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

FDA approves osimertinib for locally advanced, unresectable (stage III) NSCLC following chemoradiation therapy

• Tagrisso (osimertinib, AstraZeneca), for adult patients with locally advanced, unresectable (stage III) NSCLC whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.

• Efficacy was evaluated in LAURA (NCT03521154), a double blind, randomized, placebo-controlled trial in 216 adult patients.

• Osimertinib demonstrated a statistically significant improvement in PFS vs. placebo with a hazard ratio of 0.16 (95% CI: 0.10, 0.24; p-value <0.001). The median PFS was 39.1 months (95% CI: 31.5, not estimable [NE]) in the osimertinib arm and 5.6 months (95% CI: 3.7, 7.4) in the placebo arm.

• While OS results were immature at the current analysis, with 36% of pre-specified deaths for the final analysis reported, no trend towards a detriment was observed.

FDA Approves Sanofi's Sarclisa in Newly Diagnosed Multiple Myeloma

• Sarclisa (isatuximab) with bortezomib, lenalidomide, and dexamethasone approved for NDMM adults who are not eligible for autologous stem cell transplant.

• Efficacy was evaluated in IMROZ (NCT03319667), an open-label, randomized, active-controlled phase 3 trial. Enrollment was limited to patients 80 years of age and younger. A total of 446 patients were randomized (3:2) to receive Isa-VRd or VRd.

• IMROZ demonstrated an improvement in PFS in the Isa-VRd arm with a 40% reduction in risk of disease progression or death (hazard ratio 0.60 [95% CI: 0.44, 0.81]; p-value 0.0009); the median PFS was not reached (NR) (95% CI: NR, NR) in the Isa-VRd arm and was 54.3 months (95% CI: 45.2, NR) in the VRd arm.

• The most common adverse reactions (≥20%) were upper respiratory tract infection, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19 infection