FDA approves revumenib for relapsed or refractory acute leukemia with a KMT2A translocation

• Efficacy was evaluated in a single-arm cohort of an open-label, multicenter trial (NCT04065399) in 104 adult and pediatric patients (at least 30 days old) with R/R acute leukemia with a KMT2A translocation.

• CR+CRh rate was 21.2% (95% CI: 13.8, 30.3), and the median CR+CRh duration was 6.4 months (95% CI: 2.7, not estimable).

• Among the 83 patients dependent on RBC and/or platelet transfusions at baseline, 12 (14%) became independent of RBC and platelet transfusions during any 56-day post-baseline period. Of the 21 patients independent of both RBC and platelet transfusions at baseline, 10 (48%) remained transfusion independent during any 56-day post-baseline period.

• Due to an anticipated delay in commercial availability of the lowest dose strength of revumenib, which may be used to treat patients who weigh < 40 kg, revumenib will be available through an expanded access program to allow for dosing of patients who weigh < 40 kg (information available here: NCT05918913).

• This review used RTOR pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid. FDA approved this application 6 weeks early.

FDA approves obecabtagene autoleucel for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia

• Efficacy was evaluated in FELIX (NCT04404660), an open-label, multicenter, single-arm trial that enrolled adults with relapsed or refractory CD19-positive B-cell ALL.

• Of the 65 patients evaluable for efficacy, 27 patients (42%; 95% CI: 29%, 54%) achieved CR within 3 months. Median duration of CR achieved within 3 months was 14.1 months (95% CI: 6.1, not reached).  Label has a boxed warning for CRS, ICANS and T cell malignancies.

• Product granted regenerative medicine advanced therapy designation and orphan drug designation. This is the first FDA approval for Autolus Therapeutics.

FDA grant accelerated approval to asciminib (Scemblix, Novartis AG) for adult patients with newly diagnosed Ph+ CML)in chronic phase

• The efficacy of asciminib for newly diagnosed Ph+ CML in CP was evaluated in ASC4FIRST (NCT04971226), a multicenter, randomized, active-controlled, open-label trial. A total of 405 patients were randomized (1:1) to receive either asciminib or investigator-selected tyrosine kinase inhibitors (IS-TKIs) (imatinib, nilotinib, dasatinib, or bosutinib).

• The MMR rate at 48 weeks was 68% (95% CI: 61, 74) in the asciminib arm and 49% (95% CI: 42, 56) in the IS-TKIs arm (difference 19% [95% CI: 10, 28], p-value <0.001).

• Within the imatinib stratum, the MMR rate was 69% (95% CI: 59, 78) in the asciminib arm and 40% (95% CI: 31, 50) in the IS-TKIs arm (difference 30% [95% CI: 17, 42], p-value <0.001).

• Project Orbis included Health Canada and Switzerland’s Swissmedic (SMC). The application reviews are ongoing at the other regulatory agencies.

FDA approves Astellas’ Vyloy for first-line gastric or gastroesophageal junction adenocarcinoma

• In GLOW, 507 patients were randomized to receive either zolbetuximab with CAPOX chemotherapy or placebo with CAPOX chemotherapy: Median PFS was 8.2 months vs. 6.8 months in the placebo, hazard ratio 0.75; Median OS was 18.2 months vs. and 15.5 months respectively, HR 0.75 in favor.

• In SPOTLIGHT, 565 patients were randomized to receive zolbetuximab with mFOLFOX6 chemotherapy or placebo with mFOLFOX6 chemotherapy. Median PFS was 10.6 months vs. 8.7 months in the placebo/chemotherapy arm. Median OS was 18.2 months and 15.5 months respectively, HR 0.75

• The most common serious adverse reactions in SPOTLIGHT (≥2%) were vomiting, nausea, neutropenia, febrile neutropenia, diarrhea, intestinal obstruction, pyrexia, pneumonia, respiratory failure, pulmonary embolism, decreased appetite, and sepsis.

FDA Approves Novocure’s Optune Lua® for the Treatment of Metastatic Non-Small Cell Lung Cancer

• The first treatment of its kind for metastatic NSCLC, Optune Lua is approved for use concurrently with PD-1/PD-L1 inhibitors or docetaxel in adult patients with metastatic NSCLC who progressed on or after a platinum-based regimen

• Results of the pivotal Phase 3 LUNAR trial represent the first substantial improvement in median overall survival in more than 8 years for this patient population

• Optune Lua is a wearable treatment that delivers Tumor Treating Fields (TTFields), which exert physical forces on the electrically charged components of dividing cancer cells, resulting in cell death

• Device-related AEs occurred in 63.1% of patients (n=89), these were skin-related disorders under the transducer arrays. The majority of these events were low grade (Grade 1 - 2), with only 4% (n=6) experiencing Grade 3 skin toxicity that required a break from treatment.

FDA approves Genentech’s inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast cancer

• Efficacy was evaluated in INAVO120 (NCT04191499), a randomized, double-blind, placebo-controlled, multicenter trial in 325 patients

• Median PFS was 15.0 months in the inavolisib + palbociclib + fulvestrant arm and 7.3 months in the placebo + palbociclib + fulvestrant arm (HR 0.43 , p-value <0.0001)

• This Breakthrough designated review was conducted under Project Orbis, where FDA collaborated with the Australian TGA, Health Canada, and Switzerland’s Swissmedic

FDA approves neoadjuvant/adjuvant Opdivo (nivolumab) for resectable NSCLC

• Opdivo, Bristol Myers Squibb Company, approved with platinum-doublet chemotherapy as neoadjuvant treatment, followed by single-agent nivolumab after surgery as adjuvant treatment, for adults with resectable (tumors ≥ 4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements

• Efficacy was evaluated in CHECKMATE-77T (NCT04025879), a randomized, double-blind, placebo-controlled multicenter trial in 461 patients with previously untreated and resectable NSCLC

• Median EFS was not reached (95% CI: 28.9, not estimable [NE]) in the nivolumab arm and 18.4 months (95% CI: 13.6, 28.1) in the chemotherapy arm (hazard ratio 0.58 [95% CI: 0.43, 0.78]; p-value 0.00025); adverse reactions were similar to those occurring in other clinical trials of nivolumab with chemotherapy

• For this review, FDA collaborated with the Australian TGA, the Brazil's ANVISA, Health Canada, and Israel’s IMoH

FDA grants traditional approval to Lilly’s Retevmo (selpercatinib), for adult and pediatric patients 2 years of age and older with advanced or MTC with a RET mutation

• Selpercatinib previously had accelerated approval for this indication for patients 12 years of age and older in 2020. On May 29, 2024, the FDA granted accelerated approval for this indication to pediatric patients 2 years of age and older

• Efficacy was evaluated in LIBRETTO-531 (NCT04211337), a randomized, multicenter, open-label study in adults and adolescents with advanced or metastatic RET-mutant MTC

• Median PFS was not reached in the selpercatinib arm and 16.8 months (95% CI: 12.2, 25.1) in the cabozantinib/vandetanib arm (Hazard Ratio 0.280 [95% CI: 0.165, 0.475] p-value <0.0001)

• This application was granted priority review, breakthrough designation, and orphan drug designation