Priming immunotherapy with radiotherapy (RT) in advanced non-small cell lung cancer (NSCLC) and head and neck squamous cell cancer (HNSCC): Interim analysis of phase II clinical trial.

Authors

Aasems Jacob

Aasems Jacob

University of Kentucky, Lexington, KY

Aasems Jacob , Alexander Kreimer , Jing Wei , Jianrong Wu , Lauren Corum , Ellen Reusch , Jerold Woodward , Donald Cohen , Subbarao Bondada , Val R. Adams , Rachael Morgan , Ronald C. McGarry , William H. St Clair , Mahesh R. Kudrimoti , Zin Myint , Susanne M. Arnold , John L. Villano

Organizations

University of Kentucky, Lexington, KY

Research Funding

Other
University of Kentucky Markey Cancer Center’s Cancer Center Support Grant

Background: Preclinical models demonstrate that combined RT with immune checkpoint inhibitor (ICI) results in specific CD8+ T-cell phenotype associated with a tumor-reactive population resulting in significant tumor response. Sequential treatment could allow radiation to release tumor antigens from immune inaccessible areas and provide robust anti-tumor immune response with ICI. We report an interim analysis of the phase II clinical trial evaluating the efficacy and safety of the combination. Methods: Advanced NSCLC and HNSCC patients who had initiated on FDA approved single-agent ICI were eligible. Patients were given SBRT (BED>100Gy) or 30 Gy fractionated RT delivered as a 3-dimensional dose to a single metastatic site within 14 days of the first ICI dose. Primary objective was 6-month PFS and secondary objectives were safety and tolerability, 1Y PFS and OS. This interim analysis was done after enrollment of 43 patients. Results: Between 10/2017 to 1/2021, 43 patients were enrolled, and 38 included in this analysis. Median age was 62 years; 26 patients were male. 9 patients received ICI for NSCLC as first-line, 7 for NSCLC second-line and 22 for HNSCC second-line. 24 patients received pembrolizumab and 14 nivolumab; 21 had SBRT and 17 fractionated RT. Median follow up duration was 11.8m (range: 2.7 - 31.4m) for patients without progressive disease (PD). 10 patients were off-study, 7 continuing treatment. 15 died and 26 had PD. 14 patients died of malignancy and cause of death for one patient was unknown. 6-month PFS was 49.19% with median PFS of 5.5 months. (table) Fifty-two grade-3-5 adverse events (AEs) were reported among 21 subjects. Most common were transaminitis (n=15), lymphopenia (n=8), and GI side effects (n=4). Treatment related AEs included 19 grade-3 events, and none were grade 4/5. Two grade-5 AEs were from PD (oral bleeding and unspecified). There were 20 grade-1/2 and 3 grade-3 immune related adverse events (IRAEs). No grade-4/5 IRAEs were reported. Two patients discontinued treatment due to grade 3 transaminitis. Conclusions: Interim analysis shows that 6m PFS was acceptable with majority of patients being second-line metastatic HNSCC who historically had mPFS of 2.1-2.3 months and mOS 7.7-8.4 months in Checkmate-141/KEYNOTE-040 trials. Hence, the combination is of further interest and accrual will continue to reach the goal. The combination therapy was tolerable without unexpected AEs. Majority of deaths were from disease progression. No treatment related grade 4/5 adverse events were reported. Two patients discontinued treatment due to grade-3 IRAE. Clinical trial information: NCT03313804

Median PFS, OS and survival probabilities in the study population.


PFS
OS
Median follow-up duration
11.8m
11.5m
Median
5.5m
19.27m
Survival Probability
 6m

 12m

 24m
49.19%

32.20%

21.46%
77.68%

57.37%

40.16%

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Developmental Therapeutics—Immunotherapy

Track

Developmental Therapeutics—Immunotherapy

Sub Track

Other Checkpoint Inhibitors (Non-PD1/PDL1, Monotherapy, or Combination)

Clinical Trial Registration Number

NCT03313804

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr 2628)

DOI

10.1200/JCO.2021.39.15_suppl.2628

Abstract #

2628

Poster Bd #

Online Only

Abstract Disclosures