Lisocabtagene maraleucel for relapsed or refractory chronic lymphocytic leukemia and small lymphocytic leukemia
7501. Lisocabtagene maraleucel (liso-cel) in R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Primary analysis of TRANSCEND CLL 004.
Tanya Siddiqi (City of Hope National Medical Center, Duarte, CA) presented efficacy and safety data from the primary efficacy analysis set (n=87) of TRANSCEND CLL 004, which examined lisocabtagene maraleucel (liso-cel), a CD19-directed CAR T cell product in relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The Primary Efficacy Analysis set (PEAS) was a subgroup of patients with R/R CLL/SLL that progressed on bruton tyrosine kinase inhibitors (BTKi) and failed venetoclax (ven)-based regimens (n=49), a patient group with progressively worse outcomes as treatment options become exhausted. 18% of patients in the full study population and 18% of patients in the PEAS achieved either a complete response (CR) or a CR with incomplete marrow recovery (CRi). The CR/CRi rate in the PEAS was significantly better and compared favorably to historical rates of 0 to 5%. Objective response rates for the full study population and the PEAS were 47% and 43%, respectively, and the rate of undetectable minimal residual disease (uMRD) from bone marrow was 59% for both groups. The rate of cytokine release syndrome of the entire patient population was 85% (9% grade 3, no grade 4 or 5), neurological events 45.3% (18% grade 3 and 1% grade 4). Liso-cel exhibited rapid expansion in vivo and could be detected by qPCR in patient blood up to 36 months after infusion. More expansion was observed in responders compared to non-responders and in patients with uMRD compared to those without, including patients with uMRD stable disease (n=18). These results indicate liso-cel exhibits rapid, deep, durable responses in patients with R/R CLL/SLL, including patients with disease after BTKi progression or venetoclax failure. This clinical efficacy, coupled with its manageable safety profile indicate liso-cel as a potential new treatment option for patients with R/R CLL/SLL.
Anti-PD-1 antibody toripalimab combined with chemotherapy for first-line advanced non-small cell lung cancer
9003. Final overall survival and biomarker analyses of CHOICE-01: A double-blind randomized phase 3 study of toripalimab versus placebo in combination chemotherapy for advanced NSCLC without EGFR/ALK mutations.
Lin Wu (Hunan Cancer Hospital, Xiangya School of Medicine, Central South University, Changsha, China) reported final overall survival (OS) and biomarker analyses of CHOICE-01, phase III study comparing anti-PD-1 monoclonal antibody toripalimab in combination with chemotherapy (toripalimab + chemo) to chemotherapy alone for first line treatment of advanced NSCLC without EGFR/ALK mutations. 465 treatment naïve patients participated in the study, and 309 patients received toripalimab in combination with chemotherapy (toripalimab arm) and 156 patients received a placebo with chemotherapy (placebo arm). The toripalimab arm was associated with significant improvement in OS compared to the placebo arm, with median OS of 23.8 months and 17.0 months, respectively, and a hazard ratio (HR) of 0.73. Extensive crossover occurred in the placebo arm, with 61.4% of patients receiving toripalimab upon disease progression and 65.4% of patients receiving subsequent anti-PD-(L)1 treatment. OS favored the toripalimab arm in all subgroups of PD-L1 expression levels. Toripalimab was associated with a statistically significant 11.9-month benefit in OS among patients with non-squamous NSCLC. Median OS was 27.8 months for the toripalimab arm compared to 15.9 months for the placebo arm, HR 0.49. Whole exome sequencing of patients indicated that patients with mutations in focal adhesion or IL-7 signaling pathways achieved significantly better OS and progression free survival (PFS) in the toripalimab arm. Analyses of tumor tissues and blood circulating tumor DNA (ctDNA) also indicated that high tumor mutational burden (≥ 10 mutations/Mbp) was also associated with significant improvement in PFS in the toripalimab arm. These data support the use of toripalimab with chemotherapy for advanced NSCLC, and early biomarker analyses indicate treatment may be associated with survival benefits among patients with non-squamous disease or high TMB.
For related research on predictive biomarkers in NSCLC, read this article from Harel et al in JITC.
TROP2-targeting antibody drug conjugate datopotamab deruxtecan combined with pembrolizumab with or without chemotherapy for non-small cell lung cancer in first line and later settings.
9004. TROPION-Lung02: Datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) in advanced non-small cell lung cancer (aNSCLC).
Yasushi Goto (National Cancer Center Hospital, Tokyo, Japan) reported clinical efficacy data from the phase Ib TROPION-Lung02 trial, the first study to evaluate Datopotamab deruxtecan (Dato-DXd), an antibody-drug conjugate targeting TROP2 combined with pembrolizumab with or without platinum-containing chemotherapy for advanced non-small cell lung cancer (NSCLC) without actionable genomic alterations. Patients in the Doublet Arm (n=72) received Dato-DXd with pembrolizumab, and patients in the Triplet Arm (n=64) Dato-DXd with pembrolizumab and platinum-containing chemotherapy. 58% of patients in the Doublet Arm and 75% of patients in the Triplet Arm were being treated in the first line setting, and of patient receiving therapy in the second line or greater, 19% of patients in the Doublet Arm and 25% of patients in the Triplet Arm had received prior immunotherapy. At the time of data cutoff, 36% of patients in the Doublet Arm and 46% of patients in the Triplet Arm were still receiving treatment in the study. Objective response rate (ORR; confirmed and pending) was 38% in the Doublet Arm and 49% in the Triplet Arm. Among patients receiving doublet and triplet therapy in the first-line setting, ORR was 50% and 57%, respectively. Disease control rates (DCR) were similar between the Doublet and Triplet arms among all patients (84% and 87%, respectively) and 91% for each arm in the first-line subgroup. Median duration of response (DOR) was not reached for either arm, and preliminary progression free survival in all patients was 8.3 months in the Doublet Arm and 7.8 months in the triplet arm. Deep and durable responses were observed in both arms and in the first-line subgroup, and responses were independent of PD-L1 expression levels. No new safety signals were observed since the phase I dose-finding phase. Treatment-emergent adverse events (TEAEs) of grade 3 or higher occurred in 61% of patients, and TEAEs lead to discontinuation of Dato-DXd treatment in 23% of patients in the Doublet Arm and 28% of patients in the Triplet Arm. Dato-DXd combined with pembrolizumab with or without chemotherapy exhibits encouraging anti-tumor activity against NSCLC in the first-line setting and in later settings. Phase III trials (TROPION-Lung07 and TROPION-Lung08) comparing doublet and triplet therapy with standard of care for first-line treatment of NSCLC are in progress.
Real-world outcomes of brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma among patients with prior therapies
7507. Real-world outcomes of brexucabtagene autoleucel (brexu-cel) for relapsed or refractory (R/R) mantle cell lymphoma (MCL): A CIBMTR subgroup analysis by prior treatment.
Swetha Kambhampati, MD (City of Hope National Medical Center, Duarte, CA) presented real-world, prospective non-interventional study evaluating outcomes with brexucabtagene autoleucel (brexu-cel) CAR T therapy for relapsed or refractory (R/R) mantle cell lymphoma. 380 patients who received brexu-cel for R/R MCL were included in the study, and median follow-up was 12.0 months. 86.5% of patients had prior exposure to bruton tyrosine kinase inhibitors (BTKi; this population was not represented in the ZUMA-2 study), 55.5% had received prior bendamustine, 30% had prior autologous stem cell transplant (ASCT). 22.9% had received 1-2 prior lines of therapy, and 77.1% had received 3 or more lines of therapy. Response rates were similar for this patient population and the ZUMA-2 trial, with an overall response rate (ORR) of 90% and 91%, respectively, and a complete response (CR) rate of 78% and 68%, respectively. ORR and CR rates were similar, regardless of prior exposure to treatment. CR rates were higher among patients who received brexu-cel in an earlier line of therapy (first or second) compared to 3 or more prior lines of therapy, at 88% vs 76%, respectively. Outcomes of brexu-cel with multivariate analysis were consistent, regardless of prior BTKi, bendamustine, or ASCT therapy. Prior exposure to therapy or stem cell transplant also did not significantly affect safety profiles. Although a longer follow-up is needed to contextualize response rates and long-term clinical benefits, real-world outcomes associated with brexu-cel for R/R MCL are consistent and similar to the results of the pivotal ZUMA-2 trial, regardless of prior exposure to BTKi, bendamustine, or stem cell transplant. These data also suggest that use of brexu-cel in earlier lines of therapy may be associated with higher probability of CR.