Ibrilatazar Plus Chemotherapy Shows Promise in Squamous Cell Lung Cancer

On 7 February 2025, Lung Cancer published a study showing that, in patients with advanced squamous non-small cell lung cancer (NSCLC), ibrilatazar combined with chemotherapy demonstrated "promising efficacy and safety."

What Is Ibrilatazar and How Does It Work?

Ibrilatazar is an autophagy -inducing and cellular stress-activating dual-mechanism drug for killing cancer cells:

• First, it activates cellular pathways called PPARα/γ, increasing the production of a protein called TRIB3. This suppresses the growth-promoting Akt/mTORC1 signaling pathway and induces autophagy, causing cancer cells to digest themselves.
• Second, it increases endoplasmic reticulum stress inside the cell, triggering the "unfolded protein response." This process disrupts cellular repair mechanisms and causes cancer cells to die.

Ibrilatazar is being developed by the Spain-based biotechnology company Ability Pharmaceuticals.

• Related topic: Global Lung Cancer Incidence and Its Distribution by Subtype

A New Contender in the ENDOLUNG Trial

The phase 1/2 ENDOLUNG trial evaluated ibrilatazar combined with paclitaxel and carboplatin in patients with stage III-IV squamous NSCLC who were not candidates for radical radiotherapy.

Patients received ibrilatazar at a starting dose of 1300 mg three times daily until disease progression, unacceptable toxicity, withdrawal of consent or the investigator's decision to discontinue treatment. The dose could be reduced to 1000 mg, 650 mg or 500 mg in the event of dose-limiting toxicity. Patients received carboplatin (AUC, 5) and paclitaxel (175 mg/m2) every 21 days for 8 cycles.

Clinical Results

The objective response rate was 52% among the 25 efficacy-evaluable (EE) patients and 32.5% in the full group of 40 patients. Disease control rates were 84% and 52.5%, respectively.

In both groups, the median duration of response was 5.1 months and median progression-free survival was 6.2 months. Median overall survival was 22.5 months in the EE group and 18.4 months in the full patient group.

Adverse Events

In the full patient group, 97.5% experienced adverse events (AEs) and 55% had grade 3 or higher AEs. Treatment was discontinued because of AEs in 25% of patients. Fatal AEs occurred in 10% of patients, but none of these deaths was attributed to ibrilatazar.

The most common adverse events were fatigue (62.5%), diarrhea (42.5%), nausea (37.5%), anemia (32.5%), alopecia (30.0%), neurotoxicity (27.5%), neutropenia (27.5%), cough (25.0%), loss of taste (25.0%), decreased appetite (25.0%) and vomiting (25.0%).

Conclusion and Next Steps

Ibrilatazar combined with paclitaxel and carboplatin shows a promising efficacy and safety profile in squamous NSCLC. Larger clinical trials are needed to evaluate this combination in broader patient populations and confirm its effectiveness. The trial's importance reflects the need for new and more effective treatments for advanced NSCLC. Future research may build on these promising findings and inform clinical practice.