FDA Approves Breyanzi CAR T Cell Therapy for R/R  Mantle Cell Lymphoma

• Approval based on the MCL cohort (n=68) of TRANSCEND NHL 001, which enrolled adults with who had previously received at least two or more prior lines of therapy, including a BTK inhibitor

• Per label, ORR was 85.3%, with 67.6% achieving a complete response (CR). Responses were rapid and durable with a median time to response of one month (range: 0.7-3) and median duration of response of 13.3 months, with a median follow-up of 22.2 months

• Results from the primary analysis published in the Journal of Clinical Oncology (JCO) (n=83; DL1 + DL2) showed an ORR of 83.1% , with CR rate of 72.3%. Median duration of response was 15.7 months and PFS was 15.3 months

European Commission Approve Opdivo (nivolumab)-Chemo Combination for First-Line Unresectable or Metastatic Urothelial Carcinoma

• Approval based on CheckMate -901, the first Phase 3 trial in this patient population with an immunotherapy-chemotherapy combination to demonstrate survival benefit vs. chemotherapy

• With a median follow up of approx. 33 months, Opdivo in combination with cisplatin and gemcitabine provided a median OS of 21.7 months vs. 18.9 months with cisplatin-gemcitabine alone (HR: 0.78; 95% CI: 0.63, 0.96; p=0.0171)

• Becomes first concurrent immunotherapy-chemotherapy combination approved for this patient population in the European Union

First FDA approval of a targeted therapy for pediatric patients < 12 years of age with RET alterations.

Accelerated approval for selpercatinib (Retevmo, Eli Lilly and Company) for pediatric patients 2years of age and older with the following:

• Advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy;

• Advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate);

• Locally advanced or metastatic solid tumors with a RET gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.

FDA grants accelerated approval to tarlatamab for extensive stage small cell lung cancer

• Efficacy was evaluated in 99 patients with relapsed/refractory ES-SCLC with disease progression following platinum-based chemotherapy

• ORR 40% with median DOR 9.7 months (range 2.7, 20.7+). Of the 69 patients with available data regarding platinum sensitivity status, the ORR was 52% in 27 patients with platinum-resistant SCLC (defined as progression < 90 days after last dose of platinum therapy) and 31% in 42 patients with platinum-sensitive SCLC (defined as progression ≥ 90 days after last dose of platinum therapy).

• BLA reviewed utilized Project Orbis (FDA + Brazil's ANVISA, Health Canada, Israel’s Ministry of Health and the UK's MHRA). FDA reviewed under RTOR, with approval coming  1 month ahead of the goal date.

FDA Grant Accelerated Approval to CAR-T Breyanzi in 3L r/r Follicular Lymphoma

• AA based on ORR from Phase 2, single-arm TRANSCEND-FL (NCT04245839) in adults with relapsed or refractory FL after two or more lines of systemic therapy.

• Remarkably, ORR was 95.7% (95% CI: 89.5, 98.8). After a median follow up of 16.8 months, median DOR was not reached (95% CI: 18.04, NR).

• Most common nonlaboratory adverse reactions (≥20%) were cytokine release syndrome, headache, musculoskeletal pain, fatigue, constipation, and fever.

SEAGEN's Tivdak confirms benefit in recurrent or metastatic cervical cancer with disease progression on or after chemotherapy; AA PMR fulfilled

• Efficacy was evaluated in innovaTV 301 (NCT04697628), an open-label, active-controlled, multicenter, randomized trial that enrolled 502 patients with recurrent or metastatic cervical cancer who had received one or two prior systemic regimens, including chemotherapy with or without bevacizumab and/or an anti-PD-(L)-1 agent

• Median OS was 11.5 months (95% CI: 9.8, 14.9) vs. 9.5 months (95% CI: 7.9, 10.7) in the chemotherapy arm (HR 0.70 [95% CI: 0.54, 0.89] p-value 0.0038)

• Trial’s results fulfill the post-marketing requirement of the FDA's 2021 accelerated approval for this indication

Another First as FDA grant accelerated approval to tovorafenib for patients with r/r BRAF-altered pediatric low-grade glioma

• First FDA approval of a systemic therapy for the treatment of patients with pediatric LGG with BRAF rearrangements, including fusions

• Efficacy was evaluated in 76 patients enrolled in FIREFLY-1 (NCT04775485), a multicenter, open-label, single-arm trial

• ORR was 51% (95% CI: 40, 63) and median DoR was 13.8 months (95% CI: 11.3, not estimable)

First FDA approval of a radiopharmaceutical for pediatric patients 12+  with SSTR-positive GEP-NETs

• Lutathera (lutetium Lu 177 dotatate) 2018 adult indication expanded to pediatrics 12 years+ with somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors.

• Approval was based on PK, dosimetry, and safety data from NETTER-P (NCT04711135), an ongoing, open-label, single-arm study in adolescent patients with locally advanced/inoperable or metastatic SSTR-positive GEP-NETs or pheochromocytoma/paraganglioma (PPGL).

• Approval was also based on the extrapolation of efficacy outcomes observed in NETTER-1 (NCT01578239), which supported the original approval in adults.

• NETTER-P was conducted as part of a pediatric Written Request (WR) under the Best Pharmaceuticals for Children Act (BPCA).