Even before the American Society of Clinical Oncology (ASCO) freed thousands of abstracts from embargo late Wednesday afternoon, immunotherapy already was emerging as the biggest story at the upcoming meeting in Chicago and big pharma firms as its major stars.

Since being highlighted at last year's ASCO meeting and being named Science magazine's Breakthrough of the Year for 2013, advances in cancer immunotherapy have continued at a frenetic pace, leading with the promising class of immune checkpoint modulators targeting PD-1. Merck & Co. Inc. is expected to score first in the regulatory race, having submitted a biologics license application for its PD-1 inhibitor MK-3475 (pembrolizumab) in melanoma patients unsuccessfully treated with the first melanoma immunotherapy, Yervoy (ipilimumab), and earning priority review, with a PDUFA date of Oct. 28. (See BioWorld Today, Dec. 23, 2013, and May 7, 2014.)

Analysts will be looking to tease out specific efficacy and safety data during Merck's 15 ASCO presentations on MK-3475, among them a late-breaker session June 2 to report data from a 411-patient study in advanced melanoma testing the drug in subjects across all lines of therapy, including those previously given Yervoy.

The Whitehouse Station, N.J.-based firm also is expected to update durability of response and overall survival (OS) data from the longest ongoing MK-3475 melanoma cohort of the KEYNOTE-001 trial. Abstract data released Wednesday (abstract #3005) reported that all patients had at least 13 months or greater of follow-up and, for those with measureable disease, the overall response rate was 41 percent. Median OS was not reached, though the company reported an OS rate at one year of 81 percent.

Merck's MK-3475 filing earlier this month put it ahead of chief competitor Bristol-Myers Squibb Co. in the PD-1 inhibitor arena, at least for treating late-stage melanoma. BMS' nivolumab, however, is the subject of a dozen posters or presentations at ASCO this year, with long-term OS data expected from a monotherapy study in Yervoy-naïve melanoma patients.

Results posted in the abstract (#9002) showed that across the doses tested, nivolumab resulted in two- and three-year OS rates of 48 percent and 41 percent, respectively. Of the 107 patients, 34 had objective responses, with a median response duration of 22.9 months.

But most of the nivolumab presentations will report data from other cancer indications, notably non-small-cell lung cancer, in which data (abstract #8812) showed treatment with nivolumab as a monotherapy in previously treated patients resulted in median OS of 9.2 months to 14.9 months, with one-year and two-year OS rates of 32 percent to 56 percent and 12 percent to 45 percent, respectively. Additional abstracts showed promising OS data in metastatic renal cell cancer, too.

COMBINATIONS COMING UP

Despite Merck's surprising early lead in the PD-1 space, New York-based BMS holds a competitive edge in efforts to combine PD-1 therapy with other cancer drugs. PD-1, or its ligand PDL-1, is expressed on T cells and turns off the T cells, basically telling the immune system not to attack the tumor cells. Blocking PD-1 would turn those T cells back on.

BMS is expected to present data in both RCC and NSCLC at ASCO testing nivolumab in combination with Yervoy, its CTLA-4-targeting molecule. CTLA-4 prevents T cells from being activated in cancer patients.

Interim data from a phase I study in NSCLC (abstract #8023) showed that responses occurred in all four cohorts tested so far, with an overall response rate of 22 percent. Median duration of response has not yet been reached. Safety is continuing to be evaluated, and, according to the abstract, the recommended dose for further testing has not yet been established.

BMS also is testing nivolumab in combination with Sutent (sunitinib, Pfizer Inc.) Tarceva (erlotinib, Roche AG and Astellas Pharma Inc.), with data from both combos expected at ASCO, and disclosed a deal Wednesday to test nivolumab in combination with Celldex Therapeutics Inc.'s CD27-targeting antibody varlilumab in a phase I/II study. (See the story in this issue.)

Of note Wednesday was abstract #3010 showing data from a phase I/II trial testing Yervoy in combination with an IDO-inhibiting drug, INCB024360, from Incyte Corp. Three of eight patients had a confirmed partial response (38 percent), and the 25-mg twice-daily dosing of INCB024360 with Yervoy was generally well tolerated.

Not to be outdone, Merck also has inked deals with the likes of Amgen Inc., Incyte and Pfizer to combine MK-3475 with other cancer drugs. And another player is emerging with Astrazeneca plc, which is testing its CTLA-4-targeted antibody, tremelimumab, with PDL-1 candidate MEDI4736, a drug that has gotten plenty of attention as a single agent. While London-based Astrazeneca is expected to report data from several trials, the only abstract for a tremelimumab/MEDI4736 combo just outlines the design for a phase I trial and offers no data.

BIG PHARMA DOMINATING AGAIN

The buzz around immunotherapy also means that big pharma will be front and center for this year's meeting, just as it was last year, marking a change from only a few years ago when the annual ASCO conference offered a rare chance for small-cap biotechs to shine.

As ISI Group analyst Mark Schoenebaum noted, the ASCO 2014 meeting "is pharma heavy and biotech light," though as consolation he reminded investors that many of the promising drugs in big pharma pipeline originated at biotech – BMS' nivolumab, for instance, was gained by the firm's buyout of Medarex Inc., while Astrazeneca's MEDI4736 was picked up in its acquisition of Medimmune Inc.

But plenty of biotech news will be on hand. A couple of notable presentations at ASCO include MEK inhibitor data from Exelixis Inc. and Array Biopharma Inc.

Exelixis' partner Roche AG is expected to provide updated data from the phase Ib BRIM7 study testing MEK inhibitor cobimetinib with Roche's Zelboraf (vemurafenib) in melanoma patients with BRAF mutations. "These data could read-through to pivotal coBRIM data and a potential [new drug application] filing this year," Piper Jaffray analyst Edward Tenthoff noted in a research report earlier this month.

Array's partner, Novartis AG, meanwhile, is expected to present data on the design of its phase III NEMO study of MEK inhibitor binimetinib in NRAS-mutant melanoma.