FDA Approval Highlights: OncLive’s February Recap

In case you missed it, below is a recap of all drugs that have been approved by the FDA in February 2024.

Frontline NALIRIFOX Wins Approval for Metastatic Pancreatic Adenocarcinoma

On February 13, 2024, the FDA approved irinotecan liposome (Onivyde) with oxaliplatin, 5-fluorouracil, and leucovorin (NALIRIFOX) for use as a first-line treatment of patients with pancreatic adenocarcinoma.

The safety and efficacy of the combination was evaluated in the phase 3 NAPOLI 3 study (NCT04083235), in which NALIRIFOX (n = 383) resulted in a 16% reduction in the risk of death vs gemcitabine paired with nab-paclitaxel (Abraxane; n = 387). The median overall survival with was 11.1 months (95% CI, 10.0-12.1) vs 9.2 months (95% CI, 8.3-10.6), respectively (HR, 0.84; 95% CI, 0.71-0.99; P = .0403). NALIRIFOX also reduced the risk of disease progression or death by 30% vs gemcitabine/nab-paclitaxel, with median progression-free survival of 7.4 months (95% CI, 6.0-7.7) and 5.6 months (95% CI, 5.3-5.8), respectively (HR, 0.70; 95% CI, 0.59-0.85; P = .0001). The objective response rates achieved with NALIRIFOX and gemcitabine/nab-paclitaxel were 41.8% (95% CI, 36.8%-46.9%) and 36.2% (95% CI, 31.4%-41.2%).

In an exclusive interview with OncLive®, Zev A. Wainberg, MD, a professor of medicine at the University of California, Los Angeles (UCLA), as well as codirector of the UCLA Gastrointestinal Oncology Program, underscored: “It’s hard to show improvement in OS in a randomized phase 3 trial in pancreatic cancer. [That] hasn’t been done since the emergence of nab-paclitaxel and the FOLFIRINOX [leucovorin, fluorouracil, irinotecan, and oxaliplatin] regimens at around the same time [for patients with this disease]. Since then, many studies that have been done in pancreatic cancer failed to meet their end points. The fact that [NAPOLI 3] met its primary end point of OS is significant.”

Dae Won Kim, MD, an oncology specialist in the Gastrointestinal Oncology Program at Moffitt Cancer Center, in Tampa, Florida, added that although the NAPOLI 3 data support the use of NALIRIFOX over gemcitabine plus nab-paclitaxel, head-to-head comparisons of NALIRIFOX vs FOLFIRINOX have yet to be conducted in this patient population. As such, available data do not currently support the use of one regimen over another.

Tepotinib Garners Full Approval for Metastatic NSCLC and MET Exon 14 Skipping Alterations

On February 15, 2024, the regulatory agency granted regular approval to tepotinib (Tepmetko) for use in adult patients with metastatic non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations. The agent previously received accelerated approval in February 2021 when data from the phase 2 VISION study (NCT02864992) showed that tepotinib elicited ORRs of 43% in treatment-naive patients (n = 69; 95% CI, 32%-56%) and previously treated patients (n = 83; 95% CI, 33%-55%) by blinded independent review committee assessment and RECIST v1.1 criteria. The median duration of response (DOR) with the agent in these respective populations was 10.8 months (95% CI, 6.9-not estimable) and 11.1 months (95% CI, 9.5-18.5), respectively. Findings from an additional 161 patients with 28 months of DOR follow-up time supported the conversion to a traditional approval.

In evaluable treatment naive (n = 164) and previously treated (n = 149) patients, the ORRs were 57% (95% CI, 49%-65%) and 45% (95% CI, 37%-53%), respectively. In both groups, 40% and 36% of responders, respectively, continued to respond for at least 1 year.

In February 2022, the European Commission had approved tepotinib monotherapy for adult patients with advanced NSCLC harboring MET exon 14 skipping alterations who needed systemic therapy after immunotherapy and/or platinum-based chemotherapy.

Lifileucel Is First Cellular Therapy to Win Approval for Unresectable or Metastatic Melanoma

The FDA awarded accelerated approval to lifileucel (Amtagvi) for use in adult patients with unresectable or metastatic melanoma who previously received a PD-1 antibody, and if BRAF V600 positive, a BRAF inhibitor with or without a MEK inhibitor on February 16, 2024.

Data from the phase 2 C-144-01 trial (NCT02360579) indicated that when administered at the recommended dose, the ORR achieved with the cellular therapy was 31.5% (95% CI, 21.1%-43.4%) in evaluable patients (n = 73). At 6 months, 56.5% of responders continued to respond; at 9 and 12 months, these rates were 47.8% and 43.5%, respectively. The median DOR was not reached (NR; 95% CI, 4.1 months-NR), and the median time to initial response was 1.5 months.

“Lifileucel is interesting in that it’s the first-ever tumor-infiltrating lymphocyte therapy to be approved, so it has a totally different mechanism [than other agents],” Daniel Olson, MD, an assistant professor of medicine at the University of Chicago Medical Center, in Illinois, told OncLive in a recent interview. “It’s a cell therapy, so unlike other forms of immunotherapy, it uses [T cells from] a patient’s own immune system that are harvested from the tumor, isolated, and then expanded and activated outside the patient.”

Harriet Kluger, MD, added that lifileucel is likely the first of several TIL products to become available for patients with melanoma and those with other solid tumors, adding that as cell engineering technology becomes more sophisticated, cell therapy products will become increasingly targeted, and thus, better equipped against cancer cells than the bystander antigens present in patients’ bodies. Kluger is the Harvey and Kate Cushing Professor of Medicine (Oncology) and of Dermatology; director of Yale SPORE in Skin Cancer; vice chair of Translational Research, Internal Medicine; chief of the Division of Skin and Kidney Cancer; associate cancer center director of Education, Training, and Faculty Development; and deputy section chief of Medical Oncology at Yale Cancer Center in New Haven, Connecticut.

Osimertinib Plus Chemotherapy Gets Green Light for EGFR+ NSCLC

On the same day, the regulatory agency also approved osimertinib (Tagrisso) in combination with platinum-based chemotherapy for the treatment of patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations, at detected by an approved test. This decision was based on findings from the phase 3 FLAURA 2 trial (NCT04035486) in which the osimertinib regimen (n = 279) led to a median PFS of 25.5 months (95% CI, 24.7-not evaluable) vs 16.7 months (95% CI, 14.1-21.3) with osimertinib monotherapy (n = 278; HR, 0.62; 95% CI, 0.49-0.79; 2-sided P < .0001).

“[There are] several different types of benefits of the combination over osimertinib alone. We’re excited to see this move forward and have the combination available to treat our patients…,” Pasi A. Jänne, MD, PhD, senior physician and director of the Lowe Center for Thoracic Oncology, director of the Belfer Center for Applied Cancer Science, and director of the Chen-Huang Center for EGFR Mutant Lung Cancers, and the David M. Livingston, MD, chair at the Dana-Farber Cancer Institute in Boston, Massachusetts, told OncLive. “One of the areas of future research for all of us is to try to understand which of our patients truly need the more intensified combination therapy and which patients can be treated with osimertinib by itself.

“However, the approval clearly demonstrates that there is a benefit to adding chemotherapy to osimertinib as initial treatment,” added Jänne, who is also a professor of medicine at Harvard Medical School. “We’ll need to continue to study how patients do and try to better understand who needs chemotherapy, because it does come with some associated increase in AEs.

Biweekly Teclistamab Dosing Snags Approval for Relapsed/Refractory Multiple Myeloma

On February 20, 2024, the FDA approved a reduced dose of teclistamab-cqyv (Tecvayli) at 1.5 mg/kg every 2 weeks in patients with relapsed or refractory multiple myeloma who achieved and maintained a complete response (CR) or better for at least 6 months. The decision was based on data from the phase 1/2 MajesTEC-1 study (NCT03145181; NCT04557098), in which participants initially received teclistamab at 1.5 mg/kg weekly; those who achieved a confirmed CR or better for 6 months or more were able to receive the reduced dose of the agent.

Those who received the reduced dose experienced an ORR of 63.0%, with a CR or better rate of 39.4% at a median follow-up of 14.1 months. The median DOR with the agent was 18.4 months (95% CI, 14.9-estimable). Moreover, 26.7% of patients did not have minimal residual disease (MRD). In patients who achieved a CR or better, the MRD negativity rate was 46%.

“Tecvayli is the only BCMA-targeted immune-based therapy with weight-based dosing. [The] approval of biweekly dosing for eligible patients will further enable clinicians to meet the individual needs of patients who may want flexibility in their dosing schedules,” Rachel Kobos, MD, vice president, Oncology Research & Development, Johnson & Johnson Innovative Medicine, stated in a news release.

Oral Ibrutinib Suspension Gets Label Expansion in All Current Indications

Most recently, on February 26, 2024, the regulatory agency approved a label expansion for ibrutinib (Imbruvica) with an oral suspension formulation for use in adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström macroglobulinemia, and chronic graft-vs-host disease following failure with at least 1 line of systemic treatment.

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