{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T12:12:33Z","timestamp":1783944753382,"version":"3.55.0"},"reference-count":46,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"unspecified","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"The Guangzhou Science and Technology Bureau Basic and Applied Basic Research Project","award":["SL2022A04J01033 (YM)"],"award-info":[{"award-number":["SL2022A04J01033 (YM)"]}]},{"name":"The Cancer Innovative Research Program of Sun Yat-sen University Cancer Center","award":["No. CIRP-SYSUCC-0028 (HZ)"],"award-info":[{"award-number":["No. CIRP-SYSUCC-0028 (HZ)"]}]},{"name":"Ascentage Pharma Group Corp Ltd.","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"The Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2024ZD0519700; 2024ZD0519705 (LZ)"],"award-info":[{"award-number":["2024ZD0519700; 2024ZD0519705 (LZ)"]}]},{"name":"The Young Talents Program of Sun Yat-sen University Cancer Center","award":["YTP-SYSUCC-0094 (YM)"],"award-info":[{"award-number":["YTP-SYSUCC-0094 (YM)"]}]},{"name":"The Chinese National Natural Science Foundation project","award":["82073396 (HZ); 82241232 (LZ)"],"award-info":[{"award-number":["82073396 (HZ); 82241232 (LZ)"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,6,3]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Overcoming tyrosine kinase inhibitor (TKI) resistance improves survival in advanced epidermal growth factor receptor (\n                      <jats:italic>EGFR<\/jats:italic>\n                      )-mutated non-small-cell lung cancer (NSCLC). We therefore examined the safety and preliminary efficacy of pelcitoclax, a B-cell lymphoma-2 (BCL-2)\/BCL-extra-large (BCL-xL) inhibitor, and osimertinib in patients with\n                      <jats:italic>EGFR<\/jats:italic>\n                      -mutated advanced NSCLC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Enrolled patients included Cohort 1 (previously progressed after third-generation TKI treatment+chemotherapy), Cohort 2 (previously progressed after first-generation or second-generation TKI treatment+chemotherapy), and Cohort 3 (TKI treatment-naive\u00b1prior chemotherapy). Patients received intravenous pelcitoclax (160 mg in dose-expansion and either 160 or 240 mg in dose-escalation) weekly and oral osimertinib 80 mg daily. Primary endpoints were safety and recommended phase 2 dose (dose-escalation), objective response rate (ORR) and safety (dose-expansion).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>64 patients were enrolled (13, dose-escalation; 51, dose-expansion): 29 patients in Cohort 1, 8 in Cohort 2, and 27 in Cohort 3. One dose-limiting toxicity occurred at pelcitoclax 240 mg, and the recommended phase 2 dose was 160 mg plus osimertinib 80 mg. The ORR was 10.7% and median progression-free survival (mPFS) 2.7 months in patients previously progressed after third-generation TKI treatment+chemotherapy (Cohort 1) and 80.8% and 16.4 months in TKI treatment-na\u00efve patients\u00b1prior chemotherapy (Cohort 3). mPFS was longer in Cohort 1 patients with high expression of BCL-xL (4.2 vs 2.7 months, p=0.058).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Pelcitoclax combined with osimertinib showed promising safety and antitumor activity in\n                      <jats:italic>EGFR<\/jats:italic>\n                      -mutated NSCLC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04001777\">NCT04001777<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014573","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T11:45:25Z","timestamp":1783943125000},"page":"e014573","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["BCL-2\/BCL-xL inhibitor pelcitoclax with osimertinib for\n                    <i>EGFR<\/i>\n                    -mutated advanced non-small-cell lung cancer: a phase 1b 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