In ultrafast FDA nod, Bristol Myers' Opdivo catapults I-O therapy to pre-surgery lung cancer with first glimpse of key data

While lots of regulatory priorities have been given to COVID-19 products during the pandemic, the FDA has doled out an ultrafast cancer approval within the same week of accepting an application, introducing the first pre-surgery therapy for early-stage non-small cell lung cancer (NSCLC).

Friday, Bristol Myers Squibb’s Opdivo won an FDA go-ahead for use alongside platinum-doublet chemotherapy for treating resectable NSCLC before surgery in the neoadjuvant setting.

The FDA delivered the verdict more than four months ahead of its scheduled decision date of July 13 and within five days of accepting BMS’ application with a priority review tag. It marks not just the first immunotherapy approval but the first approval for any treatment in neoadjuvant NSCLC, the FDA noted.

The green light came so early that BMS had yet to share data on how well Opdivo could stall disease recurrence, progression or death on a key clinical trial marker called event-free survival (EFS), other than a news flash saying the PD-1 inhibitor’s combination with chemo did significantly better than chemo alone. Now, we know just how much.

In the phase 3 CheckMate-816 trial, adding Opdivo to chemo in patients with stages 1b to 3a NSCLC significantly improved EFS with a 37% reduction in the risk of recurrence, progression or death, the drug’s new label shows. Patients in the Opdivo arm enjoyed a median EFS of 31.6 months versus 20.8 months for the control group.

CheckMate-816 enrolled patients regardless of their tumor PD-L1 status. It’s not immediately clear exactly how well Opdivo fared in patients with different levels of PD-L1 expression. Patients with higher PD-L1 levels are known to respond better to PD-1/L1 therapies.

“We saw pretty consistent outcomes across subgroups, meaning that this treatment should be considered as an option potentially for all patients who’re being considered surgical candidates,” Nicholas Botwood, M.D., BMS’ senior VP of U.S. medical affairs, said in an interview with Fierce Pharma.

BMS has previously reported that Opdivo takers were more likely to have no residual signs of cancer in their resected tissue on a marker called pathologic complete response. The rates were 24% for the Opdivo-chemo regimen and just 2.2% in the chemo alone arm.

At the time of the EFS analysis, data on whether neoadjuvant Opdivo could extend patients’ lives remained immature as only 26% of the patients had died. But a prespecified interim analysis showed a positive trend in favor of the BMS drug, with a death risk reduction of 43%—even though it didn’t cross the statistical significance bar yet.

Non-metastatic cases account for about 60% of NSCLC diagnoses, and, before Opdivo’s nod, about 30% to 55% of them could develop recurrence and die of the disease despite surgery, according to BMS.

“Giving treatment in the neoadjuvant setting makes a lot of sense because this is when the tumor is still present and a real opportunity for Opdivo with chemotherapy to shrink the tumor and improve surgical outcomes,” Botwood said.

While PD-1 inhibitors, especially Merck & Co.’s Keytruda, have established themselves as the standard of care in metastatic NSCLC, they only just started to help patients with early-stage resectable disease.

In October, Roche’s PD-L1 inhibitor Tecentriq—also used alongside platinum chemo—became the first immuno-oncology agent approved for post-surgery treatment of NSCLC in the adjuvant setting. That label is limited to stages 2 to 3a disease with tumor PD-L1 expression of at least 1%.

Merck recently announced that Keytruda as an adjuvant treatment topped placebo at keeping disease at bay while keeping patients alive in stages 1b to 3a NSCLC regardless of PD-L1 status. Some patients in that clinical trial have also taken adjuvant chemotherapy after surgery.

For Opdivo, a phase 3 clinical trial dubbed ANVIL by the National Cancer Institute is testing how well Opdivo works when given after surgery and chemotherapy in patients with stages 1b to 3a NSCLC. BMS’ own CheckMate-77T study is combining Opdivo with neoadjuvant chemo followed by adjuvant treatment with Opdivo monotherapy after surgery in removable NSCLC.

Opdivo’s fast neoadjuvant nod has the FDA’s Real-Time Oncology Review program to thank. The pilot scheme allows for early submission of top-line clinical trial data to get the regulatory review going before the sponsor completes the full drug application package.

The FDA conducted the current Opdivo application under Project Obis, which provides a framework for simultaneous application and review of oncology reviews among the U.S. agency and its international counterparts. Health Canada, the U.K.’s Medicines and Healthcare products Regulatory Agency and the Australian Therapeutic Goods Administration are also on this case.

Editor's Note: The story has been updated with additional comments from BMS' Nicholas Botwood, M.D.