HCW on TGTX
1) Physicians highlight tolerability in combination therapies with TGR-1202 and/or TG-1101:
Building on the results we already discussed in the days 1&2 highlights report, TG Therapeutics presented updated data from ongoing trials involving TGR-1202 and TG-1101 (ublituximab), which attracted considerable attention from conference attendees. In a poster presentation, TG provided data for 52 patients in an ongoing Phase 2 trial examining the combination of TGR-1101 with the BTK inhibitor ibrutinib in the treatment of R/R CLL and MCL patients. As expected, the combination was well-tolerated with grade 3 IRR occurring in only 3 patients, none of which required a dose reduction. More importantly, the combination yielded an ORR of 96% in high-risk CLL patients. In our opinion, the impressive response rate to date far out-paces those historically seen with ibrutinib alone (55.9% in R/R CLL with del17p) and could be a key asset to watch as it moves into its planned Phase 3 GENUINE trial, expected to initiate within weeks.
In an oral presentation, the company disclosed preliminary efficacy and safety data from an its ongoing Phase 1/2 dose escalation study of TG-1101 in combination with TGR-1202 in patients with heavily pre-treated R/R B-cell malignancies. In total, the “doublet” combo results included 26 patients with the majority (67%) harboring 17p and/or 11q deletions. Impressively, the doublet therapy generated an ORR of 67% amongst CLL/SLL patients, and halted disease progression in 78% of FL patients. In DLBCL, the combination yielded a 43% ORR, with two confirmed CRs. Critically, the combination continues to demonstrate a favorable safety profile, with no hepatic toxicity observed in any patients treated to date.
Highlighting the benign safety profile of TG-1101 and TGR-1202, early data was presented for a “triplet” combination including TG-1101, TGR-1202, and ibrutinib. A small cohort of five patients was treated with the triplet therapy with no dose reductions or delays necessary in patients for more than four months thus far. Although the data is very preliminary, we are encouraged by the tolerability of the triplet therapy, which has already generated a CR in a MCL patient and a PR in one of two FL patients. In our view, the triplet combination represents a safe and effective alternative to similar combinations targeting both CD20 and PI3K-delta, without exacerbating the unpleasant and potentially dangerous side effects that can come along with ibrutinib, and further dispels concerns of potential antagonism between anti-CD20 antibodies and BTK inhibitors.
