FDA News: August 24, 2022, and September 30, 2022

TOP - November 2022 Vol 15, No 6 - FDA Updates

This section provides a brief overview of new cancer drugs and new indications approved by the FDA between August 24, 2022, and September 30, 2022.

NEW DRUGS

Lytgobi FDA Approved for Intrahepatic Cholangiocarcinoma with FGFR2 Fusion

On September 30, 2022, the FDA accelerated the approval of futibatinib (Lytgobi; Taiho Oncology), a tyrosine kinase inhibitor, for the treatment of adults with previously treated unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma (CCA) and FGFR2 gene fusion or other rearrangements. Futibatinib received a breakthrough therapy designation for this indication.

This approval was based on results of the multicenter, open-label, single-arm TAS-120-101 clinical trial of 103 patients with unresectable, locally advanced, intrahepatic CCA associated with FGFR2 fusion or other rearrangements.

The primary end points were overall response rate and duration of response. All patients received 20 mg of futibatinib orally until disease progression or unacceptable adverse events. Of the 103 patients, 43 (42%) had a partial response (95% confidence interval [CI], 32-52) to futibatinib, with a median duration of response of 9.7 months (95% CI, 7.6-17.1).

The most common (≥20%) adverse events were nail problems, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, abdominal pain, dry skin, arthralgia, dysgeusia, dry eye, nausea, decreased appetite, urinary tract infection, palmar-plantar erythrodysesthesia syndrome, and vomiting.

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Vegzelma a New Biosimilar FDA Approved for the Treatment of 6 Types of Cancer

On September 28, 2022, the FDA approved bevacizumab-adcd (Vegzelma; Celltrion), a VEGF inhibitor and a biosimilar to bevacizumab (Avastin), for the treatment of metastatic colorectal cancer; recurrent or metastatic nonsquamous non–small-cell lung cancer (NSCLC); recurrent glioblastoma; metastatic renal-cell carcinoma; persistent, recurrent, or metastatic cervical cancer; and epithelial ovarian, fallopian tube, or primary peritoneal cancer. Bevacizumab-adcd is not indicated for the adjuvant treatment of colon cancer.

Bevacizumab-adcd is the fourth biosimilar to bevacizumab to be approved by the FDA. The approval was based on the totality of evidence showing no clinically meaningful differences in efficacy, safety, or pharmacokinetics between bevacizumab-adcd and the reference drug, including the results of a double-blind, randomized phase 3 clinical trial of 689 patients with metastatic or recurrent nonsquamous NSCLC.

In that study, the patients received 15 mg/kg of bevacizumab-adcd intravenously every 3 weeks for up to 6 cycles in the induction phase, followed by every 3 weeks until disease progression in the maintenance phase. The main end point was objective response at 21 weeks. The results showed that bevacizumab-adcd was highly similar to its reference drug in efficacy, safety, and pharmacokinetics.

The most common (>10%) adverse events with bevacizumab-adcd are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.

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Pedmark First Drug Approved for Hearing Loss Prevention in Children with Solid Tumors

On September 20, 2022, the FDA approved sodium thiosulfate (Pedmark; Fennec Pharmaceuticals), an inorganic sodium salt, for risk reduction of hearing loss (ototoxicity) associated with cisplatin treatment in children aged ≥1 month to 18 years with nonmetastatic solid tumors. Sodium thiosulfate received an orphan drug designation for this indication.

The safety and efficacy of sodium thiosulfate when used after cisplatin infusions for ≥6 hours have not been determined; if hearing loss had already occurred, this drug may not reduce its risk after long cisplatin infusions.

This approval was based on the results of 2 phase 3 clinical trials: the multicenter, open-label, randomized controlled SIOPEL 6 and the Clinical Oncology Group (COG) ACCL0431. The SIOPEL 6 study included 114 pediatric patients with standard-risk hepatoblastoma who had received perioperative cisplatin-based chemotherapy. The main end point was the percentage of patients with Brock grade ≥1 hearing loss. The incidence of hearing loss was lower in the sodium thiosulfate plus cisplatin arm than in the cisplatin monotherapy arm (39% vs 68%, respectively; relative risk [RR], 0.58; 95% confidence interval [CI], 0.40-0.83).

The COG ACCL0431 study included 125 pediatric patients with solid tumors who received cumulative cisplatin doses of ≥200 mg/m2, with individual cisplatin doses infused over ≤6 hours. The incidence of hearing loss was lower in the sodium thiosulfate plus cisplatin arm than in the cisplatin monotherapy arm (44% vs 58%, respectively; RR, 0.75; 95% CI, 0.48-1.18).

The most common (≥25% with a between-arms difference of >5% vs cisplatin monotherapy) adverse reactions in both trials were vomiting, nausea, decreased hemoglobin, hypernatremia, and hypokalemia.

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NEW INDICATIONS

Retevmo Receives New FDA Indication for Advanced Solid Tumors with RET Fusion

On September 21, 2022, the FDA accelerated the approval of selpercatinib (Retevmo; Eli Lilly), a selective RET

kinase inhibitor, for the treatment of all locally advanced or metastatic solid tumors with a RET gene fusion in patients whose disease progressed during or after systemic treatment or who have no alternative treatment options.

On the same day, the FDA granted regular full approval to selpercatinib for the treatment of locally advanced or metastatic non–small-cell lung cancer (NSCLC) and RET fusion, as detected by an FDA-approved test, following the FDA’s accelerated approval of this indication on May 8, 2020. Selpercatinib had been previously approved for advanced or metastatic RET-positive thyroid cancer and medullary thyroid cancer.

Also on September 21, the FDA approved the Oncomine Dx Target Test as a companion diagnostic for selpercatinib.

The tumor-agnostic approval of selpercatinib was based on results of the multicenter, multicohort, open-label LIBRETTO-001 clinical trial in 41 patients with RET-positive solid tumors (excluding NSCLC and thyroid cancer) whose disease progressed during or after systemic therapy or who had no alternative treatment options.

“FDA approval of the tumor-agnostic indication underscore[s] the importance of routine, comprehensive genomic testing for patients across a wide variety of tumor types,” said Vivek Subbiah, MD, of The University of Texas MD Anderson Cancer Center, Houston, and a study coinvestigator.

The primary end points were overall response rate (ORR) and duration of response (DOR). For the solid-tumor indication, the ORR was 44% (95% confidence interval [CI], 28-60) with selpercatinib and the DOR was 24.5 months (95% CI, 9.2-not estimable). The tumor types showing responses included pancreatic adenocarcinoma, soft-tissue sarcoma, bronchial carcinoid, cholangiocarcinoma, and colorectal, salivary, breast, ovarian, small intestine, and unknown primary cancers.

The initial approval of selpercatinib for NSCLC was based on results of 144 patients with NSCLC and RET fusion in the LIBRETTO-001 study. The conversion to full approval was based on data for an additional 172 patients, for a total of efficacy data for 316 patients with RET-positive NSCLC. Of 69 treatment-naïve patients with RET-positive NSCLC, the ORR with selpercatinib was 84% (95% CI, 73-92) and the DOR was 20.2 months (95% CI, 13-not estimable). Of 247 patients who had previously received chemotherapy, the ORR with selpercatinib was 61% (95% CI, 55-67) and the DOR was 28.6 months (95% CI, 20-not estimable).

The most common (≥25%) adverse reactions included edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.

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Imfinzi Receives New FDA Indication for Advanced or Metastatic Biliary Tract Cancer

On September 2, 2022, the FDA accelerated the approval of durvalumab (Imfinzi; AstraZeneca), a PD-L1 inhibitor, in combination with gemcitabine and cisplatin, for adults with locally advanced or metastatic biliary tract cancer.

Durvalumab was previously approved for unresectable, stage III non–small-cell lung cancer and for first-line treatment of extensive-stage small-cell lung cancer.

The approval of the new indication was based on results of the randomized, double-blind, placebo-controlled, multiregional TOPAZ-1 clinical trial of 685 patients with histologically confirmed, locally advanced, unresectable or metastatic biliary tract cancer (including 56% of patients with intrahepatic cholangiocarcinoma, 25% with gallbladder cancer, and 19% with extrahepatic cholangiocarcinoma).

The patients were randomized 1:1 to durvalumab plus chemotherapy or to placebo plus chemotherapy and continued treatment until disease progression or unacceptable adverse events.

The median overall survival was 12.8 months in the durvalumab plus chemotherapy arm and 11.5 months in the placebo plus chemotherapy arm (95% confidence interval, 10.1-12.5). The median progression-free survival was 7.2 months with durvalumab and 5.7 months with placebo. The investigator-assessed overall response rate was 27% with durvalumab and 19% with placebo.

The most common (≥20%) adverse events were fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia.

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Pemazyre Receives New Indication for FGFR1-Positive Myeloid/Lymphoid Neoplasms

On August 26, 2022, the FDA accelerated the approval of pemigatinib (Pemazyre; Incyte), a tyrosine kinase inhibitor, for the treatment of relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangements in adults. Pemigatinib received a breakthrough therapy designation for this indication.

Pemigatinib was previously approved for unresectable, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusion or other rearrangements.

The new indication was approved based on results of the multicenter, open-label, single-arm FIGHT-203 clinical trial of 28 adults with relapsed or refractory MLNs and FGFR1 rearrangements. Eligible patients were either not candidates for or had disease relapse after undergoing an allogeneic hematopoietic stem-cell transplant or after receiving disease-modifying therapy.

The primary end point was complete response (CR). A total of 14 of the 18 (78%) patients with chronic-phase disease, regardless of extramedullary disease (EMD) status, achieved a CR (95% confidence interval [CI], 52%-94%). The median time to CR was 104 days (range, 44-435 days), and the median duration of response was not reached (range, 1-988 days). Of the 4 patients with blast-phase disease or without EMD, 2 had a CR (lasting 1-94 days), and 1 of the 3 patients with EMD reached a CR (lasting 64 days).

Of all the 28 patients, including 3 patients without morphologic disease, 22 (79%) patients had a complete cytogenetic response (95% CI, 59%-92%).

The most common (≥20%) adverse events were hyperphosphatemia, nail toxicity, alopecia, stomatitis, diarrhea, dry eye, fatigue, rash, abdominal pain, anemia, constipation, dry mouth, epistaxis, serous retinal detachment, extremity pain, decreased appetite, dry skin, dyspepsia, back pain, nausea, blurred vision, peripheral edema, and dizziness.

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Imbruvica Now Also Indicated for Children with Chronic Graft-versus-Host Disease

On August 24, 2022, the FDA accelerated the approval of ibrutinib (Imbruvica; Pharmacyclics), a Bruton tyrosine

kinase inhibitor, for chronic graft-versus-host disease (GVHD) in pediatric patients aged ≥1 year whose disease did not respond to ≥1 lines of systemic therapy. Concomitantly, the FDA approved a new oral suspension formulation of ibrutinib for use in this patient population.

Ibrutinib was previously approved for adults with chronic GVHD, marginal-zone lymphoma, Waldenström’s macroglobulinemia, chronic or small lymphocytic leukemia, and mantle-cell lymphoma.

The new indication was based on results of the open-label, multicenter, single-arm iMAGINE trial of 47 pediatric patients and young adults aged 1 year to <22 years with moderate or severe chronic GVHD who required additional treatment after ≥1 systemic therapies.

The main end point was overall response rate (ORR) through week 25. The ORR was 60% (95% confidence interval [CI], 44-74). The median duration of response was 5.3 months (95% CI, 2.8-8.8), and the median time from first response to new systemic therapies for chronic GVHD or death was 14.8 months (95% CI, 4.6-not evaluable).

“Now, healthcare professionals have another effective treatment option for both pediatric and adult patients living with this disease after failure of one or more lines of systemic therapy. Additionally, having an oral suspension formulation designed for children is a helpful alternative,” said Paul A. Carpenter, MD, of Seattle Children’s Hospital, WA, and a study investigator.

The most common (≥20%) adverse events were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache.

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Last modified: November 17, 2022