Trial of ARC101 Doses First Patient With CLDN6+ Solid Tumors
ARC101, a potential best-in-class T-cell engager that targets solid tumors expressing CLDN6, is being assessed in a first-in-human trial.
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A first-in-human study (NCT06672185) evaluating ARC101 for the patients with locally advanced or metastatic solid tumors expressing Claudin 6 (CLDN6) has dosed its first patient.1
ARC101, a potential best-in-class T-cell engager, works by targeting solid tumors expressing CLDN6. The agent demonstrates high specificity with no off-target binding. Further, ARC101 avoids other Claudin family proteins, has potent cytotoxicity, a long half-life, and optimal biophysical properties.1
The phase 1 study of ARC101 is currently evaluating its safety, tolerability, pharmacokinetics (PK), pharmacodynamics, optimal dosing, and preliminary antitumor activity in patients with advanced cancer.
"ARC101 is the first program from our growing pipeline to reach the clinic – signifying Third Arc Bio's transition into a clinical stage company," said Peter F. Lebowitz, MD, PhD, chief executive officer and chief medical officer of Third Arc Bio, in a press release. "Given ARC101's remarkable specificity for CLDN6 over other Claudin proteins, we believe ARC101 has the potential to achieve a superior therapeutic index in the clinic.”
In the phase 1 study, ARC101 is being assessed as a monotherapy in patients with locally advanced or metastatic solid tumors expressing CLDN6.2 The dose escalation cohorts are administering ARC101 in escalating doses, with each dose escalation cohort assessing toxicity 21 days after the initial dose. The dose expansion portions are giving patients ARC101 at recommended phase 2 dose(s).
Approximately 70 patients with locally advanced or metastatic solid tumors, including ovarian, testicular, or other CLDN6-positive cancers, will be included in the study. Enrollment is open to those with measurable or evaluable disease, per RECIST v1.1, an ECOG performance status 0 or 1, and adequate organ function.
Patients aged 18 years and older with active CNS involvement, a diagnosis of a malignancy other than the disease under study within 2 years prior to the first dose of study drug, and the presence of uncontrolled ascites will be excluded from the trial. Additional exclusion criteria include having a toxicity related to prior anticancer therapy that has not returned to at least grade 1 in severity or baseline levels, a clinically significant pulmonary compromise, and active autoimmune disease within 12 months prior to first dose of study drug.
The primary end points of the study include frequency and type of dose-limiting toxicities and occurrence and severity of adverse events, serious adverse events and laboratory values. Secondary end points being evaluated are PK, overall response rate, overall survival, duration of response, progression-free survival, and the number of anti-drug antibody–positive patients.
The primary study completion date is currently set for August 1, 2028.
“As we advance the ARC101 clinical program, we are also rapidly progressing our next programs towards the clinic with the execution of critical [investigational new drug]-enabling studies,” added Lebowitz in the press release.
REFERENCES:
Third Arc Bio announces first patient dosed in phase 1 clinical trial of lead T cell engager ARC101 to treat CLDN6 positive cancers. News release. Third Arc Bio Inc. March 13, 2025. Accessed March 14, 2025. https://tinyurl.com/mrxywruc
ARC101 in advanced solid tumors. ClinicalTrials.gov. Updated March 6, 2025. Accessed March 14, 2025. https://www.clinicaltrials.gov/study/NCT06672185?term=ARC101&rank=1
