FDA Elevates Novel Targeted Therapies in Solid Tumors


Novel agents are now under development for newly druggable targets in patients with solid tumors.

The FDA has been busy adding designations for potentially impactful drugs that were previously granted investigational new drug applications for the treatment of patients with solid tumors.1,2 Biomarkers like Claudin-1 and MUC-1 are now proven to be druggable targets in cancer,3,4 and first-in-human studies are being designed to investigate the efficacy and safety for therapies targeting these important biomarkers.1,2

Targeting Claundin-1

The FDA has granted fast track designation to ALE.C04 for the treatment of patients with recurrent or metastatic, Claudin-1 (CLDN1)-positive head and neck squamous cell carcinoma (HNSCC).1

“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,” said Roberto Iacone, MD, chief executive officer of Alentis, in a press release. “We continue to advance our pipeline of antibodies against Claudin-1, an extraordinary target with therapeutic potential across indications in oncology and organ fibrosis.”

ALE-C04 is a monoclonal antibody that is first in its class and has a high specificity for targeting CLDN1, according to the developer, Alentis Therapeutics. In a preclinical study, ALE-C04 demonstrated ability to drive anti-tumor efficacy in mouse solid tumor cells when used alone or in combination with an anti-PD-1 therapy.5

The agent will soon be investigated in a first-in-human study.

DNA structure on science background | Image Credit: © Crystal light - www.stock.adobe.com

DNA - Image Credit: © Crystal light - www.stock.adobe.com

“We are excited with this opportunity to expedite the development of ALE.C04 in patients with recurrent or metastatic, CLDN1-positive HNSCC. 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],” said Luigi Manenti, MD, chief medical officer of Alentis, in the press release.

Targeting MUC1

The FDA also granted an orphan drug designation to Mab-AR20.5 for the treatment of patients with pancreatic cancer.2

According to the developer, CanariaBio Inc, Mab-AR20.5 is an IgG1k type murine monoclonal antibody. Preclinical research for the agent shows that Mab-AR20.5 had MUC1-specific immune responses that reject pancreatic tumors. Moreover, Mab-AR20.5 demonstrated the ability to improve survival in this patient population.6

"Receiving orphan drug designation for MAb-AR20.5 is a significant milestone for CanariaBio Inc. and speaks to the potential promise of this novel therapeutic approach," said Mike Na, the chief executive officer of CanariaBio Inc, in a press release. "We are deeply committed to advancing innovative treatments for patients with pancreatic cancer and remain hopeful that MAb-AR20.5 will offer a new lifeline for those affected."


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 24, 2023. https://tinyurl.com/5fw392fc

2. CanariaBio achieves significant milestone with FDA's orphan drug designation for MAb-AR20.5 targeting pancreatic cancer. News release.

3. Toso A, Teixeira G, Zimmermann T, et al. CLAUDIN-1 targeting antibodies in solid tumors: From ALE.C04 to CLAUDIN-1 oncology platform. Immuno-Oncology and Technology. 2022;16(suppl 1). Doi: 10.1016/j.iotech.2022.100305

4. Panchamoorthy G, Gin C, Raina D, et al. Targeting the human MUC1-C oncoprotein with an antibody-drug conjugate. JCI Insight. 2018;21;3(12):e99880. doi: 10.1172/jci.insight.99880.

5. 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. Clin Can Res. 2023;83(suppl 8: LB284. doi: 10.1158/1538-7445.AM2023-LB284

6. Mehla K, Tremayne J, Grnukemeyer JA, et al. Combination of mAb-AR20.5, anti-PD-L1 and PolyICLC inhibits tumor progression and prolongs survival of MUC1.Tg mice challenged with pancreatic tumors. Cancer Immunol Immunother. 2018;67(3):445-457. doi: 10.1007/s00262-017-2095-7.

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