* Combination of durva/treme fails to beat chemotherapy
* Durva on its own also misses in MYSTIC immunotherapy study
* Study marked AstraZeneca's big bet on new cancer field
* CEO declines to comment on rumours he might join Teva (Adds banking sources on takeover speculation, more reaction)
LONDON, July 27 (Reuters) - AstraZeneca's combination of two injectable immunotherapy drugs failed to help patients as hoped in a closely watched advanced lung cancer trial, sending its shares plunging on Thursday.
The so-called MYSTIC study was the most anticipated clinical experiment in the pharmaceutical industry this year and the news saw the shares tumble 16 percent, wiping some $14 billion off the company's value in their biggest ever daily fall.
The study was seen as key to proving the value of the group's new drug pipeline and its future as an independent company, after it spurned a $118 billion takeover attempt by Pfizer in 2014.
Some analysts said investors would now focus on whether AstraZeneca will become a target again, although banking sources said Pfizer was unlikely to return and others, including Novartis, might be deterred by the weak growth outlook.
AstraZeneca Chief Executive Pascal Soriot told reporters he did not believe the group was now more vulnerable, noting that positive data could have actually made it more desirable.
Initial results from MYSTIC found the combination of durvalumab and tremelimumab was no more effective at stopping disease progression than chemotherapy in patients expressing a protein called PD-L1 on 25 percent or more of their cancer cells.
Immunotherapy drugs are designed to help the body's immune cells kill cancer and PD-L1 levels are widely used as a benchmark to determine if they are likely to work for individual patients.
As a secondary endpoint, although not formally tested, durvalumab monotherapy also would not have met a pre-specified threshold of progression-free survival benefit, the company added. Durvalumab is already on the market for bladder cancer, under the brand name Imfinzi.
Despite the negative initial results on disease progression from the MYSTIC trial, Soriot said there was still a chance the treatment might show a benefit when overall survival data becomes available in 2018. Uncertainty about the MYSTIC outcome had been heightened recently by speculation that Soriot might be considering a highly paid new job as head of Israel-based Teva Pharmaceutical Industries.
Soriot declined to comment directly on what he described as "rumours" on Thursday, although company insiders said he would have had to make a statement if he had firm plans to leave.
"I'm not a quitter," Soriot said. "Im proud to be the CEO of this company and I look forward to continuing on our journey ahead and continuing to lead the incredible team ... the only thing I can tell you is I am here today."
GOOD NEWS FOR MERCK?
Immunotherapies promise to revolutionise cancer care, prompting a race among companies to develop rival treatments.
Lung cancer is the single biggest market opportunity and Jefferies analyst Jeffrey Holford said the MYSTIC setback removed around 10 to 15 percent of mid-term earnings potential.
AstraZeneca's pain is likely to be good news for Merck & Co , the only manufacturer on the market today with an immunotherapy treatment for previously untreated lung cancer.
But Bristol-Myers Squibb, which is working on a similar combination to AstraZeneca's durva/treme cocktail, could be hit, according to Bernstein analyst Tim Anderson.
AstraZeneca - a relative latecomer in immunotherapy - had been hoping to secure a substantial slice of a multibillion-dollar market by proving its combination could help previously untreated patients with advanced lung cancer.
It has already shown in a separate trial called PACIFIC that durvalumab alone can help some patients with earlier-stage disease.
Durvalumab, which AstraZeneca flagged in 2014 as having annual sales potential of $6.5 billion, is key to its drive into oncology.
Offsetting the MYSTIC hit, the company announced that Tagrisso significantly improved progression-free survival in another lung cancer trial called FLAURA. Soriot said this put it on track for eventual sales of more than $4 billion a year.
AstraZeneca has also established a strategic oncology collaboration with Merck to study cancer drug combinations using its drug Lynparza, which is already approved for ovarian cancer but could have much wider uses when combined with immunotherapy.
Merck will pay AstraZeneca up to $8.5 billion under the deal, in exchange for half of future Lynparza sales, including $1 billion this year.
"AstraZeneca is currently at a crossroads," said Joe Walters, senior fund manager at Royal London Asset Management, a top-30 shareholder, according to Thomson Reuters data.
"In our view, the group should make every effort to capitalise on their strategic tie-up with Merck announced today and strong progress in the trials for Tagrisso."
The news came as AstraZeneca reported drug sales fell again in the second quarter, hit by loss of patents on blockbusters like cholesterol pill Crestor.
Despite income from disposals and external deals, first-quarter revenue fell 10 percent in dollar terms to $5.05 billion, while core earnings per share (EPS) rose 5 percent to $87 cents.
Industry analysts, on average, had forecast revenue of $5.0 billion and earnings of 80 cents, according to Thomson Reuters data.
AstraZeneca reiterated its outlook for the full year that revenue would decline at a low to mid single-digit percentage rate, with core EPS dropping by a low to mid-teens percentage.
(Additional reporting by Pamela Barbaglia and Simon Jessop; Editing by Keith Weir)