Oncology Drugs Approved by the FDA in August 2024

Oncology Drugs Approved by the FDA in August 2024

Throughout the month of August, several cancer therapies have been approved by the FDA for diseases including non-small cell lung cancer (NSCLC), cutaneous T-cell lymphoma, astrocytoma and oligodendroglioma, and endometrial cancer.

Here is a select list of oncology drugs that received FDA approval this past month.

First-Line Amivantamab Plus Lazertinib Receives FDA Approval for EGFR-Positive Advanced NSCLC

This drug combination has been approved for treating locally EGFR-positive advanced or metastatic NSCLC.¹ In the MARIPOSA trial (NCT04487080), amivantamab (Rybrevant) plus lazertinib (Lazcluze) demonstrated superior efficacy compared to standard treatments.² In particular, amivantamab plus lazertinib reduced the risk of progression or death by 30% compared with osimertinib (Tagrisso; HR, 0.70; 95% CI, 0.58-0.85; P < .001). Patients treated with the combination (n = 429) had a median progression-free survival (PFS) of 23.7 months compared with 16.6 months for those treated with osimertinib (n = 429).

Regarding safety, the most common adverse effects reported in at least 20% of patients treated with amivantamab/lazertinib were rash, nail toxicity, infusion-related reactions with amivantamab, musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity.³

FDA Approves Denileukin Diftitox for Relapsed/Refractory Cutaneous T-Cell Lymphoma

The FDA approved denileukin diftitox-cxdl (Lymphir) for the treatment of patients with relapsed/refractory cutaneous T-cell lymphoma who received at least 1 prior systemic therapy.⁴ This approval marks the first indication for this novel immunotherapy and the only treatment for cutaneous T-cell lymphoma that targets the IL-2 receptor.

The FDA approval is based on findings from the phase 3 Pivotal Study 302 (NCT01871727). The objective response rate in this study was 36.2% (95% CI, 25.0-48.7), with a complete response rate of 8.7%. The median time to response with denileukin diftitox was 1.41 months, with approximately 70% of patients achieving a response to therapy after 1 to 2 cycles of the therapy. More than half of patients (52%) had a duration of response of at least 6 months. In addition, 84.4% of patients whose skin was evaluable during the study had a decrease in skin tumor burden, with 12.5% of patients achieving a complete clearing of skin disease.

The prescribing information for denileukin diftitox includes a boxed warning for capillary leak syndrome, and that patients should be monitored for signs and symptoms during treatment. The warning also notes that denileukin diftitox should be withheld until capillary leak syndrome resolves, or permanently discontinue the treatment based on severity.

FDA Approves Vorasidenib to Treat Grade 2 Astrocytoma, Oligodendroglioma With IDH1, IDH2 Mutations

Vorasidenib (Voranigo) has been approved by the FDA to treat adults and pediatric patients aged 12 years and older with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation.⁵ This is the first systemic therapy approved for grade 2 astrocytoma or oligodendroglioma with an IDH1 or IDH2 mutation.

This approval was based on findings from the INDIGO trial (NCT04164901). The hazard ratio for PFS in patients treated with vorasidenib was 0.39 (95% CI, 0.27-0.56; P < .0001). The vorasidenib group did not meet the median time to next intervention compared with 17.8 months in the placebo group (HR = 0.26; 95% CI, 0.15-0.43; P < .0001).

The most common adverse reactions, occurring in at least 15% of patients, included headache, fatigue, musculoskeletal pain, COVID-19 infection, nausea, diarrhea, and seizure. The most common grade 3 or 4 laboratory abnormalities, observed in at least 2% of patients, included increased aspartate aminotransferase levels, increased alanine aminotransferase levels, decreased neutrophil levels, and increase in gamma-glutamyl transpeptidase levels.

Perioperative Durvalumab Receives FDA Approval for Resectable NSCLC

Durvalumab (Imfinzi), an immune checkpoint inhibitor, has been approved by the FDA for use with platinum-containing chemotherapy as neoadjuvant treatment, followed by durvalumab as adjuvant treatment post-surgery, in adults with resectable NSCLC and no known EGFR mutations or ALK rearrangements.^6-8

The approval was based on data from the phase 3 AEGEAN trial (NCT03800134), which demonstrated a statistically significant and clinically meaningful reduction in the risk of recurrence, progression, or death with the chemoimmunotherapy regimen vs chemotherapy alone. The median event-free survival (EFS) was not reached (NR; 95% CI, 31.9-NR) with durvalumab vs 25.9 months (95% CI, 18.9-NR) with placebo (stratified HR, 0.68; 95% CI, 0.53-0.88; P = .004). The 12- and 24-month EFS rates with durvalumab were 73.4% (95% CI, 67.9%-78.1%) and 63.3% (95% CI, 56.1%-69.6%), respectively, vs 64.5% (95% CI, 58.8%-69.6%) and 52.4% (95% CI, 45.4%-59.0%) with placebo.

FDA Expands Approval of Dostarlimab for Advanced, Recurrent Endometrial Cancer

Dostarlimab (Jemperli), an immune checkpoint inhibitor, has had its approval expanded by the FDA to include the treatment of primary advanced or recurrent endometrial cancer.⁹

The expanded approval is supported by data from the phase 3 RUBY trial (NCT03981796), which showed that in the overall population, patients treated with dostarlimab plus chemotherapy experienced a statistically significant improvement in overall survival (OS) compared with those treated with placebo plus chemotherapy (HR, 0.69; 95% CI, 0.54-0.89; 1-sided P = .002).10 The median OS was 44.6 months (95% CI, 32.6–not reached) in the dostarlimab arm vs 28.2 months (95% CI, 22.1-35.6) in the placebo arm.

Regarding safety, the most common adverse effects reported in at least 20% of all patients in the dostarlimab arm included anemia, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, low platelets, increased glucose, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin, abdominal pain, dyspnea, decreased appetite, increased amylase, urinary tract infection and vomiting.

References

1. Rybrevant (amivantamab-vmjw) plus Lazcluze (lazertinib) approved in the U.S. as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer. News release. Johnson & Johnson. August 20, 2024. Accessed August 20, 2024. https://www.investor.jnj.com/news/news-details/2024/RYBREVANT-amivantamab-vmjw-plus-LAZCLUZE-lazertinib-approved-in-the-U.S.-as-a-first-line-chemotherapy-free-treatment-for-patients-with-EGFR-mutated-advanced-lung-cancer/default.aspx
2. Cho BC, Lu S, Felip E, et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med. Published online June 26, 2024. doi:10.1056/NEJMoa2403614
3. FDA approves lazertinib with amivantamab-vmjw for non-small lung cancer. FDA. August 19, 2024. Accessed August 20, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lazertinib-amivantamab-vmjw-non-small-lung-cancer
4. Citius Pharmaceuticals Receives FDA Approval for LYMPHIR™ (denileukin diftitox-cxdl) Immunotherapy for the Treatment of Adults with Relapsed or Refractory Cutaneous T-Cell Lymphoma. News release. Citius Pharmaceuticals, Inc. August 8, 2024. Accessed August 8, 2024. https://www.prnewswire.com/news-releases/citius-pharmaceuticals-receives-fda-approval-for-lymphir-denileukin-diftitox-cxdl-immunotherapy-for-the-treatment-of-adults-with-relapsed-or-refractory-cutaneous-t-cell-lymphoma-302217630.html
5. FDA approves vorasidenib for Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. FDA. August 6, 2024. Accessed August 6, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-or-oligodendroglioma-susceptible-idh1-or-idh2-mutation
6. FDA approves neoadjuvant/adjuvant durvalumab for resectable non-small cell lung cancer. FDA. August 15, 2024. Accessed August 15, 2024. https://www.oncnursingnews.com/view/fda-approves-axatilimab-for-chronic-graft-vs-host-disease
7. Heymach JV, Harpole D, Mitsudomi T, et al. Perioperative durvalumab for resectable non-small-cell lung cancer. N Engl J Med. 2023;389(18):1672-1684. doi:10.1056/NEJMoa2304875
8. FDA advisory committee reviewed Imfinzi for treatment of resectable non-small cell lung cancer based on AEGEAN phase III trial results. News release. AstraZeneca. July 25, 2024. Accessed August 12, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/odac-reviewed-imfinzi-in-resectable-lung-cancer.html
9. FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy. FDA. August 1, 2024. Accessed August 1, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-endometrial-cancer-indication-dostarlimab-gxly-chemotherapy
10. Positive RUBY phase III data show potential for Jemperli (dostarlimab) combinations in more patients with primary advanced or recurrent endometrial cancer. News release. GSK. March 16, 2024. Accessed August 1, 2024. https://www.gsk.com/en-gb/media/press-releases/positive-ruby-phase-iii-data-show-potential-for-jemperli-dostarlimab-combinations-in-more-patients-with-primary-advanced-or-recurrent-endometrial-cancer