adverse events (TEAEs) being mild to moderate. Only 8.1% of patients experienced severe TEAEs (Grade ≥ 3).

Mechanism and Biomarker Analysis:
Patient sample analyses suggest that GDF-15, a tumor-produced immunosuppressant, plays a significant role in immune resistance. Elevated serum levels of GDF-15 correlated inversely with intratumoral T cell numbers and their proliferation. Visugromab, by neutralizing GDF-15, led to increased serum interferon-γ levels and chemokines CXCL9 and CXCL10, essential for stimulating immune responses in NSCLC and UC patients.

Preclinical studies further supported the role of GDF-15 in developing resistance to standard cancer therapies, such as platinum-based chemotherapies and CPI treatments. CatalYm is therefore planning a broad Phase 2b program to explore visugromab’s impact in first- and second-line settings where these regimens are standard.

Future Directions:
CatalYm’s CEO, Phil L’Huillier, expressed confidence in visugromab’s potential to overcome cancer therapy resistance. The company aims to initiate randomized, controlled studies in major cancer indications in 2025, focusing on combining visugromab with standard treatments to further enhance patient outcomes.

GDFATHER-2 Trial:
The Phase 2a segment of the GDFATHER-2 trial, initiated in March 2022, involves multiple cohorts and plans to enroll over 200 patients. The trial includes extensive biomarker evaluations to identify potential responders and refine treatment approaches.

About Visugromab:
Visugromab is a monoclonal antibody targeting GDF-15, which cancer cells use to evade immune attacks. By neutralizing GDF-15, visugromab reinstates immune cell activation and tumor infiltration, showing durable anti-tumor efficacy when combined with anti-PD-1 treatments.

CatalYm is advancing visugromab to Phase 2b studies, aiming to establish it as a new class of cancer immunotherapy across various regimens, potentially setting a new standard in cancer care.

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