FDA Clears Phase 1 Study of TGW101 for Advanced Solid Tumor Treatment
Phase 1 trial of TGW101 in advanced solid tumors is enrolling to assess safety and pharmacokinetics and define the maximum tolerated dose in up to 50 patients.
US FDA
- The FDA granted clearance to the investigational new drug (IND) application of TGW101 for the treatment of patients with advanced solid tumors.
- TGW101 is a first-in-class antibody-drug conjugate (ADC) that works to target tumor associated glycoprotein 72 (TAG-72) with a monomethyl auristatin E (MMAE) payload.
- With this clearance, a phase 1 clinical trial plans to evaluate the agent in this patient population.
The FDA cleared the IND application of TGW101, allowing for a phase 1 clinical trial to study the agent in patients with advanced solid tumors.1
TGW101 is being evaluated in an ongoing, open-label, multicenter, phase 1 dose-escalation study for the treatment of patients with advanced solid tumors. The primary end points of the trial are to assess safety, tolerability, and pharmacokinetics, and to establish the maximum tolerated dose, recommended phase 2 dose, and optimal dosing regimen for future study.
The trial is currently enrolling at select sites in the US and aims to recruit up to 50 patients.
Cancer cell: © vitanovski - stock.adobe.com
"TAG-72 is a validated target with overexpression in many high unmet need solid tumors. However, due to its noninternalizing nature, this target has remained unreachable by current ADCs and other therapies which require uptake by tumor cells to activate their antitumor activity. TGW101's highly differentiated profile enables controlled MMAE payload release and activation in the tumor microenvironment without internalization by tumor cells. This controlled drug release is achieved through a click reaction of the ADC linker with a trigger molecule, which is administered in a second step," said Marc Robillard, chief scientific officer and cofounder of Tagworks, in a press release.
"TGW101 has demonstrated a favorable safety profile as well as effective and durable responses in preclinical solid tumor models. The IND clearance and initiation of our phase 1 clinical trial is a significant milestone for our lead program and Tagworks, the pioneer of Click-to-Release chemistry," Robillard continued.
TGW101 is a first-in-class ADC currently under investigation for the treatment of advanced solid tumors. The therapy targets TAG-72, a noninternalizing surface antigen expressed across a range of epithelial-derived malignancies.2
TGW101 is composed of a TAG-72-binding diabody linked to the cytotoxic agent MMAE.1 Unlike traditional ADCs that rely on internalization and lysosomal degradation, TGW101 leverages a novel 2-step mechanism. First, TGW101 is administered via intravenous (IV) infusion and binds to TAG-72 on the surface of tumor cells. Following tumor binding, a small-molecule trigger is delivered IV. This agent selectively cleaves the chemical linker of tumor-bound TGW101, releasing the MMAE payload into the extracellular tumor microenvironment. Further, the MMAE diffuses into nearby tumor cells.
This mechanism allows for targeted delivery of the cytotoxic agent without requiring internalization, potentially enhancing tumor selectivity and limiting off-target toxicity.
"TGW101 represents an attractive new potential treatment option in advanced solid tumors with high unmet need, overcoming certain challenges and limitations of other ADC therapies. TGW101 has the potential to offer an improved antitumor effect and safety profile which may lead to better clinical outcomes. I am excited to collaborate with Tagworks' team to evaluate TGW101 in patients with advanced solid tumors in the phase 1 clinical trial," added Anthony Tolcher, MD, FRCPC, chief executive officer, founder, and director of clinical research of NEXT Oncology San Antonio, and the TGW101 phase 1 primary investigator, in the press release.
