Genentech takes on BMS, Merck with positive I/O lung cancer PhIII data

Roche’s Genentech ($RHHBY) has rolled out positive Phase III data for its cornerstone immunotherapy treatment Tecentriq in second-line, non-small cell lung cancer (NSCLC). The news comes shortly after Bristol-Myers Squibb ($BMY) reported a Phase III miss last month for its Opdivo in first-line NSCLC, on the heels of strong positive data for Merck’s ($MRK) Keytruda in that indication.

Tecentriq (atezolizumab) has an Oct. 19 review date in NSCLC under a priority review with the FDA. In May, it was the first PD-L1 inhibitor to be approved by the FDA--to treat a type of bladder cancer. This time it’s up for review specifically to treat NSCLC patients whose disease has progressed during or after platinum-based chemotherapy and for those with an EGFR mutation-positive or ALK-positive tumor; the agency has also granted the drug breakthrough therapy designation in that indication.

The drug has been singled out as a "cornerstone" of Roche’s cancer immunotherapy strategy; it, like that of every other big pharma in immuno-oncology, is focused on finding advantageous combinations that will boost the efficacy of checkpoint inhibitors targeting PD-1 and PD-L1. In May, it did a deal with CAR-T (chimeric antigen-receptor T-cell) developer Kite Pharma ($KITE) to test Tecentriq alongside Kite's KTE-C19 in patients with refractory, aggressive non-Hodgkin lymphoma (NHL).

Including Tecentriq, Roche has at least 10 oncology immunotherapy molecules that are clinical stage or later--with a total of 20 under investigation, the biopharma said in June on an American Society of Clinical Oncology (ASCO) conference call summing up its oncology strategy.

It’s aiming for three immuno-oncology categories: to activate or prime the front end of the immune system, to take the breaks off the immune system and to bypass the normal immune system. Although approved immunotherapy treatments offer major advances over prior treatment approaches, they don’t work for most patients. That’s where the combinations are slated to come in--but biopharmas are now pursuing all sorts of angles on this front, many of which are unlikely to pan out in the clinic.

“The way to get to the 70% to 80% of the patients that are not responding to single-agent immunotherapy is through scientifically rationally based combinations,” said Roche CEO Daniel O’Day on the June ASCO call. “Since we sat here last year, we more than doubled the number of combinations that we have. We have more than 50 trials going on. More than 30 of those are combination trials and that number is already outdated as we speak.”

The latest Tecentriq data show that it met the overall survival primary endpoints in both the overall population and in a sub-group who express PD-L1. The trial was versus docetaxel in patients with locally advanced or metastatic NSCLC whose disease progressed on or after treatment with platinum-containing chemotherapy.

The 1,225-patient OAK study randomized participants 1:1 to either docetaxel or Tecentriq infusions every three weeks. This analysis was based on the first 850 patients. The trial includes secondary endpoints of objective response rate (ORR), progression-free survival (PFS), duration of response (DOR) and safety, which will be analyzed when the full data set is available.

Genentech said it expected to present the full results at an undisclosed medical meeting later this year.

Competitor Bristol-Myers saw its Opdivo, an approved PD-1 inhibitor, recently fail a Phase III trial in first-line NSCLC, after Merck had reported strong positive data for its Keytruda first-line advanced NSCLC in June. Both are already FDA-approved for second-line use, but Tecentriq could offer a challenge on that front.

“If approved with a broad label similar to Opdivo, Tecentriq will narrow Opdivo’s marketing advantage in PD-L1-unselected patients,” suggested Leerink analyst Seamus Fernandez in a Sept. 1 note. “While Roche may attempt to market Tecentriq as having a safety advantage as a PD-L1 inhibitor, full data from the OAK trial will be necessary to assess any true differentiation on either safety or efficacy. Broadly speaking, we continue to view the approved PD-1 and PD-L1 inhibitors as having modest differences in efficacy and safety profiles, with the biggest differentiation derived from labeled indications.”

He concluded, “That said, OAK's success in the broad second-line patient group following soon after BMY's failed CM-026 trial is likely to increase the commercial challenges to BMY's current leadership position.”