Preliminary activity in the first in human study of the first-in-class fatty acid synthase (fasn) inhibitor, tvb-2640
Session type: Poster / e-Poster / Silent Theatre session
Theme: Diagnosis and therapy
FASN inhibition is a novel investigational treatment approach that selectively disrupts palmitate biosynthesis, leading to apoptosis in cancer cells. TVB-2640 is an oral, first-in-class, reversible inhibitor of FASN which has demonstrated anti-tumour activity in vivo. Here we present evidence of preliminary efficacy in this first-in-human trial.
In this ongoing multicentre Phase I trial, patients with advanced solid tumours receive oral TVB-2640 (100 mg/m2) once daily as monotherapy, or in combination with weekly IV paclitaxel (80 mg/m2).
The most common AE’s [monotherapy, N=53; combination, N=47] were alopecia (57%), palmar-plantar erythrodysesthesia (PPE) (36%) and dry eye (13%). Gr 3 toxicities included PPE (10%) and corneal oedema (3%); other toxicities were ≤ Gr 2. Toxicities were reversible on dose interruption and TVB-2640 did not enhance paclitaxel toxicity. Five confirmed RECIST partial responses (cPR) and multiple cases of prolonged stable disease (SD) (≥16 weeks) were reported in the combination and monotherapy arms respectively.
Of 21 NSCLC patients, 10 were KRASmut and 8 of these achieved prolonged SD; 3 patients receiving monotherapy (17, 24 and 42 weeks) and 5 patients in the combination arm (23, 30, 83, 95 and 97 weeks). One NSCLC patient (combination) had a cPR at week 12 (remains on study [week 36]).
3/12 breast cancer patients (combination) achieved a cPR; (16 weeks, 2 patients remain on study [week 16 and 24]) and 5 achieved SD (16, 24 weeks, 3 patients remain on study [week 16, 24 and 32]). A patient with peritoneal carcinoma (combination) experienced cPR with a 58% reduction in CA125 levels. Further reductions in CA125 were seen in 5/12 ovarian patients (pre-treated with taxanes and mostly taxane resistant).
TVB-2640 demonstrated prolonged SD in monotherapy and cPR in combination with weekly paclitaxel. Responses were seen in a range of tumour types including KRASmut NSCLC, ovarian and breast cancer.