Nivolumab Combo Does Not Meet PFS End Point in Unresectable NSCLC

Investigators of the open-label phase 3 CheckMate -73L trial (NCT04026412) assessed 925 patients with previously untreated, locally advanced stage III NSCLC not eligible to receive curative surgery across 3 treatment arms.

Combining nivolumab (Opdivo) with concurrent chemoradiotherapy (CCRT) followed by nivolumab plus ipilimumab (Yervoy) did not reach the primary end point of progression-free survival (PFS) among patients with unresectable stage III non–small cell lung cancer (NSCLC), according to a press release on findings from the phase 3 CheckMate -73L trial (NCT04026412).¹

The nivolumab-based combination did not elicit a PFS improvement compared with CCRT plus durvalumab (Imfinzi) in the trial. The safety profile of nivolumab plus CCRT followed by nivolumab/ipilimumab was comparable with prior reports of each individual agent.

Developers plan to fully assess the trial data and collaborate with investigators to present their findings to the scientific community.

“Unfortunately, adding immunotherapy concurrently with definitive chemoradiation did not improve PFS outcomes in this setting. There remains a critical need to improve long-term outcomes for these patients and we believe these results will help inform future drug development efforts in this setting,” Joseph Fiore, vice president, global program lead of thoracic cancers at Bristol Myers Squibb, said in the press release.¹

Investigators of the open-label phase 3 CheckMate -73L trial assessed 925 patients with previously untreated, locally advanced stage III NSCLC not eligible to receive curative surgery across 3 treatment arms. In arm A, patients received nivolumab plus CCRT followed by nivolumab/ipilimumab. In arm B, patients received nivolumab plus CCRT before additional nivolumab. Patients in arm C received CCRT plus durvalumab.

The trial’s primary end point was PFS per RECIST v1.1 criteria based on blinded independent central review (BICR) of outcomes in arm A vs arm C. Secondary end points included overall survival (OS), objective response rate, time to response, duration of response, and safety.

Patients 18 years and older with an ECOG performance status of 0 or 1 and locally advanced stage IIIA, IIIB, or IIIC NSCLC who were not suitable to undergo surgical resection with curative intent were eligible to enroll on the trial.² Having newly diagnosed disease and receiving no prior local or systemic anticancer therapy intended as primary treatment for locally advanced disease were additional requirements for enrollment.

Those with any medical, emotional, psychiatric, or logistical condition that would prevent them from adhering to trial protocol were ineligible for enrollment on the study. Patients were also unsuitable for enrollment if they had active infection requiring systemic therapy within 2 weeks of randomization, prior organ or tissue transplant that needed to be managed with immune suppressive agents, or prior treatment with thoracic radiotherapy.

The FDA previously approved neoadjuvant nivolumab plus platinum-containing chemotherapy for adult patients with resectable NSCLC in March 2022.³ The combination was indicated for use in patients with any PD-L1 status.

Supporting data for the approval came from the phase 3 CheckMate -816 trial (NCT02998528). The median event-free survival (EFS) was 31.6 months (95% CI, 30.2-not reached [NR]) with nivolumab/chemotherapy vs 20.8 months (95% CI, 14.0-26.7) in patients who received chemotherapy only (HR, 0.63; 95% CI, 0.45-0.87; P = .0052). Additionally, the pathologic complete response (pCR) rate was 24% (95% CI, 18.0%-31.0%) and 2.2% (95% CI, 0.6%-5.6%) in each respective arm. Data from a prespecified interim analysis highlighted an OS trend favoring the durvalumab arm, although these outcomes did not reach statistical significance (HR, 0.57; 95% CI, 0.38-0.87).

“The approval of nivolumab with platinum-doublet chemotherapy marks a turning point in how we treat resectable NSCLC and it enables us to use immunotherapy and chemotherapy as neoadjuvant treatment for patients before surgery,” trial investigator Mark Awad, MD, PhD, an associate professor of Medicine at Harvard Medical School and the associate chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, said in a press release at the time of the approval.³

References

1. Bristol Myers Squibb provides update on phase 3 CheckMate -73L trial. News release. Bristol Myers Squibb. May 10, 2024. Accessed May 13, 2024. https://tinyurl.com/3f2mt5pr
2. A study of nivolumab and ipilimumab in untreated participants with stage 3 non-small cell lung cancer (NSCLC) that is unable or not planned to be removed by surgery (CheckMate73L). ClinicalTrials.gov. Accessed May 13, 2024. https://tinyurl.com/5f3hb4aw
3. U.S. Food and Drug Administration approves Opdivo® (nivolumab) with chemotherapy as neoadjuvant treatment for certain adult patients with resectable non-small cell lung cancer. News release. Bristol Myers Squibb. March 4, 2022. Accessed May 13, 2024. https://tinyurl.com/5c3rxc4j