Bristol, Merck, AstraZeneca Bring New 'Checkpoint Inhibitor" Data to ASCO '14
NEW YORK (TheStreet) -- "Immuno-oncology" will be the dominant buzz phrase at this year's American Society of Clinical Oncology (ASCO) annual meeting, just like last year. New classes of drugs designed to dismantle cloaking mechanisms used by cancer cells to hide from a patient's immune system are generating a tremendous amount of excitement in the cancer research community.
Investors are fixated on immuno-oncology drugs, too, with most of the attention being paid to the anti-PD1 and anti-PDL-1 "checkpoint inhibitors" under development by Bristol-Myers Squibb (BMY), Merck (MRK) and Roche (RHHBY). This year marks the ASCO "debut" of AstraZeneca (AZN) to the checkpoint inhibitor race.
Research abstracts were released tonight previewing clinical data to be presented at the ASCO annual meeting, which kicks off on May 31. I've summarized the most relevant checkpoint inhibitor abstracts below. Remember, these results are preliminary. Expect updated data to be presented at the ASCO meeting.
Abstract No. 8023 discloses the first interim, phase I results from the combination of Bristol's experimental checkpoint inhibitor nivolumab with the already approved CTLA-A inhibitor Yervoy (ipilumumab) in patients with first-line non-small cell lung cancer (NSCLC.)Forty-six patients with squamous and non-squamous NSCLC were treated with four different dose regimens of nivo+Yervoy. The overall response rate (confirmed and unconfirmed) was 22%. The confirmed overall response rate was 13%. Another 33% of patients reported stable disease. Grade 3-4 adverse events were reported in 48% of patients and led to treatment discontinuation in 16 patients. Three treatment-related deaths were reported due to respiratory failure, broncho-pulmonary bleeding and toxic epidermal necrolysis. The abstract describes the combination of nivo and Yervoy in lung cancer as "feasible" but says additional dose regiments are being assessed. "The recommended combination dose for phase II/III evaluatin has not been determined." Bristol has already announced plans to file for U.S. approval of nivolumab (monotherapy) for the treatment of third-line squamous cell lung cancer by the end of the year. Abstract No. 8112 is an update of Bristol's ongoing nivolumab monotherapy lung cancer study, which will be used as part of the FDA approval filing. One hundred twenty-nine patients with previously treated lung cancer were administered three different doses of nivolumab. The median overall survival for all patients was 9.9 months. One- and two-year survival rates were 42% and 24%, respectively. The highest-reported median overall survival was 14.9 months for patients treated with 3 mg/kg of nivo. For squamous cell NSCLC patients, the median overall survival was 9.2 months, with one- and two-year survival rates of 40% and 24%, respectively. Grade 3-4 adverse events were reported in 14% of patients. Bristol is also conducting larger phase III studies of nivo in patients with less advanced lung cancer. Switching to Merck but sticking with lung cancer, abstract No. 8007 contains data on the checkpoint inhibitor MK-3475 as initial (first line) therapy in patients with advanced NSCLC. Fifty-seven patients with tumors expressing PD-L1 were treated with three different doses of MK-3475. The preliminary, overall response rate (confirmed and unconfirmed) was 36%. Twenty-five patients, including all but two responders, remain on treatment. A single grade 3 adverse event (pericardial effusion) was reported.
To put these MK-3475 data in perspective, at least year's ASCO meeting, Bristol reported response rates of 30-35% in first-line NSCLC patients treated with nivolumab and doublet chemotherapy. (Thanks to ISI Group analyst Mark Schoenebaum for that reference.) Back to Bristol, abstract No. 4504 is another early study of the nivolumab+Yervoy combination, but this time in metastatic kidney (renal cell) cancer. Forty-four patients with previously untreated and treated kidney cancer (77% had previously therapy) were treated with two dose regimens of nivo+Yervoy. The overall response rates were 29% and 39%. Another 33% and 39% of patients reported stable disease. The duration of response ranged from 4.1 weeks to 22.1 weeks. Grade 3-4 adverse events occurred in 43% of patients. More Bristol data: Abstract No. 9002 is an update of a nivolumab study in heavily pretreated melanoma patients, reporting for the first time, a three-year survival rate of 41%. The previously reported two-year survival rate was 48%. This year's ASCO meeting will be debut of sorts for AstraZeneca's immuno-oncology drug portfolio. Abstract No. 3001 describes a phase I study of AstraZeneca's anti-PD-L1 antibody MEDI4736 ('4736) in patients with advanced (heavily pretreated) solid tumors. Twenty-six patients (13 lung cancer, 8 melanoma, 5 other) were treated with two different dose regimens of '4736. The overall response rate was 15% (three PRs in lung, 1 PR in melanoma.) An additional five patients experienced tumor shrinkage not meeting the definition of partial response. The disease control rate (partial response + stable disease) was 46%. Treatment-related adverse events (all grade 1-2) occurred in 34% of patients, with no patients discontinuing from the study. Abstract No. 3002 reports on expansion of '4736 dosing in additional patients with advanced lung cancer, skin, gastroesophageal, liver, pancreatic, head-and-neck and triple-negative breast cancers. No specific efficact results are noted in the abstract, but it does say, "With a median follow-up of 6 weeks, tumor shrinkage is already detectable in multiple tumor types including pts with melanoma, pancreatic, head and neck, and gastroesophageal cancer."
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