OncLive’s August Roundup of Key FDA Approvals in Oncology

Below is your guide to the treatment options that were given the green light by the FDA in August 2024. The recap comprises topline findings that support the regulatory decisions and features expert insights on what they mean for their respective paradigms.

Dostarlimab/Chemo Indication Expands in Endometrial Cancer

On the first of the month, the FDA approved dostarlimab-gxly (Jemperli) plus carboplatin and paclitaxel, followed by dostarlimab monotherapy, for use in adult patients with primary advanced or recurrent endometrial cancer. This decision broadens the previous indication for dostarlimab plus chemotherapy to include those with mismatch repair–proficient tumors.

The expanded indication is based on findings from part 1 of the phase 3 RUBY trial (NCT03981796). In the overall population, dostarlimab plus chemotherapy (n = 245) led to a median overall survival (OS) of 44.6 months (95% CI, 32.6-not reached [NR]) vs 28.2 months (95% CI, 22.1-35.6) with placebo plus chemotherapy (n = 249), translating to a 31% reduction in the risk of death (HR, 0.69; 95% CI, 0.54-0.89; 1-sided P = .002). Moreover, the median progression-free survival (PFS) in the respective arms was 11.8 months (95% CI, 9.6-17.1) and 7.9 months (95% CI, 7.6-9.5), respectively (HR, 0.64; 95% CI, 0.51-0.80; 1-sided P < .0001).

In an exclusive interview with OncLive^®, Dana M. Chase, MD, associate professor of obstetrics and gynecology in the Division of Gynecologic Oncology at the University of California, Los Angeles, discussed the significance of the approval in this population:

In another interview, Matthew Powell, MD, the Ira C. and Judith Gall Distinguished Professor of Obstetrics and Gynecology, Division of Gynecologic Oncology, Washington University School of Medicine in St. Louis, Missouri, detailed the OS benefits observed with the combination of dostarlimab and chemotherapy, highlighting the improvements seen in the overall, mismatch repair–deficient, and mismatch repair–proficient populations.

Afami-Cel Wins Accelerated Approval for Advanced Synovial Sarcoma

On August 2, 2024, the regulatory agency awarded accelerated approval to afamitresgene autoleucel (afami-cel; Tecelra) for use in adult patients with unresectable or metastatic synovial sarcoma who have received prior chemotherapy; are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive; and whose tumors express MAGE-A4. Moreover, 510(k) clearance was given to the SeCore™ CDx HLA A Sequencing System for use as a companion diagnostic for the therapy.

The indication is based on overall response rate (ORR) and duration of response (DOR) data from cohort 1 of the phase 2 SPEARHEAD-1 trial (NCT04044768). Patients who received the agent (n = 44) experienced an ORR of 43% by independent review committee (IRC) assessment, which comprised a complete response (CR) rate of 4.5%. The median DOR was 6 months (95% CI, 4.6-NR), and the 12-month DOR rate was 39%.

In a prior press release, Sandra P. D’Angelo, MD, lead study author, sarcoma oncologist and cellular therapist at Memorial Sloan Kettering Cancer Center in New York, New York, underscored: “These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy. The publication of [these] data further validates the potential of afami-cel to offer a new tool to address the unmet needs of people diagnosed with these often-devastating diseases.”

With this decision, afami-cel is the first engineered cell therapy approved for a solid tumor and the first new therapeutic option in over a decade for synovial sarcoma, according to the drug developer, Adaptimmune Therapeutics, plc.

Vorasidenib Becomes First Targeted Therapy Approved for IDH1/2+ Low-Grade Glioma

On August 6, 2024, the FDA approved vorasidenib (Voranigo) for use in adult and pediatric patients at least 12 years of age with grade 2 astrocytoma or oligodendroglioma and a susceptible IDH1 or IDH2 mutation after surgery.

In the phase 3 INDIGO study (NCT04164901), the median PFS with vorasidenib (n = 168) was 27.7 months (95% CI, 17.0-not estimated) vs 11.1 months (95% CI, 11.0-13.7) with placebo (n = 163), translating to a 61% reduction in the risk of disease progression or death (HR, 0.39; 95% CI, 0.27-0.56; P < .001).

In a prior interview with OncLive, Patrick Y. Wen, MD, director of the Center for Neuro-Oncology and institute physician at Dana-Farber Cancer Institute in Boston, Massachusetts, further described the evaluation of the agent in the INDIGO trial in a past interview with OncLive:

“It’s a very exciting time in the field of neuro-oncology. This is the first time that we’ve seen a targeted therapy be of substantial value in this patient population, and in infiltrating gliomas more broadly,” Rimas V. Lukas, MD, a neuro-oncologist at Northwestern Medicine and associate professor of Neurology, Northwestern University Feinberg School of Medicine, in Chicago, Illinois, told OncLive in another interview.

“The overall tolerability of this therapeutic easily lends itself to potential combinations with other agents. It’ll be the job of investigators to be thoughtful about what the optimal pairing will be," he added. "That will involve a lot of preclinical work that will hopefully spur rapid translation into the clinical realm.”

Denileukin Diftitox Gets Green Light for Relapsed/Refractory Cutaneous T-Cell Lymphoma

A couple of days later, on August 8, 2024, the regulatory agency approved denileuken diftitox-cxdl (Lymphir) for use in patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) following at least previous 1 systemic therapy based on data from the phase 3 Study 302 (NCT01871727) in which the agent (n = 69) induced an ORR of 36.2% (95% CI, 25.0%-48.7%) by IRC assessment. The median time to response was 1.41 months and 52.0% of patients experienced a duration of response that lasted for at least 6 months.

The biologics license application (BLA) for the drug in this population was first submitted in October 2022 and accepted for review in December 2022. In July 2023, the regulatory agency issued a complete response letter to the application, requesting that Citius Pharmaceuticals, Inc., the drug developer, include stronger product testing and additional controls that had been agreed on during the review of the market application. The BLA was resubmitted in February 2024 and accepted for review again in March 2024.

“As a treating oncologist, I have seen the profound negative effect on the quality of life in patients with relapsed/refractory CTCL. Given the long-term nature of the disease, pruritus, ulceration of the tumors, and secondary pyogenic skin infection, it is vital to get this skin involvement under control,” Francine Foss, MD, professor of Hematology and director of the Multidisciplinary T-cell Lymphoma Program at Yale Cancer Center, New Haven, Connecticut, stated in a news release. “Lymphir is the first therapeutic option in many years to offer hope of reducing skin disease, bringing us one step closer to filling the need for [patients with] CTCL, particularly those that are not able to complete or continue prior therapies.”

Axatilimab Receives Approval for Chronic Graft-vs-Host Disease

On August 14, 2024, the FDA approved axatilimab-csfr (Niktimvo) for use in adult and pediatric patients weighing at least 40 kg who have chronic graft-vs-host disease and have progressed on at least 2 previous lines of systemic treatment. In the phase 2 AGAVE-201 study (NCT04710576), the colony-stimulating factor-1 receptor­–blocking antibody given at the recommended phase 2 dose led (n = 79) to an ORR of 75% (95% CI, 64%-84%) through day 1 of cycle 7. The median time to response was 1.5 months (range, 0.9-5.1) and the median DOR was 1.9 months (95% CI, 1.6-3.5).

Earlier this year, a panel of experts comprised of Yi-Bin Chen, MD, director of the Transplant and Cell Therapy Program at Massachusetts General Hospital and professor of medicine at Harvard Medical School; Mitchell Horwitz, MD, professor of medicine and director of the Adult Blood and Marrow Transplant Program at Duke University; Corey Cutler, MD, MPH, FRCPC, director of the Stem Cell Transplant Program at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School; and Hannah Choe, MD, assistant professor and director of the GVHS program at Ohio State University; shared insights on emerging agents in GVHD as part of an OncLive Peer Exchange program. The panel reviewed the data shared during the 2023 ASH Annual Meeting and projected that axatilimab would be a promising addition to the chronic GVHD treatment arsenal, with unique mechanisms of action. However, they also acknowledged the need for careful consideration of its intravenous delivery and potential toxicities.

In an OncLive Rapid Readout released in March 2024, Zachariah DeFilipp, MD, of Massachusetts General Hospital, walked through safety and efficacy data from the AGAVE-201 study and its clinical implications.

Perioperative Durvalumab Plus Chemotherapy Snags Approval for Resectable NSCLC

A day later, the regulatory agency gave the green light to durvalumab (Imfinzi) paired with platinum-containing chemotherapy as neoadjuvant treatment, followed by adjuvant durvalumab monotherapy after surgery, in adult patients with resectable non–small cell lung cancer (NSCLC) and no known EGFR mutations or ALK rearrangements.

The decision was based on data from the phase 3 AEGEAN trial (NCT03800134) which showed that the median event-free survival (EFS) was NR (95% CI, 31.9-NR) with the durvalumab regimen (n = 400) vs 25.9 months (95% CI, 18.9-NE) with neoadjuvant placebo plus chemotherapy followed by surgery and adjuvant placebo monotherapy (n = 402; HR, 0.68; 95% CI, 0.53-0.88; P = .0039). Moreover, the pathologic complete response rate was 17% (95% CI, 13%-21%) in the durvalumab arm vs 4.3% (95% CI, 2.5%-7%) in the placebo arm.

In a recent interview, Brendon M. Stiles, MD, associate director of Surgical Oncology; chief of the Divisions of Thoracic Surgery and Surgical Oncology; and professor of cardiothoracic surgery in the Department of Cardiothoracic and Vascular Surgery at Montefiore Einstein Comprehensive Cancer Center, in the Bronx, New York, discussed the implications of the FDA approval:

Notably, the decision followed an Oncologic Drugs Advisory Committee meeting where the data from the trial were discussed, as well as the clinical trial design to determine benefit from phase of treatment. The committee voted 11 to 0 that the agency should require adequate within-trial assessment of contribution of treatment phase in new trial design proposals for perioperative regimens in resectable NSCLC.

“In the case of the AEGEAN and KEYNOTE-671 [NCT03425643] regimens, at this point, the KEYNOTE-671 [data] are a bit more mature [showing both an improvement in EFS and OS]; [it] is wonderful that we have a regimen that has done that for patients. [However,] we also have a lot of experience [using] the phase 3 PACIFIC trial [NCT02125461] regimen with 1 year of adjuvant durvalumab—that’s also something that we have developed a significant degree of comfort with,” John V. Heymach, MD, PhD, chair of and a professor in the Department of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston and David Bruton, Jr Chair in Cancer Research and a professor in the Department of Cancer Biology, said in an interview with OncLive. “Keep in mind, for the AEGEAN trial, approximately 70% of patients had stage III disease, which is a population that overlaps with the population from PACIFIC," he added. "Choice of multiple effective regimens is good, and as always physicians and patients will review the data and select the regimen accordingly.”

Amivantamab/Lazertinib Combo Gets Approval for EGFR+ NSCLC

To close out the month, the regulatory agency approved amivantamab-vmjw (Rybrevant) paired with lazertinib (Lazcluze) for the frontline treatment of adult patients with locally advanced or metastatic NSCLC and EGFR exon 19 deletions or exon 21 L858R substitution mutations. With this decision, the doublet represents the first and only frontline, multitargeted, chemotherapy-free combination to showcase superiority vs osimertinib (Tagrisso) approved for use in this population, according to Johnson & Johnson.

In the phase 3 MARIPOSA study (NCT04487080), amivantamab plus lazertinib (n = 429) led to a median PFS of 23.7 months (95% CI, 19.1-27.7) vs 16.6 months (95% CI, with osimertinib (n = 429), translating to a 30% reduction in the risk of disease progression or death (HR, 0.70; 95% CI, 0.58-0.85; P < .001).

In an interview with OncLive, Joshua K. Sabari, MD, an associate professor in the Department of Medicine of New York University (NYU) Grossman School of Medicine and medical director of Thoracic Medical Oncology at NYU Langone Health’s Perlmutter Cancer Center, highlighted the implications of the FDA approval of amivantamab plus lazertinib:

In an OncLive Peer Exchange that aired in July 2024, Benjamin Levy, MD, of Johns Hopkins Medicine, in Washington, DC, discussed the rationale behind using the frontline regimen in EGFR-mutated NSCLC and reviewed the efficacy and safety data from MARIPOSA with the rest of the panel, which included Mark Socinski, MD, of AdventHealth Cancer Institute, in Orlando Florida, Zosia Piotrowska, MD, MHS, of Massachusetts General Hospital, Helena A. Yu, MD, of Memorial Sloan Kettering, and Julia Rotow, MD, of Dana-Farber Cancer Institute:

Alexander Spira, MD, PhD, FACP, FASCO, of Virginia Cancer Specialists, also hosted an OncLive Rapid Readouts program on data from a secondary analysis of MARIPOSA, which examined first-line amivantamab/lazertinib vs osimertinib in patients with EGFR-mutated advanced NSCLC with biomarkers of high-risk disease.