OncLive’s April Roundup of Key FDA Decisions in Oncology


In case you missed it, below is your guide to the important regulatory approvals made by the FDA in April 2024.



In case you missed it, below is your guide to the important regulatory approvals made by the FDA in April 2024, including the data that supported the decisions and expert insights on the clinical implications of these pipeline updates.

Ide-Cel Snags Approval for Triple-Class Exposed R/R Multiple Myeloma

Krina K. Patel, MD, MSc

Krina K. Patel, MD, MSc

On April 4, 2024, the CAR T-cell therapy idecabtagene vicleucel (ide-cel; Abecma) was approved by the FDA for use in adult patients with relapsed or refractory multiple myeloma following two or more prior lines of therapy, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody.

The decision was based on findings from the phase 3 KarMMA-3 study (NCT03651128), which showed that the median progression-free survival (PFS) achieved with ide-cel (n = 254) was 13.3 months (95% CI, 11.8-16.1) vs 4.4 months (95% CI, 3.4-5.9) with standard regimens (n = 132), translating to a 51% reduction in the risk of disease progression or death (HR, 0.49; 95% CI, 0.38-0.64; P < .0001). The estimated median follow-up was 15.9 months. Moreover, the therapy elicited a higher overall response rate (ORR) vs what was observed with standard regimens, at 71% (95% CI, 66%-77%) and 42% (95% CI, 33%-50%), respectively (P < .0001).

“What we have learned from some of the studies like KarMMA-3 is that when you take patients in earlier lines of therapy, we think those patients are maybe not as refractory and probably will do better,” Krina K. Patel, MD, MSc, associate professor in the Department of Lymphoma/Myeloma of the Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, in Houston, told OncLive®. “In historical situations, [this] was [the case]. When patients had later lines of therapy, like after 4 lines, they were usually more refractory to some of our best therapies vs if [they] had lines two to four, [they] probably had a better response to new therapies. But because we now use anti-CD38 [antibodies], PIs, and IMiDs in first line, and by second line, we’ve usually used the other two, we end up with penta-exposed or triple-refractory disease by the third line; so now, even earlier lines are still relapsed/refractory. As such, to have something novel that I can then offer my patients is huge.”

Cilta-Cel Gets Green Light for R/R Multiple Myeloma After at Least 1 Line of Prior Therapy

Saad Z. Usmani, MD, MBA, FACP, FASCO

Saad Z. Usmani, MD, MBA, FACP, FASCO

The next day, the regulatory agency granted approval to ciltacabtagene autoleucel (cilta-cel; Carvykti) for the treatment of adult patients with relapsed or refractory multiple myeloma who have previously received at least one prior line of therapy, including a PI and an IMiD, and who are lenalidomide (Revlimid)-refractory. The decision was supported by data from the phase 3 CARTITUDE-4 study (NCT04181827) in which a 59% reduction in the risk of disease progression or death was observed with the CAR T-cell therapy (n = 208) vs standard regimens (n = 211).

Data published in the New England Journal of Medicine showed that at a median follow-up of 15.9 months, the median PFS was not evaluable (NE; 95% CI, 22.8-NE) with cilta-cel vs 12 months (95% CI, 9.8-14.0) with standard regimens (HR, 0.41; 95% CI, 0.30-0.56; P < .0001). The median overall survival (OS) with cilta-cel was not NE (95% CI, NE-NE) vs NE (95% CI, 22.97-NE) with standard regimens (HR, 0.57; 95% CI, 0.40-0.83).

“Cilta-cel will play an important role for patients with functional, high-risk and/or lenalidomide-refractory multiple myeloma who experience early relapse within the first 2 years of diagnosis,” Saad Z. Usmani, MD, MBA, FACP, FASCO, chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center in New York, New York, told OncLive in a recent interview.

Trastuzumab Deruxtecan Wins Accelerated Approval for HER2+ Solid Tumors

Ronan J. Kelly, MD, MBA

Ronan J. Kelly, MD, MBA

On the same day, the FDA granted an accelerated approval to the antibody-drug conjugate (ADC) fam-trastuzumab deruxtecan-nxki (Enhertu) for use in adult patients with unresectable or metastatic HER2-positive solid tumors who have previously received systemic therapy and have no satisfactory alternative therapeutic options based on findings from 192 patients enrolled in the phase 2 DESTINY-PanTumor02 (NCT04482309), DESTINY-Lung01(NCT03505710), and DESTINY-CRC02 (NCT04744831) trials.

DESTINY-PanTumor02 data indicated that the ADC led to an ORR of 51.4% (95% CI, 41.7%-61.0%) with a median duration of response (DOR) of 19.4 months (range, 1.3 to 27.9+). In DESTINY-Lung01, the ORR with the agent was 52.9% (95% CI, 27.8%-77.0%) with a median DOR of 6.9 months (range, 4.0 to 11.7+). Lastly, trastuzumab deruxtecan induced an ORR of 46.9% (95% CI, 34.3%-59.8%) in patients enrolled in DESTINY-CRC02, with a median DOR of 5.5 months (range, 1.3+ to 9.7+).

“This is one of the most exciting tumor-agnostic approvals we’ve seen to date, and it’s going to be game changing for many patients who maybe haven't had such great treatment options in the past,” Ronan J. Kelly, MD, MBA, told OncLive in an exclusive interview. Kelly is chief of oncology at Baylor Scott & White Health – North Texas, director of the Baylor Scott & White Charles A. Sammons Cancer Center at Baylor University Medical Center, and the W.W. Caruth Jr. Endowed Chair of Immunology at Baylor University Medical Center in Dallas.

“We are fully in the era of ADCs. We’ve gone from the era of targeted agents to the immune-oncology [IO] era, and now we’re in the era of ADCs,” Kelly added. “Question number one is: Can we give this [trastuzumab deruxtecan] to patients with lower HER2 expression? We saw data in [HER2-low] breast cancer. Can we see efficacy in other [HER2-low] tumors? That will be something that would need to be evaluated further. Then there are combination strategies, both with targeted agents and IO agents, in particular the PD-1 inhibitors. Those studies are also ongoing.”

Adjuvant Alectinib Joins ALK+ Early-Stage NSCLC Armamentarium

Later in the month, on April 18, 2024, the FDA approved alectinib (Alecensa) as an adjuvant treatment after tumor resection in patients with ALK-positive non–small cell lung cancer whose tumors are at least 4 cm or node positive based on findings from the phase 3 ALINA trial (NCT93456076).

Data revealed that at a median follow-up of 27.8 months for alectinib (n = 130) and 28.4 months for chemotherapy (n = 127) in the intention-to-treat population comprised of patients with stage IB to IIIA disease, the median disease-free survival (DFS) was not reached (NR) and 41.3 months (95% CI, 28.5-NE), respectively (HR, 0.24; 95% CI, 0.13-0.43, P < .0001). In a subset of patients with stage II to IIIA disease, the median DFS with alectinib (n = 116) or chemotherapy (n = 115) was NR vs 44.4 months (95% CI, 27.8-NE), respectively (HR, 0.24; 95% CI, 0.13-0.45; P < .0001).

In a recent OncLive On Air podcast episode, Jessica S. Donington, MD, MSCR, and Brendon M. Stiles, MD, touched on the potential surgical implications of the ALINA trial with adjuvant alectinib.

Nogapendekin Alfa Inbakicept Joins Treatment Arsenal for BCG-Unresponsive NMIBC

Karim Chamie, MD

Karim Chamie, MD

The following week, on April 22, 2024, the regulatory agency announced the approval of the first-in-class IL-15 agonist immunotherapy nogapendekin alfa inbakicept-pmln (formerly N-803; Anktiva) plus Bacillus Calmette–Guérin (BCG) for the treatment of adult patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors based on data from the phase 2/3 QUILT-3.032 trial (NCT0302285).

The agent was found to elicit a complete response rate of 62% (95% CI, 51%-73%) in evaluable patients (n = 77) with a duration of response (DOR) ranging from 0.0 months to 47.0+ months. Fifty-eight percent of patients continued to respond for at least 12 months and 40% continued to respond for at least 24 months.

Previously, in May 2023, the FDA had issued a complete response letter to the initial biologics license application (BLA) for the immunotherapy, citing deficiencies associated with the pre-license inspection of third-party contract manufacturing organizations as the reason that the application could not be greenlit in its prior form. In October 2023, the BLA was resubmitted.

“It’s fantastic news for [patients with] bladder cancer. I have said this a number of times, and I’ll say it again, while it’s never ideal to be diagnosed with bladder cancer, this era with the number of options that we have for [the disease] is definitely something that is promising,” Karim Chamie, MD, associate professor of urology at the University of California, Los Angeles, told OncLive. The FDA approval of [nogapendekin alfa inbakicept] plus BCG for patients with BCG-unresponsive bladder cancer really proves to show that we are offering patients with what we would often consider N-stage disease where they’re going to need to have their bladder removed an alternative option. This is the third drug that is FDA approved in the past few years and I think this is probably best-in-class at the moment. I think we are going to see many patients who are going to be reaching out to us and seeking access to it.”

Lutathera Becomes First Approved Option for Pediatric SSTR+ GEP-NETs

The radioligand therapy lutetium Lu 177 dotatate (Lutathera) was approved by the FDA on April 23, 2024, for use in pediatric patients aged 12 years and older with somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors, including foregut, midgut, and hindgut neuroendocrine tumors. The decision was based on pharmacokinetic, dosimetry, and safety findings from the phase 2 NETTER-P trial (NCT04711135) and efficacy data from the phase 3 NETTER-1 study (NCT01578239).

In NETTER-P, safety of the product was evaluated in 9 pediatric patients, including 4 patients with GEP-NETs. All patients received lutetium Lu 177 dotatate at 7.4 GBq (200 mCi) once every 8 weeks for 4 total doses, translating to a cumulative dose of 29.6 GBq (800 mCi). Moreover, a 2.5% Lysine-Arginine amino acid solution was administered concomitantly. The safety profile of the agent observed on the study was comparable to what had been observed in adults.

Efficacy data from NETTER-1 showed that those who received lutetium Lu 177 dotatate plus long-acting octreotide at 30 mg (n = 116) experienced a median progression-free survival (PFS) that was NR (95% CI, 18.4-NE) by independent review committee (IRC) assessment vs 8.5 months (95% CI, 6.0-9.1) with long-acting octreotide alone at 60 mg (n = 113; HR, 0.21; 95% CI, 0.13-0.32; P < .0001). The ORR by IRC in the lutetium Lu 177 dotatate and octreotide-alone arms were 13% (95% CI, 7%-19%) and 4% (95% CI, 0.1%-7%), respectively (P = .0148). The median DOR in the respective arms was NR (95% CI, 2.8-NE) and 1.9 months (95% CI, 1.9-NE), respectively.

“While GEP-NETs in children and adolescents are rare, the impact can be devastating. [The] approval addresses a critical need for new treatment options for these vulnerable patients,” Theodore W. Laetsch, MD, trial investigator and director of the Developmental Therapeutics Program at Children’s Hospital of Philadelphia, in Pennsylvania, stated in a press release. “The introduction of radioligand therapy significantly advanced how we treat GEP-NETs, and I’m encouraged that younger patients now have the potential to benefit from this innovation.”

Tovorafenib Scores Accelerated Approval for Pediatric R/R BRAF+ Low-Grade Glioma

Sarah E. Leary, MD, MS

Sarah E. Leary, MD, MS

On the same day, the regulatory agency granted accelerated approval to tovorafenib (Ojemda) for use in pediatric patients aged 6 months or older with relapsed or refractory low-grade glioma harboring a BRAF fusion or rearrangement or a BRAF V600 mutation, solidifying the agent’s place as the first systemic therapy indicated for this population.

The decision followed findings from the phase 2 FIREFLY-1 trial (NCT04775485), in which tovorafenib elicited an ORR of 51% (95% CI, 40%-63%) per Response Assessment in Pediatric Neuro-Oncology criteria in evaluable patients (n = 76) with a median DOR of 13.8 months (95% CI, 11.3-NE) among evaluable responders (n = 39). Eighty-five percent of patients had a DOR that lasted for at least 6 months and 23% continued to respond for at least 1 year. The median time to response was 5.3 months (range, 1.6-11.2).

Low-grade gliomas are the most common tumors that we see in kids; it’s a type of brain tumor and they are considered benign but we think that word is not really appropriate when something is in the brain because it’s an essential part of how we function,” Sarah E. Leary, MD, MS, attending physician and medical director of the Pediatric Brain Tumor Program at Seattle’s Children Hospital, told OncLive in a recent interview. “Low-grade glioma can be life threatening and there were no FDA-approved therapies [for this disease] until tovorafenib. It is actually the first drug to ever apply for FDA approval for this disease.” Leary is also a professor in the Department of Pediatrics at the University of Washington School of Medicine.

Trastuzumab Biosimilar Gets Green Light for HER2-Overexpressing Breast and Gastric/GEJ Cancer

On April 29, 2024, the FDA approved the trastuzumab (Herceptin) biosimilar trastuzumab-strf (HLX02; Hercessi) as an adjuvant treatment for patients with HER2-overexpressing breast cancer, treatment for patients with HER2-overexpressing metastatic breast cancer, and HER2-overexpressing metastatic gastric or GEJ adenocarcinoma. The approval was based on analytical, preclinical, and clinical findings, which included a series of head-to-head trials of the biosimilar that generated comparative quality analytical data, a phase 1 pharmacokinetic similarity trial, and a phase 3 study (NCT03084237), which demonstrated the similarity of the product with the reference drug with regard to quality, safety, and efficacy.

Tisotumab Vedotin Gets Full Approval for Recurrent or Metastatic Cervical Cancer

The last approval of the month came in the form of tisotumab vedotin-tftv (Tivdak), which was granted regular approval for use in patients with recurrent or metastatic cervical cancer with disease progression on or following chemotherapy. The ADC was previously granted accelerated approval for this indication in September 2021.

The decision was based on findings from the phase 3 innovaTV 301 study (NCT04697628) in which the ADC (n = 253) led to a median OS of 11.5 months (95% CI, 9.8-14.9) vs 9.5 months (95% CI, 7.9-10.7) with chemotherapy (n = 249; HR, 0.70; 95% CI, 0.54-0.89; P = .0038). The median PFS with tisotumab vedotin vs chemotherapy was 4.2 months (95% CI, 4.0-4.4) and 2.9 months (95% CI, 2.6-3.1), respectively (HR, 0.67; 95% CI, 0.54-0.82; P < .0001). The confirmed ORRs were 17.8% (95% CI, 13.3%-23.1%) and 5.2% (95% CI, 2.8%-8.8%), respectively (P < .0001).

“The good news from the innovaTV 301 trial is that the subgroup analysis was showing that the survival benefit was better regardless of receiving the checkpoint inhibitor before the first line or not, so that means we can expect better results by giving tisotumab vedotin even after the patients already received checkpoint inhibitors,” Keiichi Fujiwara, MD, PhD, of Saitama Medical University International Medical Center, told OncLive.

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