OncLive’s June Roundup of Key FDA Approvals in Oncology

In case you missed it, below is your guide to the key regulatory approvals that were given the green light from the FDA in June 2024, including a snapshot at topline data that supported the decisions and expert insights what these pipeline updates mean for clinical practice.

Imetelstat Offers “First-of-its-Kind” Option for Low- to Intermediate-1 Risk MDS

On June 6, 2024, the FDA approved imetelstat (Rytelo) for the treatment of adults with low- to intermediate-1–risk myelodysplastic syndrome and transfusion-dependent anemia requiring 4 or more red blood cell (RBC) units over 8 weeks who have not responded, have lost response to, or are not eligible to receive erythropoiesis-stimulating agents (ESAs).

Data from the phase 3 IMerge study (NCT02598661) indicated that patients who received the oligonucleotide telomerase inhibitor (n = 118) had an RBC transfusion independence (RBC-TI) rate of 39.8% (95% CI, 30.9%-49.3%) vs 15% (95% CI, 7.1%-26.6%) in those given placebo (n= 59; P < .001). The 16-, 24-, and 52-week RBC-TI rates with imetelstat were 31.4% (95% CI, 23.1%-40.5%), 28.0% (95% CI, 20.1%-37.0%), and 13.6% (95% CI, 8.0%-21.1%), respectively, vs 6.7% (95% CI, 1.9%-16.2%), 3.3% (95% CI, 0.4%-11.5%), and 1.7% (95% CI, 0%-8.9%) with placebo, respectively.

“With imetelstat’s approval for patients who are transfusion dependent, with lower-risk MDS, we finally have another tool in our tool[box]. We have really had a drug desert that has occurred over a decade in new treatments for patients with lower-risk MDS,” Mikkael A. Sekeres, MD, said in an interview with OncLive®. “For those who have anemia, we typically start with ESAs, and then if they have a deletion 5q abnormality, we’ll move to lenalidomide [Revlimid.] We have had a recent approval of luspatercept-aamt [Reblozyl] both in the up-front and subsequent setting, after patients have been exposed to ESAs, but that drug really works predominantly in [those] who have a spliceosome mutation or ring sideroblasts. So, for patients who don’t have a spliceosome mutation or ring sideroblasts or deletion 5q, the only thing we have left are hypomethylating agents [HMAs]. With imetelstat, we have another option to treat patients before or after they’re exposed to HMAs.”

Selpercatinib Wins Full Approval for RET+ Thyroid Cancer

On June 12, 2024, selpercatinib (Retevmo) received regular approval for use in adult and pediatric patients at least 2 years of age with advanced or metastatic RET fusion–positive thyroid cancer who require systemic therapy and who are refractory to radioactive iodine, if appropriate.

The full approval was based, in part, on findings from the phase 1/2 LIBRETTO-001 trial (NCT03157128), in which the RET inhibitor led to an overall response rate (ORR) of 85% (95% CI, 71%-94%) in those who received prior treatment (n = 41) and 96% (95% CI, 79%-100%) in those who were naive to systemic therapy (n = 24). The median duration of response (DOR) in these respective subsets was 26.7 months (95% CI, 12.1-not evaluable [NE]) and NE (95% CI, 42.8-NE). Additional efficacy data showed that selpercatinib induced an ORR of 60% (95% CI, 26%-885) in pediatric and young adult patients with thyroid cancer harboring RET fusions who were treated during the phase 1/2 LIBRETTO-121 trial (NCT03899792; n = 10) with most (83%) experiencing a DOR of at least 1 year.

In a recent interview, Lori Wirth, MD, associate professor of medicine at Harvard Medical School and medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital, further discussed the significance of the approval. “This is a major landmark for patients with RET-driven cancers,” she underscored.

Repotrectinib Awarded Accelerated Approval for NTRK+ Solid Tumors

The next day, on June 13, 2024, the regulatory agency granted accelerated approval to repotrectinib (Augtyro) for adult and pediatric patients at least 12 years of age with solid tumors harboring an NTRK gene fusion, that are locally advanced or metastatic or where surgical resection is likely to result in severe morbidity, and that have progressed following treatment or have no satisfactory alternative options.

The decision was based on data from the phase 1/2 TRIDENT-1 study (NCT03093116), in which the agent induced confirmed ORRs of 58% (95% CI, 41%-73%) and 50% (95% CI, 35%-65%) by blinded independent central review and RECIST 1.1 criteria in patients who were naive (n = 40) or who had prior exposure (n = 48) to a TKI. The median DOR in these respective groups was NE (95% CI, NE-NE) and 9.9 months (95% CI, 7.4-13.0).

“NTRK fusion–positive tumors can present challenges in the clinical setting, which is why it is important that we have additional treatment options for these patients,” Alexander Drilon, MD, TRIDENT-1 global trial lead and chief of the early drug development service at Memorial Sloan Kettering Cancer Center, stated in press release. “The FDA approval of repotrectinib adds an important tool to our toolbox, offering oncologists a next-generation TKI that can be used across a broad range of NTRK fusion–positive solid tumors for both TKI-naive and TKI-pretreated patients.”

Durvalumab Plus Chemo Scores Approval for dMMR Endometrial Cancer

In June 14, 2024, the FDA approved durvalumab (Imfinzi) in combination with carboplatin plus paclitaxel,followed by durvalumab monotherapy, for adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient.

Findings from the phase 3 DUO-E trial (NCT04269200) showed that durvalumab paired with chemotherapy (n = 46) led to a median progression-free survival (PFS) that was not yet reached (NR; 95% CI, NR-NR) by investigator assessment and RECIST 1.1 criteria vs 7 months (95% CI, 6.7-14.8) with chemotherapy alone (n = 49) in this subset of patients, translating to a 58% reduction in the risk of disease progression or death (HR, 0.42; 95% CI, 0.22-0.80).

“DUO-E results support the addition of durvalumab to platinum-based chemotherapy as a new treatment option for patients with endometrial cancer, with the greatest benefit for dMMR disease,” Els Van Nieuwenhuysen, MD, a gynecologist oncologist at UZ Leuven in Belgium, said in a presentation of the data shared during the 2024 ESMO Gynecological Cancers Congress.

Additional data indicated that the combination of durvalumab plus chemotherapy, followed by maintenance durvalumab with or without olaparib (Lynparza), resulted in improved ORR, DOR, and time to treatment discontinuation vs chemotherapy alone, followed by maintenance placebo, in this patient subset and the overall population.

First BiTE Approved for Consolidation Treatment Irrespective of MRD Status in CD19+ B-ALL

On the same day, the regulatory agency also approved blinatumomab (Blincyto) for use in adult and pediatric patients aged 1 month or older with CD19-positive, Philadelphia chromosome–negative, B-cell precursor acute lymphoblastic leukemia in the consolidation phase, regardless of measurable residual disease status.

The addition of blinatumomab to multiphase consolidation chemotherapy (n = 112) provided a superior overall survival (OS) benefit than chemotherapy alone (n = 112) in this population, according to data from the phase 3 ECOG-ACRIN E1910 study (NCT02003222). The OS rates at 3 years in these respective arms were 84.8% (95% CI, 76.3%-90.4%) and 69% (95% CI, 58.7%-77.2%). At a median follow-up of 4.5 years, the 5-year OS rates were 82.4% (95% CI, 73.7%-88.4%) and 62.5% (95% CI, 52.0%-71.3%). The hazard ratio for OS was 0.44 (95% CI, 0.23-0.76; P = .003).

“In the E1910 study, blinatumomab reduced risk of death and showed a remarkable improvement in OS,” Selina M. Luger, MD, professor of hematology-oncology at the University of Pennsylvania’s Perelman School of Medicine and Abramson Cancer Center, chair of the ECOG-ACRIN Leukemia Committee and an investigator on the study,” stated in a press release. “This approval redefines the standard of care for patients with B-ALL and provides them with a more effective treatment option than standard chemotherapy alone.”

Pembrolizumab Plus Chemo Snags Approval for Advanced/Recurrent Endometrial Carcinoma

On June 17, 2024, the FDA approved pembrolizumab (Keytruda) plus carboplatin/paclitaxel, followed by pembrolizumab monotherapy, for use in adult patients with primary advanced or recurrent endometrial carcinoma.

Findings from the phase 3 KEYNOTE-868 study (NCT03914612; NRG-GY018) indicated that in the dMMR population, pembrolizumab plus chemotherapy (n = 110) led to a median PFS that was NR (95% CI, 30.7-NR) vs 6.5 months (95% CI, 6.4-8.7) with placebo plus chemotherapy (n = 112), translating to a 70% reduction in the risk of disease progression or death (HR, 0.30; 95% CI, 0.19-0.48; P < .0001). In the subset of patients with mismatch repair–proficient disease, those in the pembrolizumab arm (n = 294) experienced a median PFS of 11.1 months (95% CI, 8.7-13.5) vs 8.5 months (95% CI, 7.2-8.8) in the placebo arm (n = 294), translating to a 40% reduction in the risk of disease progression or death (HR, 0.60; 95% CI, 0.46-0.78; P < .0001).

“[We] had 3 or 4 randomized phase 3 trials evaluating the role of immunotherapy in combination with chemotherapy followed by immunotherapy monotherapy for patients with advanced endometrial cancer,” Eirwen M. Miller, MD, a gynecologic oncologist at Allegheny Health Network West Penn Hospital in Pittsburgh, Pennsylvania, said in an interview with OncLive. “In each of those trials—NRG-GY018, RUBY, AtTEnd, and DUO-E—we saw a statistically significant and incredibly clinically meaningful survival benefit when adding immunotherapy to standard chemotherapy. This [occurred] particularly in the dMMR cohorts.”

R. Wendel Naumann, MD, a gynecologic oncologist at Atrium Health Levine Cancer Institute in Charlotte, North Carolina, also discussed the role of frontline maintenance therapy for patients with endometrial cancer, which patients are likely to benefit from the phase 3 RUBY (NCT03981796) and KEYNOTE-868 regimens, and more in a podcast episode.

Adagrasib/Cetuximab Combo Wins Accelerated Approval in KRAS G12C+ CRC

On June 21, 2024, the combination of adagrasib (Krazati) and cetuximab (Erbitux) received accelerated approvalfrom the FDA for use in adult patients with KRAS G12C–mutated colorectal cancer who previously received treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

Treatment with the doublet (n = 94) led to an ORR of 34% (95% CI, 25%-45%), which was comprised entirely of partial responses. The median DOR was 5.8 months (95% CI, 4.2-7.6), with 31% of patients continuing to respond for at least 6 months. The most frequent adverse effects occurring in at least 20% of patients were rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, cough, dizziness, constipation, and peripheral neuropathy.

In a recent interview with OncLive, Scott Kopetz, MD, PhD, FACP, professor of gastrointestinal medical oncology and associate vice president of Translational Integration at The University of Texas MD Anderson Cancer Center, in Houston, discussed the rationale for evaluating adagrasib plus cetuximab in KRYSTAL-1.

First Bispecific Antibody Gets Approved for Relapsed/Refractory Follicular Lymphoma

On June 26, 2024, the FDA granted accelerated approval to epcoritamab-bysp (Epkinly) for the treatment of adult patients with relapsed or refractory follicular lymphoma after 2 or more lines of systemic therapy.

The T-cell–engaging bispecific antibody induced an ORR of 82% (95% CI, 74.1%-88.2%) in the primary efficacy population (n = 127) of the phase 1/2 EPCORE NHL-1 trial (NCT03625037; Study GCT3013-01), with 60% (95% CI, 50.8%-68.4%) of patients achieving a complete response and 22% (95% CI, 15.2%-30.3%) experiencing a partial response. The median time to first response was 1.4 months (range, 1-3). Moreover, with a median follow-up of 14.8 months in those who responded to epcoritamab, the median DOR was NR (95% CI, 13.7-NR), and the Kaplan Meier–estimated 12-month DOR rate was 68.4% (95% CI, 57.6%-77.0%).

“Patients with relapsed or refractory follicular lymphoma face significant treatment challenges, and there is currently no clear standard of care treatment available across practice settings,” Jeff Sharman, MD, disease chair of Hematology Research at Sarah Cannon Research Institute of Willamette Valley Cancer Institute in Eugene, Oregon, stated in a press release. “The responses observed in the follicular lymphoma cohort of the EPCORE NHL-1 clinical trial, as well as in patients with relapsed or refractory diffuse large B-cell lymphoma from the trial, show the potential of [epcoritamab] to serve as an important treatment option for these patients.”

Novel Formulation to Treat Breast and Ovarian Cancers Gets Green Light

Closing out the month, on June 28, 2024, the FDA approved a new drug application for Tepylute (formerly SH-105), which is a ready-to-dilute formulation to treat adenocarcinoma of the breast and ovary. The drug is a liquid formulation of the standard-of-care agent, thiotepa. This formulation addresses the shortcomings of the current lyophilized powder formulation in that it eliminates the need for complex and time-consuming reconstitution and permits consistent accuracy with regard to dosing.

“We have taken a vital oncology drug and made it easier for oncology clinics and hospitals to use, while also reducing medical personnel exposure to a hazardous drug,” Sharon Cunningham, chief executive officer and co-founder of Shorla Oncology, stated in a news release.

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