AbilityPharma's investigational drug ibrilatazar (ABTL0812) has demonstrated remarkable efficacy in treating squamous non-small cell lung cancer, doubling overall survival in a Phase I/IIa clinical trial recently published in the journal Lung Cancer. The ENDOLUNG trial results represent a significant breakthrough for patients with one of the most challenging lung cancer subtypes.
Trial Design and Patient Population
The ENDOLUNG trial evaluated ibrilatazar in combination with standard chemotherapy (paclitaxel/carboplatin) in 40 patients with stage III/IV squamous non-small cell lung cancer (sq-NSCLC). The study was conducted at six leading oncology hospitals across Spain and France, including the Catalan Institute of Oncology locations in Badalona, Girona and l'Hospitalet, Paoli-Calmettes Institute in Marseille, Virgen del Rocío University Hospital in Seville, and Clinic University Hospital in Valencia.
Efficacy Results Show Dramatic Improvements
The combination therapy demonstrated substantial improvements across all efficacy endpoints when compared to historical controls. Most notably, median overall survival increased from 12.3 months to 22.5 months (95% CI 10.4-ND), effectively doubling patient survival time.
Additional efficacy improvements included an overall response rate of 52% versus 31.7% in historical controls, representing a 40% increase. Median progression-free survival reached 6.2 months (95% CI: 4.4-8.8) compared to 4.2 months in historical controls, a 44% improvement.
Novel Mechanism of Action
Ibrilatazar represents a new class of autophagy-mediated oncology drugs that selectively target cancer cells while sparing normal cells. The drug works by targeting the PI3K pathway and autophagy mechanisms, offering a different approach to treating this challenging cancer subtype.
Dr. Joaquim Bosch, medical oncologist from ICO Girona and first author of the publication, emphasized the significance of this novel approach: "Squamous cell lung cancer is one of the lung cancer subtypes with the fewest therapeutic options and the poorest prognosis. That's why it is especially relevant that a new molecule like ibrilatazar, with a different mechanism of action, has shown promising antitumor activity."
Safety Profile and Tolerability
The combination of ibrilatazar plus paclitaxel/carboplatin exhibited a favorable safety profile. The addition of ibrilatazar to standard chemotherapy did not introduce additional significant adverse events beyond those associated with paclitaxel/carboplatin alone, aligning with historical control safety data.
Pharmacokinetic analysis showed that ibrilatazar's parameters aligned with target engagement observed in preclinical studies, and blood pharmacodynamic biomarkers indicated sustained target regulation for at least 28 days following treatment initiation.
Clinical Significance and Future Directions
Dr. Teresa Morán, medical oncologist at ICO Badalona and senior author on the publication, highlighted the clinical potential: "Ibrilatazar, when administered in combination with chemotherapy and subsequently as maintenance therapy, has shown a median overall survival of over 22 months in sq-NSCLC. These results are highly promising. If confirmed in a randomized study, ibrilatazar could become a treatment option for this complex disease."
The results address a significant unmet medical need in squamous non-small cell lung cancer, which has historically had limited therapeutic options and poor outcomes. Dr. Carles Domènech, AbilityPharma's CEO & Co-Founder, described the publication as "a crucial development in the study of new drugs and combinations for advanced squamous lung cancer" and "a significant milestone in our mission to deliver transformative treatments to cancer patients."
The findings build upon AbilityPharma's previous research published in the International Journal of Cancer, further establishing the company's position in developing autophagy-mediated oncology therapies. The promising Phase I/IIa results support advancing ibrilatazar as a potential backbone therapy for patients with this common lung cancer subtype worldwide.
