117O - Stereotactic Body Radiotherapy (SBRT) With Pembrolizumab (pembro) for Unresected Stage I/II Non-Small-Cell Lung Cancer (NSCLC): The Randomized, Double-Blind, Phase 3 KEYNOTE-867 Study

Background

SBRT is standard of care for inoperable stage I/II NSCLC. KEYNOTE-867 (NCT03924869) assessed the addition of pembro to SBRT in patients (pts) who refused surgery or were diagnosed with inoperable stage I/II NSCLC.

Methods

Eligible pts (≥18 years) with previously untreated, histologically or cytologically confirmed stage I/II (T1 to limited T3, N0, M0) NSCLC that was inoperable, or pts who refused surgery, were randomized 1:1 to thoracic SBRT to primary tumors for ≤2 weeks plus pembro 200 mg Q3W or placebo (pbo) for ≤17 cycles (⁓1 year). Stratification factors were stage (I vs II), ECOG PS (0/1 vs 2), geographic region (East Asia vs not East Asia), and reason for no surgery (medically inoperable vs refused). Primary endpoint was EFS by BICR.

Results

448 pts were randomized to SBRT plus pembro (n=227) or pbo (n=221). Median follow-up for this interim analysis (data cutoff, June 11, 2024) was 20.6 (range, 1.3–56.8) months (mo). Median treatment duration (range) was 9.7 (0.1–16.0) mo for the pembro arm and 11.1 (<0.1–15.5) mo for the pbo arm. Median EFS (95% CI) was 31.2 (22.5–39.1) mo and 28.3 (19.8–33.1) mo, respectively (HR, 0.92; 95% CI, 0.69–1.24; P=0.2932). EFS was similar across most pt subgroups (Table). Grade ≥3 treatment-related AEs occurred in 46/226 pts (20.4%) in the pembro arm and 8/218 (3.7%) in the pbo arm; 5 (2.2%) and 0 treatment-related deaths occurred, respectively. Immune-mediated AEs and infusion reactions occurred in 87 pts (38.5%) in the pembro arm and 25 (11.5%) in the pbo arm, with 21 (9.3%) and 2 (0.9%), respectively, of grade ≥3. Grade ≥3 treatment-related pneumonitis occurred in 7 pts (3.1%) in the pembro arm and 0 in the pbo arm. Table: 117O

^aMedian (range) age of patients at baseline was 73 (50–93) yr in the pembro arm and 73 (49–87) yr in the placebo arm.

Conclusions

Adding pembro to SBRT did not improve EFS and was associated with greater toxicity vs SBRT alone in pts with inoperable stage I/II NSCLC. Based on the benefit/risk profile, the trial was stopped, and all study treatment was discontinued.

Clinical trial identification

NCT03924869; EudraCT 2018-004320-11.

Editorial acknowledgement

Medical writing assistance was provided by Aisling Towell, of ICON plc (Dublin, Ireland). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

A. Pircher: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Roche, Pfizer, Takeda, Sanofi Aventis, MSD. S. Sótér: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Roche, Bristol Myers Squibb, MSD. G. Galffy: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Roche, MSD, Pfizer, Takeda, Bristol Myers Squibb. D. Kowalski: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Bristol Myers Squibb, MSD, Pfizer, Takeda, Medison, Johnson&Johnson, Amgen, Merck KGaA. A. Hata: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Eli Lilly, MSD, Chugai, Pfizer, Boehringer Ingelheim, Taiho; Financial Interests, Institutional, Research Grant: MSD, Eli Lilly, Chugai, Taiho, Boehringer Ingelheim, AstraZeneca, AbbVie. A.A. Valdivia Bustamante: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Other, Travel and accommodation: AstraZeneca, MSD, Regeneron, Bristol Myers Squibb, Takeda. N. Frost: Financial Interests, Personal, Speaker, Consultant, Advisor: AbbVie, Amgen, BeiGene, Berlinchemie, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Janssen Oncology, Eli Lilly, Merck Serono, MSD, Novartis, Pfizer, Roche, Sanofi, Regeneron, Takeda, AstraZeneca; Financial Interests, Institutional, Research Funding: Roche. M. Monteiro: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Daiichi Sankyo, Novartis, MSD, Knight Therapeutics, Roche. A. Haridass: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Bristol Myers Squibb. M. Bouchard: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, TerSera, Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Support for meeting attendance: TerSera; Financial Interests, Institutional, Research Grant: Pfizer, MSD. M.V. Bluthgen: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Pfizer, Amgen, Bristol Myers Squibb, MSD, Roche, Takeda, Janssen; Financial Interests, Institutional, Research Funding: AstraZeneca, Roche, MSD, Bayer, Amgen. M. Ahn: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, MSD, Lilly, Merck KGaA, ONO, Roche, Takeda, Yuhan, Amgen; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Bristol Myers Squibb, ONO, Takeda, Lilly, Merck KGaA, MSD, Amgen, Novartis, Roche, YUHAN, Arcus, Pfizer, Daiichi Sankyo, Alpha Pharmaceutical, Voronoi, Eutilex. B.G.M. Hughes: Financial Interests, Personal, Advisory Board: MSD, Bristol Myers Squibb, Pfizer, Roche, AstraZeneca, Amgen, Sanofi, Eisai, Takeda. Y. Xu: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. A. Samkari: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks or ownership: Merck & Co., Inc. A. Song: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks or ownership: Merck & Co., Inc. S. Jabbour: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck & Co., Inc., Radialogica, IMX Medical, Lantern DSMC, AstraZeneca, Beigene, Deichert LLC; Financial Interests, Institutional, Research Funding: Merck & Co., Inc., NCI, Beigene, Guardant, Adlai Nortye. All other authors have declared no conflicts of interest.