GITR agonistic antibodies are expected to increase the antitumor response mainly by reducing the effect of Foxp3+ T regulatory cells. TRX-518 is a novel GITR agonist that has shown good pharmacodynamic activity by depleting T regs in preclinical models, with limited clinical activity demonstrated in patients with advanced solid tumors.

3 years ago

Journal

FOXP3 (Forkhead Box P3)

TRX-518

over3years

Phase IB Study of GITR Agonist Antibody TRX518 Singly and in Combination with Gemcitabine, Pembrolizumab or Nivolumab in Patients with Advanced Solid Tumors. (PubMed, Clin Cancer Res)

TRX518 showed an acceptable safety profile with pharmacodynamic activity. Repeated dose TRX518 monotherapy and in combination resulted in limited clinical responses associated with immune activation.

over 3 years ago

P1 data • Journal • Combination therapy

CD8 (cluster of differentiation 8) • TNFA (Tumor Necrosis Factor-Alpha)

Keytruda (pembrolizumab) • Opdivo (nivolumab) • gemcitabine • TRX-518

5years

A Dose Escalation and Expansion Study of TRX518 in Combination With Cyclophosphamide Plus Avelumab in Advanced Solid Tumors (clinicaltrials.gov)

P1/2, N=10, Terminated, Leap Therapeutics, Inc. | N=125 --> 10 | Trial completion date: Sep 2021 --> Jul 2020 | Active, not recruiting --> Terminated | Trial primary completion date: Jun 2021 --> Jul 2020; Product development discontinued unrelated to safety.

5 years ago

Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)

HR positive • HER-2 negative

Bavencio (avelumab) • TRX-518 • cyclophosphamide intravenous