FDA NEWS: August 13, 2021 to September 22, 2021

TOP - November 2021 Vol 14, No 7 - FDA Updates

This section provides a brief overview of new cancer drugs and new indications approved by the FDA between August 13, 2021, and September 22, 2021.

NEW DRUGS

Tivdak First Antibody–Drug Conjugate FDA Approved for Patients with Recurrent or Metastatic Cervical Cancer

On September 20, 2021, the FDA accelerated the approval of tisotumab vedotin-tftv (Tivdak; Seagen), a tissue factor–directed antibody and microtubule inhibitor conjugate, for the treatment of women with recurrent or metastatic cervical cancer whose disease progressed during or after chemotherapy.

This approval was based on an open-label, multicenter, single-arm clinical trial of 101 patients with recurrent or metastatic cervical cancer who had received ≤2 systemic regimens that included ≥1 platinum-based chemotherapy regimens in the recurrent or metastatic setting. The patients received intravenous infusion of tisotumab vedotin 2 mg/kg every 3 weeks until disease progression or unacceptable adverse events.

The main efficacy measures were confirmed objective response rate (ORR) and duration of response (DOR). The ORR was 24% (95% confidence interval [CI], 15.9%-33.3%), with a median DOR of 8.3 months (95% CI, 4.2-not reached).

The most common (≥25%) adverse events were reduced hemoglobin, fatigue, reduced lymphocytes, nausea, peripheral neuropathy, alopecia, epistaxis, conjunctival adverse reactions, hemorrhage, reduced leukocytes, increased creatinine, dry eye, increased prothrombin international normalized ratio, prolonged activated partial thromboplastin time, diarrhea, and rash. The prescribing information of tisotumab vedotin includes a boxed warning about ocular adverse events.

Continued approval for this indication may be contingent on confirmatory data from a clinical trial.

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Exkivity Novel Oral Targeted Therapy Approved for Metastatic NSCLC with EGFR Exon 20 Insertion Mutations

On September 15, 2021, the FDA accelerated the approval of mobocertinib (Exkivity; Takeda), an oral kinase inhibitor, for adults with locally advanced or metastatic non–small-cell lung cancer (NSCLC) and EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease progressed during or after platinum-based chemotherapy. Mobocertinib received breakthrough therapy and orphan drug designations for this indication.

On the same day, the FDA also approved the Oncomine Dx Target Test (Life Technologies Corporation) as a companion diagnostic test for the identification of candidates for mobocertinib therapy.

The FDA approved mobocertinib based on Study 101, an international, nonrandomized, open-label, multicohort clinical trial of 114 patients with locally advanced or metastatic NSCLC and EGFR exon 20 insertion mutations, whose disease progressed during or after platinum-based chemotherapy. Patients received oral mobocertinib 160 mg daily, until disease progression or intolerable adverse events.

The main efficacy measures were overall response rate (ORR) and response duration. The ORR was 28%, with a median response duration of 17.5 months.

The most common (>20%) adverse reactions were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain. Mobocertinib was approved with boxed warnings about risk for corrected QT prolongation and torsades de pointes, interstitial lung disease or pneumonitis, cardiac adverse reactions, and diarrhea.

Continued approval of this indication may be contingent on confirmatory data from a clinical trial.

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Welireg FDA Approved for 3 Tumor Types Associated with von Hippel-Lindau Disease

On August 13, 2021, the FDA approved belzutifan (Welireg; Merck), an oral hypoxia-inducible factor inhibitor, for the treatment of adults with von Hippel-Lindau (VHL) disease that is associated with 1 of 3 tumor types that are not requiring immediate surgery, including renal-cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET).

The FDA approved belzutifan based on the ongoing Study 004, an open-label clinical trial involving 61 patients with VHL-associated RCC diagnosed based on a VHL germline alteration and at least 1 measurable solid tumor localized to the kidney; in addition, 24 patients had VHL-associated CNS hemangioblastomas and 12 patients had pNET. All the patients received belzutifan 120 mg once daily until disease progression or unacceptable adverse events. The primary end point was overall response rate (ORR). The secondary end points included duration of response (DOR) and time to response.

The ORR was 49% (95% confidence interval [CI], 36%-62%) among patients with VHL-associated RCC. The patients who had a response were followed for ≥18 months. The median DOR was not reached, and 56% of responders had a response lasting ≥12 months, with a median time to response of 8 months. Furthermore, the ORR was 63% in the 24 patients with VHL-associated CNS hemangioblastomas, and 83% in the 12 patients with VHL-associated pNET. The median DOR among these 2 cohorts was not reached; 73% and 50% of patients, respectively, had a response lasting ≥12 months.

The most common (≥20%) adverse reactions with belzutifan were decreased hemoglobin level, anemia, fatigue, increased creatinine, headache, dizziness, increased glucose level, and nausea. Anemia and hypoxia linked to belzutifan use can be severe. Anemia occurred in 90% of the patients, including 7% grade 3 anemia.

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NEW INDICATIONS

Jakafi a New Treatment Option for Chronic GVHD

On September 22, 2021, the FDA approved a new indication for ruxolitinib (Jakafi; Incyte) for the treatment of patients aged ≥12 years with chronic graft-versus-host disease (GVHD) after 1 or 2 lines of systemic therapy. Ruxolitinib received an orphan drug designation for this indication.

Ruxolitinib was previously approved for several indications, including the treatment of patients with myelofibrosis and polycythemia vera. This new approval was based on the REACH-3 study, a randomized, open-label, multicenter clinical trial of ruxolitinib versus best available therapy for corticosteroid-refractory chronic GVHD after allogeneic stem-cell transplant.

The study included 329 patients who were randomized in a 1:1 ratio to ruxolitinib 10 mg twice daily or to best available therapy. The major efficacy outcome was overall response rate (ORR) through cycle 7 of day 1. The ORR was 70% (95% confidence interval [CI], 63%-77%) with ruxolitinib versus 57% (95% CI, 49%-65%) with best available therapy. The median duration of response was 4.2 months with ruxolitinib and 2.1 months with best available therapy. The median time from first response to death or initiation of new systemic therapy for chronic GVHD was 25 months versus 5.6 months, respectively.

The most common (>35%) hematologic adverse events with ruxolitinib in this study were anemia and thrombocytopenia. The most common (≥20%) nonhematologic adverse reactions were infections and viral infection.

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Cabometyx Approved for Differentiated Thyroid Cancer

On September 17, 2021, the FDA accelerated the approval of a new indication for cabozantinib (Cabometyx; Exelixis) for the treatment of patients aged ≥12 years with locally advanced or metastatic differentiated thyroid cancer that has progressed after VEGFR-targeted therapy and who are ineligible for, or whose disease is refractory to, radioactive iodine. The FDA granted cabozantinib breakthrough therapy and orphan drug designations for this indication.

Cabozantinib was previously approved for several indications. This new approval was based on the COSMIC-311 study, a multicenter clinical trial of patients with locally advanced or metastatic differentiated thyroid cancer that had progressed after VEGFR-targeted therapy and who were ineligible for or refractory to radioactive iodine.

Patients were randomized in a 2:1 ratio to cabozantinib 60 mg orally once daily or to placebo and best supportive care until disease progression or intolerable adverse events. The primary efficacy measures were progression-free survival (PFS) in the intent-to-treat population and overall response rate (ORR) in the first 100 randomized patients.

Cabozantinib significantly reduced the risk for disease progression or death versus placebo. The median PFS was 11 months with cabozantinib versus 1.9 months with placebo. The ORR was 18% versus 0%, respectively.

The most common (≥25%) adverse events in the study were diarrhea, palmar-plantar erythrodysesthesia, fatigue, hypertension, and stomatitis.

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Last modified: November 12, 2021