K. Patel, J. M. Rhodes, L. Mountjoy, J. H. Christensen, M. Hutchings, P. Shaughnessy, N. Farhadfar, C. Tam, J. H. Baird, A. Ramakrishnan, M. Jak, K. Dorritie, A. Barraclough, D. Morillo, Y. Serroukh, M. Schwede, A. Abdulgawad, L. Magnano, M. O'Reilly, J. Kuruvilla, Y. Koh, U. Farooq, W. S. Kim, J. Bussolari, M. Beelen, J. S. Larsen, M. Suraneni, J. Wu, L. Slaets, A. Perales-Puchalt, A. Banerjee, M. Ku
{"title":"cd19 / cd20双特异性嵌合抗原受体（car） t细胞治疗复发/难治性（r / r）大b细胞淋巴瘤（lbcl）的全球1b期研究","authors":"K. Patel, J. M. Rhodes, L. Mountjoy, J. H. Christensen, M. Hutchings, P. Shaughnessy, N. Farhadfar, C. Tam, J. H. Baird, A. Ramakrishnan, M. Jak, K. Dorritie, A. Barraclough, D. Morillo, Y. Serroukh, M. Schwede, A. Abdulgawad, L. Magnano, M. O'Reilly, J. Kuruvilla, Y. Koh, U. Farooq, W. S. Kim, J. Bussolari, M. Beelen, J. S. Larsen, M. Suraneni, J. Wu, L. Slaets, A. Perales-Puchalt, A. Banerjee, M. Ku","doi":"10.1002/hon.70093_104","DOIUrl":null,"url":null,"abstract":"<p><b>Introduction</b>: CD19 CAR T-cell therapies have transformed the treatment (tx) of R/R LBCL, with complete response rates (CRR) of up to 58% in 3L or greater setting. However, most patients (pts) relapse, in part due to antigen escape. Dual targeting of 2 validated antigens may overcome drug resistance. In a first-in-human study in China, C-CAR039, an autologous anti-CD19/CD20 bispecific CAR T-cell therapy, showed a CRR of 86% in pts with R/R LBCL and PFS and OS were not reached at 30mo median follow up (FU). We report results from the first global phase 1b study of JNJ-90014496 (formerly C-CAR039) in adult pts with R/R LBCL (NCT05421663).</p><p><b>Methods</b>: Dose levels: 2.0 million (M) CAR+ T-cell/kg (weight-based); 150M and 75M CAR+ T-cells (fixed). Primary endpoints: safety and RP2D. Secondary endpoints: objective response rate (ORR), CRR, time to first response, pharmacokinetics (PK).</p><p><b>Results</b>: As of February 2025, 48 pts with CAR T-naive, heavily pretreated R/R LBCL were infused: 2.0M CAR+ T-cells/ kg, <i>n</i> = 18; 150M, <i>n</i> = 8; 75M, <i>n</i> = 22. 46% had ≥ 2 prior lines of therapy; 65% had bridging therapy. Median FU was 6mo.</p><p>Across all doses, 38 (79%) pts had CRS (grade [G]1, 52%; G2, 23%; G3, 4%): median time to onset and median duration of 3d (range, 1–6) and 5d (range, 1–42), respectively. 7 (15%) pts had ICANS (G1, 8%; G3, 6%): median onset and median duration of 3d (range, 3–12) and 8d (range 1–89), respectively. G3/4 and serious tx-emergent adverse events (TEAEs) were reported in 40 (83%) and 12 (25%) pts, respectively. No tx-related deaths occurred. G3/4 TEAEs ≥ 15% frequency were neutropenia (77%), leukopenia (21%), anemia (19%), and thrombocytopenia (17%); 6% of pts had G3 infections.</p><p>In 42 evaluable pts, investigator-assessed ORR and CRR by Lugano criteria were 90.5% (95% CI: 77.4–97.3) and 76.2% (95% CI: 60.5–87.9; Figure), respectively. Median time to response was 1.0mo (range, 0.8–1.9).</p><p>At RP2D of 75M CAR+ T-cells (<i>n</i> = 22), 19 (86%) pts had CRS (G1, 68%; G2, 18%; no G3/4). 1 (5%) pt had G1 ICANS (no G3/4 ICANS). At RP2D, 17 (77%) pts had G3/4 TEAEs and 5 (23%) pts had serious TEAEs. G3/4 TEAEs ≥ 15% frequency at RP2D were neutropenia (68%) and lymphopenia (18%); 1 pt had G3 infection.</p><p>At RP2D in 20 evaluable pts with 3-mo median FU, ORR was 95.0% (95% CI: 75.1–99.9) and CRR was 80.0% (95% CI: 56.3–94.3; Figure).</p><p>JNJ-90014496 C<sub>max</sub> and AUC<sub>0-29d</sub> at 75M CAR+ T-cells were comparable to 2.0M CAR+ T-cells/kg and 150M CAR+ T-cells. Median t<sub>max</sub> was seen on Day15 at 75M CAR+ T-cells versus on Day13 at other doses. High inter-pt variability was seen at each dose.</p><p><b>Conclusions:</b> The safety, efficacy, and PK profile support selection of 75M CAR+ T-cells as the RP2D of JNJ-90014496 in R/R LBCL. CRR of 80% and no G3/4 ICANS/CRS from this first global study are promising, confirm previous findings in Chinese pts, and compare favorably to historical data with approved anti-CD19 CAR T-cell therapies. Longer FU is ongoing to confirm durability and further deepening of responses.</p><p><b>Research</b> <b>funding declaration:</b> This study is supported by Johnson & Johnson.</p><p><b>Encore Abstract:</b> EHA 2025</p><p><b>Keywords:</b> cellular therapies; aggressive B-cell non-Hodgkin lymphoma; cellular therapies</p><p><b>Potential sources of conflict of interest:</b></p><p><b>K. Patel</b></p><p><b>Consultant or advisory role:</b> AstraZeneca, ADC Therapeutics, AbbVie, BeiGene, Bristol Myers Squibb, Caribou, Century Therapeutics, Fate Therapeutics, Genentech/Roche, Janssen, Kite Pharma, Lilly/Loxo, Merck, Nurix Therapeutics, Pfizer</p><p><b>Other remuneration:</b> Research funding (to institution): Accutar, Arvinas, AstraZeneca, AbbVie, Bristol Myers Squibb, Caribou, CRISPR therapeutics, Century Therapeutics, Fate Therapeutics, Genentech/Roche, Johnson & Johnson, Kite, Lilly/Loxo, Merck, Nurix Therapeutics, Pfizer, Xencor</p><p><b>J. M. Rhodes</b></p><p><b>Consultant or advisory role:</b> Abbvie, AstraZeneca, ADC Therapeutics, Beigene, BMS, Epizyme, Genentech, GenMab, Johnson & Johnson, Loxo Oncology, Morphosys, Pharmacyclics, Pfizer</p><p><b>Honoraria:</b> Aptitude, Curio Science, MJH Life Sciences, Ideology Health</p><p><b>Other remuneration:</b> Research funding: Acerta, Abbvie, Beigene, Epizyme, Johnson & Johnson, Loxo Oncology, Merck, Oncternal, Pharmacyclics, Velosbios</p><p><b>M. Hutchings</b></p><p><b>Consultant or advisory role:</b> AbbVie, AstraZeneca, Genmab, Johnson & Johnson, Merck, Roche, Takeda</p><p><b>Honoraria:</b> AbbVie, AstraZeneca, Genmab, Johnson & Johnson, Merck, Roche, Takeda</p><p><b>Other remuneration:</b> Research support (institution): AbbVie, Arvinas, AstraZeneca, Bristol Myers Squibb, Celgene, Genentech, Genmab, Incyte, Johnson & Johnson, Merck, Novartis, Pfizer, Roche, Takeda</p><p><b>P. Shaughnessy</b></p><p><b>Consultant or advisory role:</b> Autolus, Bristol Myers Squibb, Kite Pharma, Sanofi</p><p><b>Honoraria:</b> Sanofi</p><p><b>N. Farhadfar</b></p><p><b>Consultant or advisory role:</b> Incyte; Omeros, Sanofi</p><p><b>Other remuneration:</b> Medical monitor: Blood and Marrow Transplant Clinical Trial Network; DSMB member: Chronic GVHD Consortium</p><p><b>C. Tam</b></p><p><b>Honoraria:</b> AbbVie, AstraZeneca, BeiGene, Johnson & Johnson and LOXO</p><p><b>J. H. Baird</b></p><p><b>Honoraria:</b> Kite Pharma</p><p><b>Other remuneration:</b> Research funding: CARGO Therapeutics, Genentech-Roche, Johnson & Johnson, Regeneron Pharmaceuticals</p><p><b>A. Ramakrishnan</b></p><p><b>Consultant or advisory role:</b> Sonoma Bio</p><p><b>Other remuneration:</b> Research Funding: Autolus, BMS, Cellectis, Chimeric, Fate, Gracell/AstraZeneca, Johnson & Johnson, Juno, Kadmon, Kite, Macrogenics, Marker, Novartis, Pfizer, Poseida, Sanofi, Schrodinger, Sumitomo</p><p><b>K. Dorritie</b></p><p><b>Consultant or advisory role:</b> Bristol Myers Squibb, Johnson & Johnson</p><p><b>Honoraria:</b> Bristol Myers Squibb, Johnson & Johnson</p><p><b>Other remuneration:</b> Research funding to Institution: Bristol Myers Squibb, Genentech, Genmab, Johnson & Johnson, Kite Pharma, Hoffman LaRoche</p><p><b>A. Barraclough</b></p><p><b>Honoraria:</b> BeiGene, Gilead, Novartis, Roche</p><p><b>Educational</b> <b>grants:</b> AstraZeneca, Gilead</p><p><b>D. Morillo</b></p><p><b>Honoraria:</b> AbbVie, AstraZeneca, GlaxoSmithKline, Roche, Takeda</p><p><b>Educational</b> <b>grants:</b> Johnson & Johnson, Kite Pharma, Roche</p><p><b>M. Schwede</b></p><p><b>Consultant or advisory role:</b> AbbVie</p><p><b>A. Abdulgawad</b></p><p><b>Honoraria:</b> Johnson & Johnson, Kite Pharma</p><p><b>M. O'Reilly</b></p><p><b>Consultant or advisory role:</b> Autolus, Gilead, Kite Pharma</p><p><b>Honoraria:</b> Gilead, Johnson & Johnson, Kite Pharma, Novartis</p><p><b>J. Kuruvilla</b></p><p><b>Consultant or advisory role:</b> AbbVie, Bristol Myers Sqibb, Gilead/Kite Pharma, Merck, Roche, Seattle Genetics</p><p><b>Honoraria:</b> AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Genmab Gilead, GlaxoSmithKline, Incyte, Johnson & Johnson, Karyopharm, Eli Lilly, Merck, Novartis, Pfizer, Roche, Seattle Genetics</p><p><b>Other remuneration:</b> Research funding: Astra Zeneca, Merck, Novartis, Roche; Other: Karyopharm (DSMB)</p><p><b>Y. Koh</b></p><p><b>Consultant or advisory role:</b> BeiGene, Bristol Myers Squibb, Roche, Novartis</p><p><b>Honoraria:</b> GC Cell, GlaxoSmithKline, Johnson & Johnson, Kyowa-Kirin, Takeda</p><p><b>Other remuneration:</b> Research Funding: Bristol Myers Squibb</p><p><b>U. Farooq</b></p><p><b>Consultant or advisory role:</b> Kite Pharma, Morphosys</p><p><b>W. S. Kim</b></p><p><b>Other remuneration:</b> Grant/Research support: BeiGene, Boryong, Donga, Kyowa-Kirin, Roche, Sanofi</p><p><b>J. Bussolari</b></p><p><b>Employment or leadership position:</b> Employee of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>M. Beelen</b></p><p><b>Employment or leadership position:</b> Employee of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>J. S. Larsen</b></p><p><b>Employment or leadership position:</b> Employee of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>M. Suraneni</b></p><p><b>Employment or leadership position:</b> Employees of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>J. Wu</b></p><p><b>Employment or leadership position:</b> Employee of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>L. Slaets</b></p><p><b>Employment or leadership position:</b> Employee of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>A. Perales-Puchalt</b></p><p><b>Employment or leadership position:</b> Employee of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>A. Banerjee</b></p><p><b>Employment or leadership position:</b> Employees of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>M. Ku</b></p><p><b>Consultant or advisory role:</b> AbbVie, Roche</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_104","citationCount":"0","resultStr":"{\"title\":\"A GLOBAL PHASE 1B STUDY OF JNJ-90014496, A CD19/CD20 BI-SPECIFIC CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY, IN RELAPSED/REFRACTORY (R/R) LARGE B-CELL LYMPHOMA (LBCL)\",\"authors\":\"K. Patel, J. M. Rhodes, L. Mountjoy, J. H. Christensen, M. Hutchings, P. Shaughnessy, N. Farhadfar, C. Tam, J. H. Baird, A. Ramakrishnan, M. Jak, K. Dorritie, A. Barraclough, D. Morillo, Y. Serroukh, M. Schwede, A. Abdulgawad, L. Magnano, M. O'Reilly, J. Kuruvilla, Y. Koh, U. Farooq, W. S. Kim, J. Bussolari, M. Beelen, J. S. Larsen, M. Suraneni, J. Wu, L. Slaets, A. Perales-Puchalt, A. Banerjee, M. Ku\",\"doi\":\"10.1002/hon.70093_104\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><b>Introduction</b>: CD19 CAR T-cell therapies have transformed the treatment (tx) of R/R LBCL, with complete response rates (CRR) of up to 58% in 3L or greater setting. However, most patients (pts) relapse, in part due to antigen escape. Dual targeting of 2 validated antigens may overcome drug resistance. In a first-in-human study in China, C-CAR039, an autologous anti-CD19/CD20 bispecific CAR T-cell therapy, showed a CRR of 86% in pts with R/R LBCL and PFS and OS were not reached at 30mo median follow up (FU). We report results from the first global phase 1b study of JNJ-90014496 (formerly C-CAR039) in adult pts with R/R LBCL (NCT05421663).</p><p><b>Methods</b>: Dose levels: 2.0 million (M) CAR+ T-cell/kg (weight-based); 150M and 75M CAR+ T-cells (fixed). Primary endpoints: safety and RP2D. Secondary endpoints: objective response rate (ORR), CRR, time to first response, pharmacokinetics (PK).</p><p><b>Results</b>: As of February 2025, 48 pts with CAR T-naive, heavily pretreated R/R LBCL were infused: 2.0M CAR+ T-cells/ kg, <i>n</i> = 18; 150M, <i>n</i> = 8; 75M, <i>n</i> = 22. 46% had ≥ 2 prior lines of therapy; 65% had bridging therapy. Median FU was 6mo.</p><p>Across all doses, 38 (79%) pts had CRS (grade [G]1, 52%; G2, 23%; G3, 4%): median time to onset and median duration of 3d (range, 1–6) and 5d (range, 1–42), respectively. 7 (15%) pts had ICANS (G1, 8%; G3, 6%): median onset and median duration of 3d (range, 3–12) and 8d (range 1–89), respectively. G3/4 and serious tx-emergent adverse events (TEAEs) were reported in 40 (83%) and 12 (25%) pts, respectively. No tx-related deaths occurred. G3/4 TEAEs ≥ 15% frequency were neutropenia (77%), leukopenia (21%), anemia (19%), and thrombocytopenia (17%); 6% of pts had G3 infections.</p><p>In 42 evaluable pts, investigator-assessed ORR and CRR by Lugano criteria were 90.5% (95% CI: 77.4–97.3) and 76.2% (95% CI: 60.5–87.9; Figure), respectively. Median time to response was 1.0mo (range, 0.8–1.9).</p><p>At RP2D of 75M CAR+ T-cells (<i>n</i> = 22), 19 (86%) pts had CRS (G1, 68%; G2, 18%; no G3/4). 1 (5%) pt had G1 ICANS (no G3/4 ICANS). At RP2D, 17 (77%) pts had G3/4 TEAEs and 5 (23%) pts had serious TEAEs. G3/4 TEAEs ≥ 15% frequency at RP2D were neutropenia (68%) and lymphopenia (18%); 1 pt had G3 infection.</p><p>At RP2D in 20 evaluable pts with 3-mo median FU, ORR was 95.0% (95% CI: 75.1–99.9) and CRR was 80.0% (95% CI: 56.3–94.3; Figure).</p><p>JNJ-90014496 C<sub>max</sub> and AUC<sub>0-29d</sub> at 75M CAR+ T-cells were comparable to 2.0M CAR+ T-cells/kg and 150M CAR+ T-cells. Median t<sub>max</sub> was seen on Day15 at 75M CAR+ T-cells versus on Day13 at other doses. High inter-pt variability was seen at each dose.</p><p><b>Conclusions:</b> The safety, efficacy, and PK profile support selection of 75M CAR+ T-cells as the RP2D of JNJ-90014496 in R/R LBCL. CRR of 80% and no G3/4 ICANS/CRS from this first global study are promising, confirm previous findings in Chinese pts, and compare favorably to historical data with approved anti-CD19 CAR T-cell therapies. Longer FU is ongoing to confirm durability and further deepening of responses.</p><p><b>Research</b> <b>funding declaration:</b> This study is supported by Johnson & Johnson.</p><p><b>Encore Abstract:</b> EHA 2025</p><p><b>Keywords:</b> cellular therapies; aggressive B-cell non-Hodgkin lymphoma; cellular therapies</p><p><b>Potential sources of conflict of interest:</b></p><p><b>K. Patel</b></p><p><b>Consultant or advisory role:</b> AstraZeneca, ADC Therapeutics, AbbVie, BeiGene, Bristol Myers Squibb, Caribou, Century Therapeutics, Fate Therapeutics, Genentech/Roche, Janssen, Kite Pharma, Lilly/Loxo, Merck, Nurix Therapeutics, Pfizer</p><p><b>Other remuneration:</b> Research funding (to institution): Accutar, Arvinas, AstraZeneca, AbbVie, Bristol Myers Squibb, Caribou, CRISPR therapeutics, Century Therapeutics, Fate Therapeutics, Genentech/Roche, Johnson & Johnson, Kite, Lilly/Loxo, Merck, Nurix Therapeutics, Pfizer, Xencor</p><p><b>J. M. Rhodes</b></p><p><b>Consultant or advisory role:</b> Abbvie, AstraZeneca, ADC Therapeutics, Beigene, BMS, Epizyme, Genentech, GenMab, Johnson & Johnson, Loxo Oncology, Morphosys, Pharmacyclics, Pfizer</p><p><b>Honoraria:</b> Aptitude, Curio Science, MJH Life Sciences, Ideology Health</p><p><b>Other remuneration:</b> Research funding: Acerta, Abbvie, Beigene, Epizyme, Johnson & Johnson, Loxo Oncology, Merck, Oncternal, Pharmacyclics, Velosbios</p><p><b>M. Hutchings</b></p><p><b>Consultant or advisory role:</b> AbbVie, AstraZeneca, Genmab, Johnson & Johnson, Merck, Roche, Takeda</p><p><b>Honoraria:</b> AbbVie, AstraZeneca, Genmab, Johnson & Johnson, Merck, Roche, Takeda</p><p><b>Other remuneration:</b> Research support (institution): AbbVie, Arvinas, AstraZeneca, Bristol Myers Squibb, Celgene, Genentech, Genmab, Incyte, Johnson & Johnson, Merck, Novartis, Pfizer, Roche, Takeda</p><p><b>P. Shaughnessy</b></p><p><b>Consultant or advisory role:</b> Autolus, Bristol Myers Squibb, Kite Pharma, Sanofi</p><p><b>Honoraria:</b> Sanofi</p><p><b>N. Farhadfar</b></p><p><b>Consultant or advisory role:</b> Incyte; Omeros, Sanofi</p><p><b>Other remuneration:</b> Medical monitor: Blood and Marrow Transplant Clinical Trial Network; DSMB member: Chronic GVHD Consortium</p><p><b>C. Tam</b></p><p><b>Honoraria:</b> AbbVie, AstraZeneca, BeiGene, Johnson & Johnson and LOXO</p><p><b>J. H. Baird</b></p><p><b>Honoraria:</b> Kite Pharma</p><p><b>Other remuneration:</b> Research funding: CARGO Therapeutics, Genentech-Roche, Johnson & Johnson, Regeneron Pharmaceuticals</p><p><b>A. Ramakrishnan</b></p><p><b>Consultant or advisory role:</b> Sonoma Bio</p><p><b>Other remuneration:</b> Research Funding: Autolus, BMS, Cellectis, Chimeric, Fate, Gracell/AstraZeneca, Johnson & Johnson, Juno, Kadmon, Kite, Macrogenics, Marker, Novartis, Pfizer, Poseida, Sanofi, Schrodinger, Sumitomo</p><p><b>K. Dorritie</b></p><p><b>Consultant or advisory role:</b> Bristol Myers Squibb, Johnson & Johnson</p><p><b>Honoraria:</b> Bristol Myers Squibb, Johnson & Johnson</p><p><b>Other remuneration:</b> Research funding to Institution: Bristol Myers Squibb, Genentech, Genmab, Johnson & Johnson, Kite Pharma, Hoffman LaRoche</p><p><b>A. Barraclough</b></p><p><b>Honoraria:</b> BeiGene, Gilead, Novartis, Roche</p><p><b>Educational</b> <b>grants:</b> AstraZeneca, Gilead</p><p><b>D. Morillo</b></p><p><b>Honoraria:</b> AbbVie, AstraZeneca, GlaxoSmithKline, Roche, Takeda</p><p><b>Educational</b> <b>grants:</b> Johnson & Johnson, Kite Pharma, Roche</p><p><b>M. Schwede</b></p><p><b>Consultant or advisory role:</b> AbbVie</p><p><b>A. Abdulgawad</b></p><p><b>Honoraria:</b> Johnson & Johnson, Kite Pharma</p><p><b>M. O'Reilly</b></p><p><b>Consultant or advisory role:</b> Autolus, Gilead, Kite Pharma</p><p><b>Honoraria:</b> Gilead, Johnson & Johnson, Kite Pharma, Novartis</p><p><b>J. Kuruvilla</b></p><p><b>Consultant or advisory role:</b> AbbVie, Bristol Myers Sqibb, Gilead/Kite Pharma, Merck, Roche, Seattle Genetics</p><p><b>Honoraria:</b> AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Genmab Gilead, GlaxoSmithKline, Incyte, Johnson & Johnson, Karyopharm, Eli Lilly, Merck, Novartis, Pfizer, Roche, Seattle Genetics</p><p><b>Other remuneration:</b> Research funding: Astra Zeneca, Merck, Novartis, Roche; Other: Karyopharm (DSMB)</p><p><b>Y. Koh</b></p><p><b>Consultant or advisory role:</b> BeiGene, Bristol Myers Squibb, Roche, Novartis</p><p><b>Honoraria:</b> GC Cell, GlaxoSmithKline, Johnson & Johnson, Kyowa-Kirin, Takeda</p><p><b>Other remuneration:</b> Research Funding: Bristol Myers Squibb</p><p><b>U. Farooq</b></p><p><b>Consultant or advisory role:</b> Kite Pharma, Morphosys</p><p><b>W. S. Kim</b></p><p><b>Other remuneration:</b> Grant/Research support: BeiGene, Boryong, Donga, Kyowa-Kirin, Roche, Sanofi</p><p><b>J. Bussolari</b></p><p><b>Employment or leadership position:</b> Employee of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>M. Beelen</b></p><p><b>Employment or leadership position:</b> Employee of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>J. S. Larsen</b></p><p><b>Employment or leadership position:</b> Employee of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>M. Suraneni</b></p><p><b>Employment or leadership position:</b> Employees of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>J. Wu</b></p><p><b>Employment or leadership position:</b> Employee of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>L. Slaets</b></p><p><b>Employment or leadership position:</b> Employee of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>A. Perales-Puchalt</b></p><p><b>Employment or leadership position:</b> Employee of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>A. Banerjee</b></p><p><b>Employment or leadership position:</b> Employees of Johnson & Johnson and may hold stock/stock options in the company</p><p><b>M. Ku</b></p><p><b>Consultant or advisory role:</b> AbbVie, Roche</p>\",\"PeriodicalId\":12882,\"journal\":{\"name\":\"Hematological Oncology\",\"volume\":\"43 S3\",\"pages\":\"\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-06-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_104\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hematological Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/hon.70093_104\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.70093_104","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
A GLOBAL PHASE 1B STUDY OF JNJ-90014496, A CD19/CD20 BI-SPECIFIC CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY, IN RELAPSED/REFRACTORY (R/R) LARGE B-CELL LYMPHOMA (LBCL)
Introduction: CD19 CAR T-cell therapies have transformed the treatment (tx) of R/R LBCL, with complete response rates (CRR) of up to 58% in 3L or greater setting. However, most patients (pts) relapse, in part due to antigen escape. Dual targeting of 2 validated antigens may overcome drug resistance. In a first-in-human study in China, C-CAR039, an autologous anti-CD19/CD20 bispecific CAR T-cell therapy, showed a CRR of 86% in pts with R/R LBCL and PFS and OS were not reached at 30mo median follow up (FU). We report results from the first global phase 1b study of JNJ-90014496 (formerly C-CAR039) in adult pts with R/R LBCL (NCT05421663).
Methods: Dose levels: 2.0 million (M) CAR+ T-cell/kg (weight-based); 150M and 75M CAR+ T-cells (fixed). Primary endpoints: safety and RP2D. Secondary endpoints: objective response rate (ORR), CRR, time to first response, pharmacokinetics (PK).
Results: As of February 2025, 48 pts with CAR T-naive, heavily pretreated R/R LBCL were infused: 2.0M CAR+ T-cells/ kg, n = 18; 150M, n = 8; 75M, n = 22. 46% had ≥ 2 prior lines of therapy; 65% had bridging therapy. Median FU was 6mo.
Across all doses, 38 (79%) pts had CRS (grade [G]1, 52%; G2, 23%; G3, 4%): median time to onset and median duration of 3d (range, 1–6) and 5d (range, 1–42), respectively. 7 (15%) pts had ICANS (G1, 8%; G3, 6%): median onset and median duration of 3d (range, 3–12) and 8d (range 1–89), respectively. G3/4 and serious tx-emergent adverse events (TEAEs) were reported in 40 (83%) and 12 (25%) pts, respectively. No tx-related deaths occurred. G3/4 TEAEs ≥ 15% frequency were neutropenia (77%), leukopenia (21%), anemia (19%), and thrombocytopenia (17%); 6% of pts had G3 infections.
In 42 evaluable pts, investigator-assessed ORR and CRR by Lugano criteria were 90.5% (95% CI: 77.4–97.3) and 76.2% (95% CI: 60.5–87.9; Figure), respectively. Median time to response was 1.0mo (range, 0.8–1.9).
At RP2D of 75M CAR+ T-cells (n = 22), 19 (86%) pts had CRS (G1, 68%; G2, 18%; no G3/4). 1 (5%) pt had G1 ICANS (no G3/4 ICANS). At RP2D, 17 (77%) pts had G3/4 TEAEs and 5 (23%) pts had serious TEAEs. G3/4 TEAEs ≥ 15% frequency at RP2D were neutropenia (68%) and lymphopenia (18%); 1 pt had G3 infection.
At RP2D in 20 evaluable pts with 3-mo median FU, ORR was 95.0% (95% CI: 75.1–99.9) and CRR was 80.0% (95% CI: 56.3–94.3; Figure).
JNJ-90014496 Cmax and AUC0-29d at 75M CAR+ T-cells were comparable to 2.0M CAR+ T-cells/kg and 150M CAR+ T-cells. Median tmax was seen on Day15 at 75M CAR+ T-cells versus on Day13 at other doses. High inter-pt variability was seen at each dose.
Conclusions: The safety, efficacy, and PK profile support selection of 75M CAR+ T-cells as the RP2D of JNJ-90014496 in R/R LBCL. CRR of 80% and no G3/4 ICANS/CRS from this first global study are promising, confirm previous findings in Chinese pts, and compare favorably to historical data with approved anti-CD19 CAR T-cell therapies. Longer FU is ongoing to confirm durability and further deepening of responses.
Researchfunding declaration: This study is supported by Johnson & Johnson.
期刊介绍：
Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged:
-Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders
-Diagnostic investigations, including imaging and laboratory assays
-Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases
-Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies
-Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems.
Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
