Roche's Tecentriq-based melanoma combos leapfrog into pivotal trials after promising PhIb results

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Cheered by “extraordinarily high” efficacy in chemo-free combo studies, Roche is powering into late-stage trials with two different melanoma-fighting cocktails based on its brand-new immunotherapy Tecentriq.

It’s just one piece of an immunotherapy combo puzzle that Roche is assembling, with more than three dozen trials testing various combinations of oncology meds, including Tecentriq and other targeted therapies in its stable.

The company is counting on its melanoma franchise, much smaller than its blockbuster breast cancer meds at the moment, to help fill in when its top-selling meds Rituxan, Herceptin and Avastin begin to battle biosimilar competitions later this decade. The two early-stage melanoma studies announced Monday were very small, but the results strong enough to embolden Roche to move forward.

"Even when the data they are presenting was taken from a sample of only a few patients, the efficacy without the use of any chemotherapy is certainly extraordinarily high," Zurich Cantonal Bank analyst Michael Nawrath wrote in an investor note (as quoted by Reuters).

In one study in 30 previously untreated patients with BRAF-positive melanoma, the PD-L1 inhibitor shone in combination with Roche’s MEK enzyme inhibitor Cotellic and BRAF blocker Zelboraf. The cocktail delivered an 83% response rate--or 24 patients--with a complete response in three of them, the Phase Ib study found.

The regimen was well-tolerated as well, Roche said; 40% of patients saw side effects that resolved with “appropriate interventions.”

In the other study, a Phase Ib test in 22 melanoma patients who hadn’t previously been treated with a PD-1/PD-L1 drug, the one-two punch of Tecentriq plus Cotellic performed in those with and without the BRAF mutation. The response rate was lower here--45% overall--but the study was long enough to generate some survival data. The combo held off cancer progression for 12 months, 15.7 months in the BRAF-positive patients and 11.9 months in the non-BRAF group.

Putting Tecentriq together with Cotellic and Zelboraf would not only broaden Tecentriq’s patient base, but could add new oomph to Cotellic and Zelboraf sales as well. Each of the two meds has its melanoma-fighting niche; Zelboraf is approved on its own to treat BRAF-positive melanoma, and Cotellic is approved alongside Zelboraf in a regimen designed to stave off treatment resistance that tends to crop up with BRAF inhibitors.

Zelboraf was first approved in 2011, so it’s no surprise that it’s the sales leader among the trio, with 160 million Swiss francs in the first nine months of this year. Tecentriq brought in 77 million francs over the same period, while Cotellic delivered 30 million.

“We are encouraged by these early results which demonstrate a high proportion of people responded to these investigational combination therapies,” Roche CMO Sandra Horning said in a statement. “The results suggest that the combination of Tecentriq with our BRAF and MEK targeted agents may extend the established benefits of the approved monotherapy and combination approaches of these medicines.”

In addition to testing combos of its own meds, the Swiss drugmaker has teamed up with a cadre of partners on other cocktails, including a September tie-up with Hanmi and a CAR-T deal inked with Kite Pharma in March. Twenty of its combo trials include Tecentriq, a PD-L1 immunotherapy first approved in bladder cancer earlier this year and lung cancer just last month.