FDA Approved 3 New Indications in Oncology in June-July 2022

The US FDA approved three new indications for cancer management between 1 June and 31 July, 2022.

  • Dabrafenib Plus Trametinib for BRAF V600E-Mutated Tumors. Accelerated approval was given to dabrafenib in combination with trametinib (Tafinlar® and Mekinist®, Novartis) for the treatment of adult and pediatric patients ≥ 6 years of age with unresectable or metastatic solid tumors with BRAF V600E mutations (except for colorectal cancer) who have progressed following prior treatment and have no satisfactory alternative treatment options. This approval was based on safety and efficacy data from 131 adult patients with BRAF V600 mutation-positive tumors included in the open-label, multiple-cohort trials BRF117019 and NCI-MATCH Subprotocol H, and 36 pediatric patients from parts C and D of CTMT212X2101 trial. The approval was supported by results from COMBI-d, COMBI-v, and BRF113928 (studies in melanoma and lung cancer described previously in product label). Altogether, the studies enrolled patients with 24 tumor types, including different subtypes of both high-grade and low-grade glioma. The major efficacy outcome measure of these studies was the overall response rate (ORR) using standard response criteria. Of the 131 adult patients, 54 (41%) experienced an objective response. Among the highest representative tumor types, the ORR was 46% for biliary tract cancer, 33% for high-grade glioma, and 50% for low-grade glioma. For the 36 pediatric patients, the ORR was 25%; the duration of response was ≥6 months for 78% of patients and ≥24 months for 44% of patients.
  • Liso-Cel for Second-Line Large B-Cell Lymphoma. Approval was granted to an autologous, CD-19-directed, chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel; Breyanzi®, Juno Therapeutics, Inc.) for adult patients with large B-cell lymphoma (LBCL) refractory to first-line chemoimmunotherapy or relapsed within 12 months of first-line chemoimmunotherapy; or patients with refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy but not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age. Approval was based on a randomized, open-label, multicenter, TRANSFORM, trial in patients with primary refractory LBCL or relapse within 12 months of achieving complete response (CR) to first-line therapy. A total of 184 patients received either a single infusion of liso-cel after lymphodepleting chemotherapy or second-line standard therapy, consisting of three cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT in patients who achieved CR or partial response (PR). Event-free survival (EFS) assessed by independent review committee (IRC) was the primary outcome. With a median follow-up of 6.2 months, the median EFS in the liso-cel group was 10.1 months vs. 2.3 months in the standard care group (hazard ratio [HR], 0.35; P < 0.0001). Approval was supported by efficacy results from the single-arm, multicenter PILOT trial, which included transplant-ineligible patients who were able to tolerate second-line CAR T-cell therapy. Among 74 patients who underwent leukapheresis, the median age was 74 years and 61 (82%) completed liso-cel treatment. The ORR was 80% and CR rate was 54%, and the responses were durable. The prescribing information includes a boxed warning for cytokine-release syndrome (CRS) and neurologic toxicities, and the treatment can be given only in specially certified hospitals. Liso-cel is not indicated for patients with primary central nervous system lymphoma.
  • Crizotinib for ALK-Positive Inflammatory Myofibroblastic Tumors. The indication for the ALK-inhibitor crizotinib (Xalkori®, Pfizer Inc.) was expanded to include adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory ALK-positive inflammatory myofibroblastic tumors (IMT). This approval was based on ORR from two multicenter, single-arm, open-label trials that included 14 pediatric patients from the ADVL0912 trial and 7 adult patients from the A8081013 trial with unresectable, recurrent, or refractory ALK-positive IMT. Among the 14 pediatric patients, 12 patients (86%) achieved objective response (assessed by IRC), and among 7 adult patients, 5 (71%) had objective responses.