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

3 comments:

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

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    1. I think that since I can find no report on this trial in ASCO reports this year, that there is nothing new on Clinicaltrials.gov, and that this comment on MPIP in 2015
      (https://www.melanoma.org/find-support/patient-community/mpip-melanoma-patients-information-page/another-choice-trial-stage)
      was OLD news....says it all.

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