From The Life Sciences Report then -- an interview transcript bit -- do go read it all:
. . . .TLSR: What is going on with Bristol-Myers Squibb? Wall Street thought this company would be first to market in the PD-1 space.
SD: Bristol-Myers Squibb's nivolumab (BMS-936558) is a humanized monoclonal IgG4 antibody directed against PD-1, and was seen as the frontrunner before Merck leapfrogged Bristol to be first in line for approval at the FDA in Yervoy-failure melanoma patients.
Bristol-Myers is going after third-line squamous cell non-small cell lung cancer using nivolumab monotherapy. The company intends to file its BLA with the FDA by year-end. Bristol's abstract #8112 shows data that will be part of the FDA filing, in which 129 patients treated with nivolumab alone had overall survival of 9.9 months across three different dosing regimens. The best results were in the 37 patients receiving the 3mg/kg, mid-range dose, with an overall survival of 14.9 months.
Also of interest is abstract #8023, which shows Phase 1 interim results using nivolumab and Yervoy, the approved melanoma drug, as first-line treatment in squamous and non-squamous cell non-small cell lung cancer patients (using four dosing regimens). The combination showed an objective response rate of 22% (pooled confirmed and unconfirmed), with the best results using N3+I1 milligrams per kilogram (mg/kg) dosing (3mg/kg of nivolumab + 1mg/kg of ipilimumab) in squamous cell, with a pooled objective response rate of 63%. An odd result is that in 29 evaluable tumor samples, the objective response rate did not correlate with the PD-L1 biomarker.
A trial of 44 metastatic renal cell carcinoma patients, 77% previously treated, was described in abstract #4504. The nivolumab + Yervoy combination yielded objective response rates of 29% at N3+I1mg/kg dosing, and 39% in N1+I3mg/kg dosing. In these patients, it appears that the less nivolumab administered, the better the results.
Long-term follow-up data for 107 treatment-failure metastatic melanoma patients that were never treated with Yervoy showed three-year overall survival at 41% in abstract #9002. The one-year and two-year survival rates were 63% and 48%, so the results appear fairly durable.
In total, Bristol-Myers will have six oral presentations on nivolumab data at ASCO, including presentations on melanoma, non-small cell lung cancer and renal cell carcinoma in combination with Yervoy. The company is hedging its bets in a collaboration with Celldex Therapeutics (CLDX:NASDAQ), using nivolumab + varlilumab, an anti-CD27 monoclonal antibody, in a Phase 1/2 trial in multiple tumor types, including non-small cell lung cancer, metastatic melanoma, ovarian, colorectal and squamous cell head-and-neck cancers. The trials are to be conducted by Celldex. . . .
[What about Merck's pembrolizumab?]
Merck's MK-3475 has 15 abstracts and six oral presentations at ASCO, with data for multiple indications. The most significant ASCO data for Merck was not released with the rest of the abstracts, but will be presented on June 2 as part of a late-breaking abstract session (abstract #LBA9000). The company will reveal the data on 411 advanced melanoma patients across the entire therapy spectrum, including Yervoy-failure patients, which is part of Merck's current FDA biologics license application (BLA).
Additional evidence that MK-3475 is effective in melanoma, and that PD-1/PD-L1 receptors may be used as biomarkers, is in abstract #3005. In 135 melanoma patients treated with MK-3475, objective responses were seen as late as 64 weeks, with some conversions to complete response as late as 72 weeks. The overall response rate was 41%. The median overall survival had not yet been reached, but the one-year survival rate for PD-L1-positive patients was 84%, and 69% in PD-L1-negative patients. However, abstract #3015 showed that baseline tumor size was the strongest independent prognostic factor in patients with metastatic melanoma treated with MK-3475.
The early non-small cell lung cancer data, contained in abstract #8007, showed that in a Phase 1 trial using MK-3475 monotherapy as first-line therapy in locally advanced or metastatic non-small cell lung cancer, the 45 patients treated had an objective response rate of 36% (pooled confirmed and unconfirmed). While the compound appears effective, it may best be used in a combination therapy in this setting.
. . .Merck strongly believes MK-3475 is an entirely new oncology platform. The company is proceeding at full speed, with two dozen clinical trials in 30 different tumor types ongoing during 2014. Seven of these are late-stage Phase 3 clinical trials, including trials in advanced melanoma, advanced non-small cell lung cancer, advanced head-and-neck cancer and advanced bladder cancer.
Merck is also doing multiple combination therapy collaborations with MK-3475, including with Pfizer Inc.'s (PFE:NYSE) axitinib and PF-2566, Incyte Corp.'s (INCY:NASDAQ) INCB24360, and Amgen Inc.'s (AMGN:NASDAQ) T-Vec (talimogene laherparepvec). . . .
Do stay tuned today and tonight -- through to Monday night. Much more to come.
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