FDA NEWS: May 5, 2021 to May 28, 2021

TOP - July 2021 Vol 14, No 4 - FDA Updates

This section provides a brief overview of new cancer drugs and new indications approved by the FDA between May 5, 2021, and May 28, 2021.

NEW DRUGS

Truseltiq Received FDA Approval for Metastatic CCA with FGFR2 Mutation

On May 28, 2021, the FDA granted accelerated approval to infigratinib (Truseltiq: QED Therapeutics, Inc), an oral FGFR1-3 selective inhibitor, for the treatment of adults with previously treated locally advanced or metastatic cholangiocarcinoma (CCA) with a FGFR2 fusion or other rearrangement. The FDA previously granted infigratinib orphan drug and fast-track designations.

The FDA also approved FoundationOne CDx (Foundation Medicine Inc) as a companion diagnostic to help select patients with FGFR2 fusion or other rearrangement who may benefit from infigratinib treatment.

“This is an important milestone for patients diagnosed with FGFR2-fusion-driven cholangiocarcinoma who have recurred after first-line therapy and are in need of targeted options for further treatment,” Susan Moran, MD, MSCE, chief medical officer for QED Therapeutics, Inc, stated in a press release. “Based on the efficacy seen to date, our team believes infigratinib possesses promise for a range of FGFR-driven conditions, including other cancers. We will continue to evaluate its safety and efficacy in these areas of unmet need.”

This approval was based on a phase 2 study of 108 patients with previously treated, unresectable locally advanced or metastatic CCA with an FGFR2 fusion or arrangement as determined by local or central testing. The study’s primary outcomes were overall response rate and duration of response. The overall response rate was 23% and the median duration of response was 5 months.

The most common (≥20%) adverse reactions included increased creatinine, increased phosphate, decreased phosphate, nail toxicity, stomatitis, increased alkaline phosphatase, decreased hemoglobin, increased alanine aminotransferase, dry eye, fatigue, increased lipase, decreased lymphocytes, increased calcium, decreased sodium, alopecia, increased triglycerides, increased aspartate aminotransferase, decreased platelets, increased urate, palmar-plantar erythrodysesthesia syndrome, arthralgia, and dysgeusia.

The recommended infigratinib dose is 125 mg orally once daily on an empty stomach for 21 consecutive days followed by 7 days off therapy, in 28-day cycles.

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Lumakras First FDA-Approved Therapy for Advanced or Metastatic NSCLC with KRAS G12C Mutation

On May 28, 2021, the FDA accelerated the approval of sotorasib (Lumakras; Amgen), an oral KRAS inhibitor of the RAS GTPase family, for the treatment of adults with locally advanced or metastatic non–small-cell lung cancer (NSCLC) associated with KRAS G12C mutation, as determined by an FDA-approved test, after ≥1 systemic therapies. The FDA granted sotorasib orphan drug and breakthrough therapy designations.

This is the first targeted therapy approved by the FDA for cancer associated with any KRAS mutation, a type of mutation that was thought to be resistant to any drug. Approximately 25% of mutations found in patients with NSCLC are KRAS mutations, and approximately 13% of NSCLC-related mutations are KRAS G12C mutations.

KRAS mutations have long been considered resistant to drug therapy, representing a true unmet need for patients with certain types of cancer. Today’s approval represents a significant step toward a future where more patients will have a personalized treatment approach,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence.

This approval was based on a study of 124 patients with locally advanced or metastatic NSCLC and KRAS G12C mutation that progressed after treatment with an immune checkpoint inhibitor and/or platinum-based chemotherapy. The study’s primary outcomes were the objective response rate (ORR) and the duration of response with sotorasib therapy. The ORR was 36%, and the response lasted ≥6 months in 58% of the patients who had a response to sotorasib therapy.

The most common (≥20%) side effects reported with sotorasib include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Treatment with sotorasib should be stopped in patients with symptoms of interstitial lung disease and permanently discontinued if interstitial lung disease is confirmed. In patients with liver damage, sotorasib therapy should be withheld, dose reduced, or permanently discontinued.

Sotorasib is contraindicated with acid-reducing agents, drug inducers or substrates of certain liver enzymes, and drugs that are substrates of the P-glycoprotein.

The recommended daily dose of sotorasib is 960 mg. Continued approval of this indication is contingent on confirmatory data from clinical trials regarding the benefit of this medication.

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Rybrevant First FDA-Approved Therapy for NSCLC with EGFR Exon 20 Insertion Mutations

On May 21, 2021, the FDA accelerated the approval of amivantamab-vmjw (Rybrevant; Janssen/Johnson & Johnson), a bispecific antibody targeting mutations in the EGFR and MET pathways, for adults with non–small-cell lung cancer (NSCLC) that is associated with EGFR exon 20 insertion mutations, as detected by the FDA-approved Guardant360 CDx test, which was approved on the same day as a companion diagnostic for amivantamab. The FDA had granted amivantamab a breakthrough therapy designation for this indication.

Amivantamab is the first drug approved by the FDA for the treatment of patients with NSCLC and EGFR exon 20 insertion mutations. Approximately 2% to 3% of patients with NSCLC have EGFR exon 20 insertion mutations, a group of mutations that causes rapid cell growth. EGFR exon 20 insertion mutations are the third most common type of EGFR mutation.

“With today’s approval, for the first time, patients with non–small-cell lung cancer with EGFR exon 20 insertion mutations will have a targeted treatment option,” said Julia Beaver, MD, Chief of Medical Oncology in the FDA’s Oncology Center of Excellence.

The FDA approved amivantamab based on a study of 81 patients with NSCLC and EGFR exon 20 insertion mutations whose disease progressed during or after platinum-based chemotherapy. The main outcome measured was overall response rate (ORR).

The ORR was 40% and the median duration of response was 11.1 months, including 63% of responses lasting ≥6 months.

The most common side effects of amivantamab include rash, infusion-related reactions, skin infections around the fingernails or toenails, muscle and joint pain, shortness of breath, nausea, fatigue, swelling in the lower legs or hands or face, sores in the mouth, cough, constipation, vomiting, and changes in certain blood tests.

Amivantamab should be withheld if patients have symptoms of interstitial lung disease and permanently discontinued in patients with confirmed disease. Patients taking amivantamab should limit sun exposure during and for 2 months after treatment. Amivantamab may cause vision problems and should not be used in pregnant women.

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NEW INDICATION

Keytruda Received FDA Approval for First-Line Treatment of HER2-Positive Advanced Gastric Cancer

On May 5, 2021, the FDA accelerated the approval of the PD-1 inhibitor pembrolizumab (Keytruda; Merck & Co), in combination with trastuzumab plus fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adult patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

“Today’s approval marks an important milestone, as this is the first time an anti-PD-1 therapy has been approved in combination with anti-HER2 therapy and chemotherapy as a first-line treatment for these patients,” said Roy Baynes, MD, PhD, senior vice president and head of global clinical development at Merck, in a press release.

This approval was based on findings from the prespecified interim analysis of 264 patients with advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma in the ongoing KEYNOTE-811 clinical trial who had not received systemic therapy for metastatic disease. This multicenter, randomized, double-blind, placebo-controlled study randomized the 264 patients in a 1:1 ratio to pembrolizumab 200 mg or to placebo every 3 weeks, in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

The main efficacy measure for this analysis was the overall response rate (ORR). The ORR was 74% (95% confidence interval [CI], 66-82) in the pembrolizumab arm versus 52% (95% CI, 43-61) in the placebo arm, a significant difference (one-sided P value <.0001). The median duration of response was 10.6 months in the pembrolizumab arm versus 9.5 months in the placebo arm.

The adverse reactions reported in this study for pembrolizumab were consistent with the drug’s known safety profile.

The recommended pembrolizumab dose for these indications is 200 mg every 3 weeks or 400 mg every 6 weeks.

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Last modified: August 3, 2021