FDA Grants Fast Track Status to ALE.C04 for Recurrent or Metastatic CLDN1+ HNSCC

The FDA has granted fast track designation to ALE.C04 for use as a potential therapeutic option in patients with recurrent or metastatic, Claudin-1 (CLDN1)–positive head and neck squamous cell carcinomas (HNSCC).¹

The first-in-class monoclonal antibody was designed with an effector function that directly targets the cancer, silences carcinogenic signaling that is mediated by CLDN1, and opens the extracellular matrix (ECM).² It is known that CLDN1 expression is upregulated and exposed in disease pathogenesis.³ ALE.C04 targets exposed non-junctional CLDN1, reverts pathogenesis linked with ECM remodeling and fibrosis, and sensitizes tumors to treatment.

“The FDA’s decision to grant fast track designation underscores ALE.C04’s potential to address a serious unmet need in cancer, specifically HNSCC,” Roberto Iacone, MD, chief executive officer of Alentis Therapeutics, stated in a press release.¹ “We continue to advance our pipeline of antibodies against CLDN1, an extraordinary target with therapeutic potential across indications in oncology and organ fibrosis.”

Preclinical data presented at the 2023 AACR Annual Meeting showed that ALE.C04 inhibits tumor growth in several CDX and PDX in vivo tumor models.⁴ Investigators also found that in mouse tumor cells, CLDN1 overexpression correlated with T-cell exclusion and resistance to checkpoint inhibition. ALE.C04 restored the efficacy of PD-1 treatment and T-cell infiltration.

Moreover, the agent was found to disrupt the interface between CLDN1 expression on tumor cells and the stroma, which resulted in the restoration of immune cell infiltration. It was concluded that the agent can have activity as a monotherapy and in combination with a PD-1 inhibitor.⁴

To this end, in June 2023, Alentis Therapeutics announced that the FDA greenlit an investigational new drug application to examine ALE.C04 as a single agent and in combination with pembrolizumab (Keytruda) in patients with recurrent or metastatic HNSCC as part of a first-in-human clinical trial.⁵ The trial is expected to launch in the second half of 2023.

“With ALE.C04, we aim to treat solid tumors in a unique way. By targeting exposed CLDN1 on cancer cells, our antibody remodels the ECM favoring T- and NK-cell trafficking, which in turn directly kills CLDN1-positive tumor cells and breaks the checkpoint inhibitor resistance in immune-excluded tumors,” Luigi Manenti, MD, chief medical officer of Alentis Therapeutics, stated in an earlier press release.⁵ “The high unmet medical need, strong scientific rationale, and our compelling preclinical and translational data make HNSCC an ideal first indication for ALE.C04 as a monotherapy and in combination with anti–PD-1 treatment.”

In the most recent news announcement, Manenti noted that the trial seeks to shed light on the safety and pharmacodynamic profile of ALE.C04, and its efficacy as a single agent or in combination with immunotherapy.¹

References

1. Alentis Therapeutics receives FDA fast track designation for ALE.C04 for the treatment of Claudin-1 positive HNSCC. News release. Alentis Therapeutics. August 24, 2023. Accessed August 25, 2023. https://alentis.ch/alentis-therapeutics-receives-fda-fast-track-designation-for-ale-c04-for-the-treatment-of-claudin-1-positive-hnscc/
2. Alentis’ unique CLDN1 monoclonal antibodies can revert the extracellular matrix to its healthy state in cancers and organ tissues. Alentis Therapeutics website. Accessed August 25, 2023. https://alentis.ch/pipeline-2/
3. Targeting CLDN1 to treat cancer and fibrosis. Alentis Therapeutics website. Accessed August 25, 2023. https://alentis.ch/cldn1/
4. Toso A, Teixeira G, Zimmermann T, et al. Abstract LB284: CLAUDIN-1 targeting antibody ALE.C04 drives single activity and restores anti-CD1 efficacy in solid tumors. Cancer Res. 2023;83(suppl 8):LB284. doi:10.1158/1538-7445.AM2023-LB284
5. Alentis Therapeutics receives IND clearance from FDA for ALE.C04 for the treatment of CLDN1+ tumors. News release. Alentis Therapeutics. June 14, 2023. Accessed August 25, 2023. https://alentis.ch/alentis-therapeutics-receives-ind-clearance-from-fda-for-ale-c04-for-the-treatment-of-cldn1-tumors/