OncLive’s October Roundup of Key FDA Approvals in Oncology

FDA

Below is your guide to all treatment options that have been cleared by the FDA in October 2024. The recap comprises topline findings that support the regulatory decisions and features expert insights on what the implications are for clinical practice.

10/3: Perioperative Nivolumab in Resectable NSCLC

The regulatory agency approved nivolumab (Opdivo) paired with platinum-doublet chemotherapy as neoadjuvant treatment, followed by nivolumab monotherapy after surgery as adjuvant treatment, for use in adults with resectable non–small cell lung cancer (NSCLC) and no EGFR mutations or ALK rearrangements. Data from the phase 3 CheckMate-77T trial (NCT04025879) showed that those in the nivolumab arm (n = 229) experienced a medium event-free survival that was not reached (NR; 95% CI, 28.9-NR) vs 18.4 months (95% CI, 13.6-28.1) in the placebo arm (n = 232; HR, 0.58; 95% CI, 0.43-0.78; P = .00025).

Mark Awad, MD, PhD

In an exclusive interview with OncLive®, Mark Awad, MD, PhD, chief of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center, in New York, New York said, “What CheckMate-77T and others are beginning to show is that an approach like this, using chemotherapy and immunotherapy before surgery and immunotherapy after surgery, significantly reduces the risk of recurrence. As patients are followed more longitudinally in these trials, we’re seeing a clear separation in terms of how often the cancer tends to come back or not, depending on [what arm they] were randomized [to]. So, I think this is a really exciting development in lung cancer, and specifically in early-stage [disease].”

In another interview, Jonathan D. Spicer, MD, PhD, FRCS, thoracic surgical oncologist in the Division of Adult Thoracic Surgery; associate professor in the Department of Surgery, Faculty of Medicine and Health Sciences, at McGill University in Montreal, Canada; and director of the McGill University Health Center (MUHC) Thoracic Oncology Network; discussed the surgical implications for those with resectable NSCLC following the approval:

10/10: Inavolisib Triplet in PIK3CA-Mutated HR+/HER2– Advanced Breast Cancer

A week later, the regulatory agency approved inavolisib (Itovebi) paired with palbociclib (Ibrance) and fulvestrant (Faslodex) as a treatment for adult patients with endocrine-resistant, PIK3CA-mutated, hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer after recurrence on or following completion of adjuvant endocrine therapy.

Findings from the phase 3 INAVO120 trial (NCT04191499) showed that the triplet led to a 57% reduction in the risk of disease progression or death vs palbociclib/fulvestrant alone (HR, 0.43; 95% CI, 0.32-0.59; P < .0001). The median progression-free survival (PFS) in the respective arms were 15.0 months (95% CI, 11.3-20.5) and 7.3 months (95% CI, 5.6-9.3).

The approval signifies an important milestone in the therapeutic landscape of endocrine-resistant disease, according to Hope S. Rugo, MD, professor of medicine in the Department of Medicine (Hematology/Oncology), Winterhof Family Distinguished Professor of Breast Oncology, director of Breast Oncology and Clinical Trials Education, and medical director of Cancer Infusion Services at the UCSF Helen Diller Family Comprehensive Cancer Center, in San Francisco, California. In an exclusive interview, Rugo further elucidated the significance of the approval in this population:

10/15: Optune Lua in Metastatic NSCLC After Platinum-Based Chemotherapy

The FDA approved Optune Lua for concurrent use with PD-(L)1 inhibitors or docetaxel in adult patients with metastatic NSCLC with disease progression on or following a platinum-based regimen based on data from the phase 3 LUNAR trial (NCT02973789). The median overall survival (OS) achieved by those who received Optune Lua with a PD-(L)1 inhibitor or docetaxel was 13.2 months (95% CI, 10.3-15.5) compared with 9.9 months (95% CI, 8.2-12.2) with a PD-(L)1 inhibitor or docetaxel alone (P = .04).

Rupesh Rajesh Kotecha, MD

“Tumor-treating fields [TTF] has been one of the burgeoning forms of cancer treatment. It has a place in glioblastoma, as we have definitive phase 3 trials that have demonstrated improvement in OS. There have been some encouraging results from other diseases such as malignant pleural mesothelioma, and now we have data from a phase 3 trial specifically in second-line NSCLC space and it showed an improvement in OS,” Rupesh Rajesh Kotecha, MD, radiation oncologist, chief of Radiosurgery, and director of Central Nervous System Metastasis at Miami Cancer Institute in Florida, said in a recent interview. “When we’re thinking about the options for our patients, there are some treatments that need to be substituted or added to other current regimens, and this is a type of approach that really adds onto the systemic therapy that patients receive. The use of TTF can potentially improve a patient’s overall outcome, specifically their survival, without significantly adding an increased risk of adverse effects that affect quality of life.”

10/18: Zolbetuximab Plus Chemotherapy in CLDN18.2+ Gastric or GEJ Adenocarcinoma

The regulatory agency approved zolbetuximab-clzb (Vyloy)plus fluoropyrimidine- and platinum-containing chemotherapy for frontline use in adult patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma with claudin 18.2 (CLDN18.2) positivity.

Data from SPOTLIGHT showed that zolbetuximab paired with mFOLFOX6 led to a median PFS of 10.6 months (95% CI, 8.9-12.5) vs 8.7 months (95% CI, 8.2-10.3) with chemotherapy alone (HR, 0.751; 95% CI, 0.598-0.942; 1-sided P = .0066). The median OS in the respective arms was 18.2 months (95% CI, 16.4-22.9) and 15.5 months (95% CI, 13.5-16.5; HR, 0.750; 95% CI, 0.601-0.936; 1-sided P = .0053). GLOW findings showed that when zolbetuximab was paired with CAPOX, it led to a median PFS of 8.2 months (95% CI, 7.5-8.8) vs 6.8 months (95% CI, 6.1-8.1) with CAPOX alone (HR, 0.687; 95% CI, 0.544-0.866; 1-sided P = .0007). The median OS in the respective arms was 14.4 months (95% CI, 12.3-16.5) and 12.2 months (95% CI, 10.3-13.7; HR, 0.771; 95% CI, 0.615-0.965; 1-sided P = .0118).

Samuel J. Klempner, MD

Zolbetuximab works by targeting CLDN18.2, leading to tumor cell destruction through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, according to Samuel J. Klempner, MD, who is a gastrointestinal oncologist at Massachusetts General Hospital. He explained that this mechanism, combined with chemotherapy, has shown synergistic effects, making it an effective first-line treatment option for those with CLDN18.2-positive disease.

In another interview, Cindy Medina Pabon, MD, assistant professor at Sylvester Cancer Center of the University of Miami and assistant lead of GI Cancer Clinical Research, Gastrointestinal Medical Oncology of University of Miami Health Systems in Florida, shed light on the clinical relevance of the approval:

The FDA also approved the immunohistochemistry companion diagnostic, Ventana® CLDN18 (43-14A) RxDx Assay,for use in determining CLND18.2 protein expression in those with gastric or GEJ adenocarcinoma who could be eligible to receive the agent.

10/29: Asciminib in Newly Diagnosed Ph+ Chronic-Phase Chronic Myeloid Leukemia

At the end of the month, asciminib (Scemblix) was awarded accelerated approval from the FDA for use in adult patients with newly diagnosed, Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase (CP-CML) based on data from the phase 3 ASC4FIRST trial (NCT04971226).

Jorge Cortes, MD

Those who received asciminib experienced a major molecular response (MMR) rate of 68% (95% CI, 61%-74%) at 48 weeks vs 49% (95% CI, 42%-56%) with investigator’s choice of TKI, which could have been imatinib (Gleevec), nilotinib (Tasigna), dasatinib (Sprycel), or bosutinib (Bosulif); this translated to a 19% difference between the arms (95% CI, 10%-28%; P < .001). In the imatinib stratum, the MMR rate was 69% (95% CI, 59%-78%) for those in the asciminib arm vs 40% (95% CI, 31%-50%) in the TKI arm (difference, 30%; 95% CI, 17%-42%; P < .001).

“While there are a range of effective TKIs currently available for newly diagnosed patients, clinicians frequently have had to weigh sacrificing either efficacy or tolerability,” Jorge Cortes, MD, director of Georgia Cancer Center, stated in a recent news release. “In the first-of-its-kind ASC4FIRST trial, Scemblix achieved impressive results across all three parameters of efficacy, safety and tolerability versus all standard-of-care TKIs. This Scemblix data has the potential to be practice changing.”

In a past interview, Timothy Hughes, MD, MBBS, FRACP, FRCPA, clinical director of the Precision Cancer Medicine Theme at SAHMRI and consultant hematologist at Royal Adelaide Hospital, discussed the safety and efficacy data from the study:

The next scheduled analysis for the study will focus on the secondary end point of 96-week MMR among others.

Other Noteworthy Decisions:

• The FDA approved the Cologuard Plus test, a next-generation multitarget stool DNA test, for adults who are at least 45 years of age and who are at average risk for colorectal cancer. In the observational BLUE-C trial (NCT04144738), the test showed 93.9% (95% CI, 87.1%-97.7%) overall CRC sensitivity. It also showed a specificity for advanced neoplasia of 90.6% (95% CI, 90.1%-91.0%) and 43.4% (95% CI, 41.3%-45.6%) sensitivity for advanced precancerous lesions at 92.7% (95% CI, 92.2%-93.1%) specificity for nonneoplastic findings or negative colonoscopy.
• The regulatory agency approved the Ion Torrent Oncomine Dx Target Test as a companion diagnostic to identify patients who could receive vorasidenib (Voranigo) tablets. The agent had received approval in August 2024 for use in adult and pediatric patients with grade 2 astrocytoma or oligodendroglioma harboring a susceptible IDH1 or IDH2 mutation after surgery including biopsy, subtotal resection, or gross total resection.

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