FDA Grants Fast Track Designation to ALE.C04 in CLDN1+ HNSCC
Investigators will assess the safety and pharmacodynamics of ALE.C04 in patients with CLDN1-positive head and neck squamous cell carcinoma as part of a phase 1/2 clinical trial.
Investigators plan to initiate a first-in-human trial assessing ALE.C04 as a treatment for patients with recurrent or metastatic HNSCC in the second half of 2023.
The FDA has granted fast track designation to the investigational monoclonal antibody ALE.C04 as a treatment for patients with Claudin-1 (CLDN1)–positive head and neck squamous cell carcinoma (HNSCC), according to a press release from Alentis Therapeutics.1
According to preclinical data from an abstract presented at the 2023 American Association for Cancer Research Annual Meeting (AACR), ALE.C04 demonstrated an ability to restore T-cell infiltration and anti-PD1 activity in mouse solid tumors.2 Additionally, investigators indicated that the agent was able to perturb the interface between CLDN1-positive tumor cells and the stroma, which assisted in restoring immune cell infiltration. Overall, investigators reported that non-Junctional CLDN1 may be targetable in solid tumors with ALE.C04 on its own and in combination with anti-PD1 agents.
Investigators plan to initiate a first-in-human trial assessing ALE.C04 as a treatment for patients with recurrent or metastatic HNSCC in the second half of 2023.
“We are excited with this opportunity to expedite the development of ALE.C04 in patients with recurrent or metastatic, CLDN1-positive HNSCC,” Luigi Manenti, MD, chief medical officer at Alentis, said in the press release.“The ongoing phase 1/2 clinical trial in HNSCC will give us important information on ALE.C04’s safety and pharmacodynamic profile as well as its anti-tumor efficacy as monotherapy and in combination with pembrolizumab [Keytruda].”
The first-in-class monoclonal antibody was designed to target CLDN1 expressed in cancer cells by remodeling the extracellular matrix to enable natural killer (NK) cells and T-cell trafficking and by directly attacking tumor cells via the effector function. With this mechanism of action, the treatment may be developed as a monotherapy or in combination with other drugs.
“The FDA’s decision to grant fast track designation underscores ALE.C04’s potential to address a serious unmet medical need in cancer, specifically HNSCC,” Roberto Iacone, MD, chief executive officer at Alentis, said. “We continue to advance our pipeline of antibodies against [CLDN1], an extraordinary target with therapeutic potential across indications in oncology and organ fibrosis.”
The manufacturers of ALE.C04 are also developing an enhanced mechanism of action across several indications as part of a next-generation CLDN1 platform.3 The platform is intended to broaden approaches to restoring the extracellular matrix to advance the efficacy of anti-cancer treatments.
The FDA cleared an investigational new drug (IND) application for ALE.C04 with or without pembrolizumab in the management of HNSCC in June 2023.4
“By targeting exposed CLDN1 on cancer cells, our antibody remodels the extracellular matrix 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,” Manenti said in a press release at the time the FDA cleared the IND for ALE.C04.4 “The high unmet medical need, strong scientific rationale, and our compelling preclinical and translational data makes HNSCC an ideal first indication for ALE.C04 as a monotherapy and in combination with anti-PD-1 treatment.”
References
- 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 24, 2023. https://shorturl.at/nU139
- Toso A, Teixeira G, Zimmermann T, et al. Abstract LB284: CLAUDIN-1 targeting antibody ALE.C04 drives single activity and restores anti-PD1 efficacy in solid tumors. Cancer Res. 2023;83(suppl 8):LB284. doi:10.1158/1538-7445.AM2023-LB284
- Restoring a healthy extracellular matrix can re-sensitize cancer to oncologic therapies and restore tissue and organ function. Alentis Therapeutics. Accessed August 24, 2023. https://shorturl.at/ipFWY
- 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 24, 2023. https://shorturl.at/jqswW
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