Neoadjuvant Durvalumab Alone or Combined with Novel Agents for Resectable, Early-Stage NSCLC: NeoCOAST Trial

In the neoadjuvant setting, immunotherapy could be an effective treatment option and could result in pathologic downstaging, which may improve surgical outcomes.^1,2 NeoCOAST is a global, randomized, phase 2 study that investigated the efficacy of neoadjuvant durvalumab alone or combined with the anti-CD73 monoclonal antibody oleclumab, the anti-NKG2A monoclonal antibody monalizumab, or the anti-STAT3 antisense oligonucleotide danvatirsen in patients with resectable early non–small-cell lung cancer (NSCLC).²

NeoCOAST included patients with previously untreated, cytologically/histologically documented, resectable, stage I (>2 cm) to IIIA NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1.2 Patients were randomly assigned 1:1:1:1 to receive durvalumab (1500 mg intravenously [IV]) alone every 4 weeks or durvalumab combined with oleclumab 3000 mg IV every 2 weeks, monalizumab 750 mg IV every 2 weeks, or danvatirsen 200 mg IV weekly for one 28-day cycle, followed by surgery. Danvatirsen monotherapy was also given on days 1, 3, and 5 of the week prior to combination treatment.²

The primary end point was investigator-assessed major pathologic response (MPR; defined as ≤10% residual viable tumor cells at the tumor site and nodes, at surgery).² Secondary end points included pathologic complete response (pCR; defined as no viable tumor cells), safety and tolerability, the feasibility of surgery, pharmacokinetics, and immunogenicity.² Exploratory end points included tumor and microbiome biomarkers and blood mRNA signatures.²

A total of 84 patients were randomly assigned to the treatment groups between March 2019 and September 2020, and 83 received treatment: 26 received durvalumab, 21 received durvalumab plus oleclumab, 20 received durvalumab plus monalizumab, and 16 received durvalumab plus danvatirsen.²

Investigators reported that MPR was observed in 11.1% (95% confidence interval [CI], 2.4-29.2) of patients receiving durvalumab, 19.0% (95% CI, 5.4-41.9) in those receiving durvalumab plus oleclumab, 30.0% (95% CI, 11.9-54.3) in those receiving durvalumab plus monalizumab, and 31.3% (95% CI, 11.0-58.7) in those receiving durvalumab plus danvatirsen.² In addition, pCR was observed in 3.7% (95% CI, 0.1-19.0), 9.5% (95% CI, 1.2-30.4), 10.0% (95% CI, 1.2-31.7%), and 12.5% (95% CI, 1.6-38.3) of patients, respectively.²

The rates of treatment-related adverse events were 34.6% with durvalumab (grade ≥3, 0%), 57.1% with durvalumab plus oleclumab (grade ≥3, 4.8%), 50.0% with durvalumab plus monalizumab (grade ≥3, 0%), and 43.8% with durvalumab plus danvatirsen (grade ≥3, 6.3%).² The majority (91.6%) of patients were able to undergo surgery without delay. Of the 7 patients who were unable to complete surgery, 5 experienced progressive or stage IV disease.²

Patients with baseline PD-L1 expression ≥1% had a better MPR rate compared with those with <1% across all treatment groups. In addition, CD73 expression was associated with greater residual viable tumor cells at surgery in patients in the durvalumab group; however, for patients treated with durvalumab plus oleclumab, high CD73 (≥10% tumor cells) was associated with reduced viable tumor cells.

The researchers concluded that 1 cycle of durvalumab combined with oleclumab, monalizumab, or danvatirsen improved MPR and pCR rates compared with durvalumab alone, with no new safety signals. It is interesting to note that the observed responses were associated with baseline tumor PD-L1 and CD73 expression levels. These findings warrant further investigation of these agents in patients with resectable NSCLC.

References

1. Chan K, Sim VR, Bille A, Zaki K. Neoadjuvant immunotherapy in early-stage non-small cell lung cancer. AME Med J. 2021;6:42.
2. Cascone T, García-Campelo R, Spicer J, et al. NeoCOAST: open-label, randomized, phase 2, multidrug platform study of neoadjuvant durvalumab alone or combined with novel agents in patients with resectable, early-stage non-small cell lung cancer. Presented at: 2022 American Association for Cancer Research Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract CT011.