Friday, June 9, 2017

ASCO 2017: Anti-LAG-3 plus nivo, for melanoma already treated with anti-PD-1/PD-L1

Here is what I have on LAG-3:
2014:  How to make anti-PD1 work better with a new player...LAG-3????
2016:  The Future for Melanoma Treatment = Combo's! Dr. Weber breaks it down -

Now, there's this ~ anti-LAG-3 with Nivo:

Initial efficacy of anti-lymphocyte activation gene-3 (anti–LAG-3; BMS-986016) in combination with nivolumab (nivo) in pts with melanoma (MEL) previously treated with anti–PD-1/PD-L1 therapy.
ASCO 2017. J Clin Oncol 35, 2017. Ascierto, Melero, Bhatia, et al.

Background: Signaling via LAG-3 and other T-cell inhibitory receptors (eg, PD-1) can lead to T-cell dysfunction and tumor immune escape. Simultaneous blockade of LAG-3 + PD-1 may synergistically restore T-cell activation and enhance antitumor immunity. In a phase 1/2a study, BMS-986016 (IgG4 mAb targeting LAG-3) ± nivo (IgG4 mAb targeting PD-1) demonstrated tolerability, peripheral T-cell activation, and preliminary clinical activity. Here we describe preliminary efficacy of BMS-986016 + nivo in pts with MEL whose disease progressed on/after prior anti–PD-1/PD-L1 therapy, along with updated safety from all dose expansion pts. Methods: Pts with MEL must have had prior anti–PD-1/PD-L1 (± anti–CTLA-4 or BRAF/MEK inhibitors) and progressive disease (PD). Pts received BMS-986016 80 mg + nivo 240 mg IV Q2W. Primary objectives were safety and objective response rate (ORR; complete [CR] + partial [PR] response), disease control rate (DCR; CR + uCR + PR + uPR + stable disease [SD] greater than 12 wk), and duration of response. Results: At data cutoff, 43 pts with MEL had been treated with BMS-986016 + nivo following PD on/after prior anti–PD-1/PD-L1 with known prior best responses of 1 CR, 9 PR, 12 SD, and 16 PD. Of the 43 pts, 30 (70%) also had prior anti–CTLA-4, 20 (47%) had greater than/ = to 3 prior therapies, and 15 (35%) had BRAFmutationsIn the 31 efficacy-evaluable pts to date, ORR was 16% (confirmed/unconfirmed) and DCR was 45% with benefit observed even in some pts refractory to prior anti–PD-1. Evaluations are ongoing for most pts, with median treatment duration of 10 wk for all 43 pts.  Any grade and grade 3/4 treatment-related AEs occurred in 46% and 9%, respectively, across all dose expansion pts (n = 129). Conclusion: Addition of BMS-986016 to nivolumab demonstrates encouraging initial efficacy in pts with MEL whose disease progressed on/after prior anti–PD-1/PD-L1 therapy, and a safety profile similar to nivolumab monotherapy. Clinical trial information: NCT01968109

43 melanoma patients with progression on or after treatment with anti-PD-1 or anti-PD-L1, 30 of whom had also been previously treated with ipi - were treated with nivo and BMS-986016 (anti-LAG-3).  In the end, 31 patients were evaluated.  ORR = 16%.  DCR (disease control rate) = 45% "with benefit observed even in some patients refractory to prior anti-PD-1".  Median treatment duration = 10 weeks. 

Small numbers. Patients who had already been through a lot.  Fingers crossed. - c


  1. Hi, how do you comment polynoma POL-103A which is under 3rd-stage clinical trial?

    1. I think that since I can find no report on this trial in ASCO reports this year, that there is nothing new on, and that this comment on MPIP in 2015
      was OLD news....says it all.