FDA Approval Summary: Lisocabtagene Maraleucel for Second-Line Treatment of Large B-Cell Lymphoma.

In June 2022, the FDA extended the indication for lisocabtagene maraleucel (liso-cel) to include adults with large B-cell lymphoma (LBCL) who have refractory disease or relapse within 12 months of first-line chemoimmunotherapy (CIT), as well as transplant-ineligible adults with refractory disease or relapse after first-line CIT. Two clinical trials evaluating a single infusion of liso-cel preceded by lymphodepleting chemotherapy supported the second-line indications. TRANSFORM is a randomized, phase 3, open-label trial comparing liso-cel with standard second-line therapy, including planned autologous hematopoietic stem cell transplantation (HSCT), in 184 transplant-eligible patients. On interim analysis, event-free survival (EFS) by independent review committee (IRC) assessment was statistically significantly improved for the liso-cel arm, with a stratified hazard ratio of 0.34 [95% confidence interval (CI), 0.22-0.51; P < 0.0001]; the estimated median EFS was 10.1 months in the liso-cel arm versus 2.3 months in the control arm. PILOT is a single-arm phase 2 trial of second-line liso-cel in patients who were transplant-ineligible due to age or comorbidities but had adequate organ function for chimeric antigen receptor (CAR) T-cell therapy. Among 61 patients who received liso-cel (median age, 74 years), the IRC-assessed complete response rate was 54% (95% CI, 41-67). Among patients achieving complete response, the estimated 1-year rate of continued response was 68% (95% CI, 45-83). Of the 268 patients combined who received liso-cel as second-line therapy for LBCL, cytokine release syndrome occurred in 45% (Grade 3, 1.3%) and CAR T-cell-associated neurologic toxicities occurred in 27% (Grade 3, 7%), warranting a continued risk evaluation and mitigation strategy.

Advancing Clinical Trial Design for Non-Muscle Invasive Bladder Cancer.

BACKGROUND: Despite recent drug development for non-muscle invasive bladder cancer (NMIBC), few therapies have been approved by the US Food and Drug Administration (FDA), and there remains an unmet clinical need. Bacillus Calmette-Guerin (BCG) supply issues underscore the importance of developing safe and effective drugs for NMIBC. OBJECTIVE: On November 18-19, 2021, the FDA held a public virtual workshop to discuss NMIBC research needs and potential trial designs for future development of effective therapies. METHODS: Representatives from various disciplines including urologists, oncologists, pathologists, statisticians, basic and translational scientists, and the patient advocacy community participated. The workshop format included invited lectures, panel discussions, and opportunity for audience discussion and comment. RESULTS: In a pre-workshop survey, 92% of urologists surveyed considered the development of alternatives to BCG as a high drug development priority for BCG-naïve high-risk patients. Key topics discussed included definitions of disease states; trial design for BCG-naïve NMIBC, BCG-unresponsive carcinoma in situ, and BCG-unresponsive papillary carcinoma; strengths and limitations of single-arm trial designs; assessing patient-reported outcomes; and considerations for assessing avoidance of cystectomy as an efficacy measure. CONCLUSIONS: The workshop discussed several important opportunities for trial design refinement in NMIBC. FDA encourages sponsors to meet with the appropriate review division to discuss trial design proposals for NMIBC early in drug development.