Immuno-Oncology Battle: Roche Challenges Bristol Myers Squibb and Merck with Positive Phase III NSCLC Data for Tecentriq

Last month, Bristol-Myers Squibb (BMY) disclosed an error in the Phase III data for Opdivo, an approved PD-L1 inhibitor, used as a first-line treatment for non-small cell lung cancer (NSCLC). Shortly thereafter, Roche’s Genentech (RHHBY) released positive Phase III data for Tecentriq, its second-line immunotherapy agent, in patients with advanced NSCLC. Soon after, Merck also announced data for its therapeutic drug Keytruda in this indication.

On the 19th of last month, the FDA conducted a review of Tecentriq’s efficacy in treating non-small cell lung cancer (NSCLC). Tecentriq, the first anti-PD-L1 inhibitor approved by the FDA in May, is indicated for the treatment of a specific type of bladder cancer. This recent review primarily focused on evaluating its therapeutic efficacy in two patient populations: those with NSCLC who had not responded to platinum-based chemotherapy, and those with tumors harboring mutations or ALK positivity. The agency also granted Tecentriq Breakthrough Therapy designation for these indications.

Roche has selected this drug as the cornerstone of its cancer immunotherapy strategy; like other large pharmaceutical companies’ immuno-oncology programs, it is committed to seeking advantageous partnerships that will enhance the efficacy of checkpoint-targeting inhibitors against PD-1 and PD-L1. In May, Roche reached an agreement with Kite Pharma (KITE), a developer of CAR-T (chimeric antigen receptor T-cell) therapies, to evaluate the efficacy of Tecentriq in combination with Kite’s KTE-C19 for the treatment of refractory malignant non-Hodgkin lymphoma (NHL).

Norwegian Biopharma stated that during the American Society of Clinical Oncology (ASCO) conference call in June, it was mentioned that following clinical staging, Roche has at least 10 molecules for cancer immunotherapy, including Tecentriq, with another 20 under review.

Roche’s goal is the immuno-oncology trilogy: activating the front end of the immune system, breaking through immune barriers, and bypassing normal immune regulation. Although immunotherapy has made significant advances compared with previous treatments, it remains ineffective for most patients. This is the problem Roche hopes to address through collaborations with other companies. However, biopharmaceutical companies are now seeking efficacy across all fronts, many approaches for which are unlikely to be applicable in clinical practice.

“Through scientifically rational combinations, 70% to 80% of patients receiving immune checkpoint inhibitor monotherapy have achieved clinical benefit,” Roche CEO Daniel O’Day noted during the ASCO conference call in June. “Since this time last year, the number of combination therapies has more than doubled. We now have over 50 trials underway, with more than 30 of them being combination studies. And these figures are not yet the most up-to-date.”

Latest data indicate that Tecentriq met the expected overall survival benchmarks in both the overall population and the specific subgroup of patients with PD-L1 expression. The trial used docetaxel to treat patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had not responded to platinum-based chemotherapy.

Among 1,225 patients, half were randomly selected to receive either docetaxel or Tecentriq injections every three weeks. The trial aimed to analyze the objective response rate (ORR), progression-free survival (PFS), duration of response (DOR), and safety.

Roche Genentech stated that it expects to present the full results at a closed-door medical conference later this year.

Bristol-Myers Squibb’s Opdivo recently failed in Phase III clinical trials for first-line non-small cell lung cancer (NSCLC). In June, Merck released data from its Keytruda malignancy trials. Both drugs have received FDA approval for second-line use, but this still poses a challenge for Tecentriq.

“If Tecentriq achieves a broad indication profile similar to that of Opdivo, it will narrow Opdivo’s lead in the PD-1 market,” noted Leerink analyst Seamus Fernandez. “However, Roche appears to be positioning Tecentriq to capitalize on its safety advantages in the PD-L1 space, with all data from the OAK trial serving as the key differentiator for assessing safety and efficacy. Broadly speaking, the most significant distinctions between PD-1 and PD-L1 inhibitors lie in their safety and efficacy profiles.”

He concluded, “Following the failure of Bristol-Myers Squibb’s CM-026 trial, the OAK trial in second-line patients quickly achieved success, which undoubtedly poses a challenge to Bristol-Myers Squibb’s current leadership position.”