4:07 PM
 | 
Apr 16, 2018
 |  BC Extra  |  Clinical News

Merck rises, BMS falls on PD-1 combo data for NSCLC

Merck & Co. Inc. (NYSE:MRK) and Bristol-Myers Squibb Co. (NYSE:BMY) both reported detailed data Monday from Phase III trials of their anti-PD-1 mAb combos to treat advanced non-small cell lung cancer in the first-line setting.

Merck gained $1.48 to $58.65 after its Keytruda pembrolizumab combo showed an overall survival (OS) benefit in patients with non-squamous disease across three PD-L1 subpopulations. BMS lost $4.57 to $54.08 on data showing that its Opdivo nivolumab plus anti-CTLA-4 mAb Yervoy ipilimumab improved progression-free survival (PFS) in patients with high tumor mutation burden (TMB) across two PD-L1 subgroups.

Both companies presented data at the American Association for Cancer Research meeting in Chicago and published them in the New England Journal of Medicine.

Merck's KEYNOTE-189 trial enrolled 616 non-squamous NSCLC patients regardless of PD-L1 expression, with no EGFR or anaplastic lymphoma kinase (ALK) genomic tumor aberrations and who had not previously received systemic therapy for advanced disease. Keytruda plus Alimta pemetrexed and cisplatin or carboplatin significantly improved OS vs. Alimta plus cisplatin or carboplatin in patients with PD-L1 expression of less than 1% (HR=0.59, 95% CI: 0.38, 0.92), between 1-49% (HR=0.55, 95% CI: 0.34, 0.9) and at least 50% (HR=0.42, 95% CI: 0.26, 0.68). In the overall population, median OS was not reached for the Keytruda combo vs. 11.3 months for Alimta plus cisplatin or carboplatin (HR=0.49, 95% CI: 0.38, 0.64, p<0.00001).

Keytruda plus Alimta and cisplatin or carboplatin also led to a median PFS of 8.8 months and an objective response rate (ORR) of 47.6% vs. 4.9 months (HR=0.52, 95% CI: 0.43, 0.64, p<0.00001) and 18.9% (p<0.00001), respectively, for Alimta plus cisplatin or carboplatin.

In January, Merck said the Keytruda combo met KEYNOTE-189’s co-primary endpoints of improving OS and PFS vs. Alimta plus cisplatin or carboplatin (see BioCentury Extra, Jan. 16).

In the U.S., Keytruda plus Alimta and carboplatin has accelerated approval as first-line treatment of metastatic non-squamous NSCLC.

Merck gained more than $7.5 billion in market cap on April 9 after reporting that Keytruda as monotherapy met the primary endpoint of improving OS in the Phase III KEYNOTE-042 trial as first-line treatment of NSCLC (see BioCentury Extra, April 9).

Loncar Investments’ Brad Loncar recently told BioCentury he believed Merck’s combo would win today’s head-to-head (see BioCentury, April 6).

BMS reported data from 1,739 patients with advanced or recurrent NSCLC in the CheckMate -227 trial showing that Opdivo plus Yervoy improved PFS by 42% vs. platinum-doublet chemotherapy in patients with high TMB, defined as at least 10 mutations/megabase (HR=0.58, 97.5% CI: 0.41, 0.81, p=0.0002). In that population, Opdivo plus Yervoy significantly improved PFS vs. chemotherapy in patients with PD-L1 levels of at least 1% (HR=0.62, 95% CI: 0.44, 0.88) and PD-L1 levels of less than 1% (HR=0.48, 95% CI: 0.27, 0.85).

In patients with high TMB, Opdivo plus Yervoy improved OS by 21% vs. chemotherapy (HR=0.79, 95% CI: 0.56, 1.1). Furthermore in the high TMB subgroup, Opdivo plus Yervoy led to a one-year PFS rate of 43% and an ORR of 45.3% vs. 13% and 26.9%, respectively, for chemotherapy.

In February, BMS said first-line treatment with Opdivo plus Yervoy met the trial’s co-primary endpoint of improving PFS vs. chemotherapy in patients with high TMB -- a change from the original co-primary endpoint of PFS in patients with PD-L1 expression of less than 1%. The second co-primary endpoint, which has not changed, is OS in patients with PD-L1 expression of at least 1% (see BioCentury, Feb. 16).

A BioCentury survey of 5,584 abstracts published ahead of the AACR meeting showed 45 featured TMB, reflecting the attention TMB is gaining as a predictor of response to checkpoint inhibitors following a series of retrospective biomarker studies (see BioCentury, April 12).

Nektar Therapeutics (NASDAQ:NKTR) fell $7.03 to $93.47 on the day's news. Nektar is evaluating its NKTR-214 in combination with Opdivo in select solid tumors. NKTR-214 is an immunostimulatory cytokine engineered to selectively activate IL-2 receptor beta chain (CD122; IL2RB) receptors on cytotoxic T cells, resulting in increased PD-1 expression on T cells and natural killer cells in the tumor microenvironment (see BioCentury, March 2).

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