Clinical Summary:

• Design/Population: The phase 3 EA5142 (ALCHEMIST) trial randomized 935 patients with resected stage IB-IIIA EGFR/ALK-negative non-small cell lung cancer to receive eihter adjuvant nivolumab for up to 1 year or observation following standard adjuvant therapy.
• Key Outcomes: Adjuvant nivolumab did not improve disease-free survival in the overall population or in patients with PD-L1 expression ≥50%. Grade ≥3 treatment-related adverse events occurred in 25% of patients receiving nivolumab.
• Clinical Relevance: These findings do not support routine use of adjuvant nivolumab in resected EGFR/ALK-negative NSCLC and highlight the need for improved biomarker-driven patient selection.

Jamie Chaft, MD, Memorial Sloan Kettering Cancer Center, New York, New York, discusses results from the phase 3 EA5142 trial, part of the National Cancer Institute’s ALCHEMIST program, evaluating adjuvant nivolumab in patients with resected EGFR or ALK-negative non-small cell lung cancer (NSCLC) following standard therapy.

With a median follow-up of more than 6 years, nivolumab failed to improve disease-free survival (DFS) compared with observation in both the overall study population and the PD-L1-high subgroup. Treatment-related grade ≥3 adverse events occurred in one-quarter of patients receiving nivolumab, suggesting that adjuvant nivolumab does not provide meaningful clinical benefit in this setting despite added toxicity.

Dr Chaft presented these results at the 2026 ASCO Annual Meeting in Chicago, Illinois.

Transcript: 

Hi, I’m Jamie Chaft from Memorial Sloan Kettering Cancer Center. At ASCO 2026, I had the honor of presenting the final results of EA5142. This was a nearly 12-year-long project as part of the ALCHEMIST umbrella study.

To give a little background, at the time these studies were designed, all we really had before or after surgery was chemotherapy. ALCHEMIST was designed to incorporate predictive biomarker testing and targeted therapy into the curative lung cancer space. The plan was to screen 8,000 patients with resected non-small cell lung cancer for EGFR and ALK alterations and offer them the opportunity to enroll in adjuvant studies of erlotinib and crizotinib. 

EA5142 was proposed to fill an unmet need because about 80% of patients screened through ALCHEMIST with non-squamous non-small cell lung cancer would not have had a trial option. We later broadened eligibility to include squamous cell carcinoma. The ALCHEMIST screening trial was amended to add PD-L1 testing, and EA5142 was launched to test adjuvant nivolumab. 

At the time the concept was developed, nivolumab was being studied in the second-line treatment of advanced non-small cell lung cancer, and PD-L1 was just beginning to be investigated as a predictive biomarker. We enrolled 935 patients and randomized them 1:1 to adjuvant nivolumab for up to 1 year versus observation. Patients were eligible if they had non-squamous tumors that were EGFR- and ALK-negative, or squamous cell carcinoma, after completion of adjuvant chemotherapy and, if appropriate, radiotherapy. That makes this study somewhat unique, because the other adjuvant studies in this setting did not allow radiotherapy. Our study completed enrollment many years ago, and since then we’ve seen a lot of changes in the field.

While EA5142 did not demonstrate an improvement in disease-free survival, I think it provides important context for our evolving treatment landscape. What has changed since EA5142 enrolled is the clear and consistent benefit of preoperative chemoimmunotherapy. We’ve now seen both event-free survival and overall survival advantages with this approach. Many of these studies also include continuation of immunotherapy after surgery, and the contribution of that postoperative component has never really been individually investigated, so we don’t know whether we’re overtreating patients or whether we’re providing additional benefit. The adjuvant trial landscape is also somewhat confusing. We do have FDA approvals, including pembrolizumab irrespective of PD-L1 expression, and atezolizumab for higher-stage tumors—stage II and III—with PD-L1 expression. In the atezolizumab study, high tumor PD-L1 expression really appeared to drive the benefit. At the same time, we also have negative data. There was a negative study of adjuvant durvalumab in a PD-L1–positive population without EGFR or ALK alterations, and now EA5142, where there was no benefit with adjuvant nivolumab, so we need to do more work to pool these data and better understand whether adjuvant immunotherapy offers benefit, and if so, for which patients. 

We also really need to investigate the contribution of adjuvant therapy in patients who have already completed preoperative chemoimmunotherapy. One future direction for EA5142 is to reanalyze the data in a ctDNA- or MRD-positive patient population. However, there are still many more questions that need to be answered.

Source:

Chaft JE, Sun Z, Rudin CM, et al. Randomized phase III study of nivolumab after surgery and adjuvant chemotherapy in NSCLC (ECOG-ACRIN EA5142, ALCHEMIST). Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 8000.