FDA NEWS: September 20, 2021 and October 29, 2021

TON - December 2021 Vol 14, No 6

This section provides a brief overview of new cancer drugs and new indications approved by the FDA between September 20, 2021, and October 29, 2021.


NEW DRUGS

FDA Approves Scemblix for 2 Indications in CML

On October 29, 2021, the FDA granted accelerated approval to asciminib (Scemblix; Novartis) for the treatment of patients with Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) in chronic phase, previously treated with ≥2 tyrosine kinase inhibitors (TKIs). The drug was also granted a full approval for the treatment of patients with Ph+ CML in chronic phase with a T315I mutation.

The approvals are based on the phase 3 ASCEMBL trial, which included patients with Ph+ CML in chronic phase who previously received ≥2 TKIs, and the phase 1 CABL001X2101 trial, which included patients with Ph+ CML in chronic phase harboring a T315I mutation.

ASCEMBL included 233 patients randomized in a 2:1 ratio to receive asciminib at a twice-daily dose of 40 mg (N = 57) or bosutinib (Bosulif; Pfizer) at a once-daily dose of 500 mg (N = 76), with treatment continuing until intolerable toxicity or treatment failure.

At 24 weeks, the major molecular response (MMR) rate was 25% in the asciminib arm compared with 13% in the bosutinib arm. The complete cytogenetic response rates at 24 weeks were 41% and 24%, respectively. At 48 weeks, the MMR rate was 29% with asciminib versus 13% with bosutinib.

Forty-five patients enrolled in the multicenter, open-label CABL001X2101 trial were administered asciminib at a twice-daily dose of 200 mg, with treatment continuing until intolerable toxicity or treatment failure.

At 24 weeks, the MMR rate was 42% in patients treated with asciminib; this rate increased to 49% by 96 weeks.

The most common (≥20%) adverse events (AEs) with asciminib were upper respiratory tract infections, musculoskeletal pain, fatigue, nausea, rash, and diarrhea. The most common laboratory abnormalities were decreased platelet counts, increased triglycerides, decreased neutrophil counts and hemoglobin, and increased creatine kinase, alanine aminotransferase, lipase, and amylase.

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Tivdak First Antibody–Drug Conjugate FDA Approved for 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 AEs.

The main efficacy measures were confirmed objective response rate and duration of response (DOR). The objective response rate 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%) AEs 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 AEs.

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NEW INDICATIONS

Tecentriq First Immunotherapy Approved for Adjuvant Treatment of Patients with Early-Stage NSCLC and PD-L1 Expression

On October 15, 2021, the FDA approved a new indication for atezolizumab (Tecentriq; Genentech) for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA non–small-cell lung cancer (NSCLC) whose tumors have PD-L1 expression on ≥1% of tumor cells, as determined by an FDA-approved test.

On the same day, the FDA also approved the VENTANA PD-L1 (SP263) Assay (Ventana Medical Systems) as a companion diagnostic test to identify appropriate patients with early-stage NSCLC and PD-L1 expression for adjuvant treatment with atezolizumab.

This new indication is based on results of the IMpower010 trial of patients with stage IB to IIIA NSCLC. Patients in this trial, who had complete removal of their tumors by surgery and received cisplatin-based adjuvant chemotherapy, were randomized to receive atezolizumab injection every 3 weeks for 16 cycles or best supportive care.

The main efficacy end point measure was disease-free survival (DFS) as assessed by the investigator in the primary efficacy analysis population (N = 476) of patients with stage II-IIIA NSCLC with PD-L1 expression on ≥1% of tumor cells. In patients treated with atezolizumab, the median DFS was not reached and was an average of 35.3 months in patients who received best supportive care.

The most common (≥10%) AEs in patients receiving atezolizumab, including laboratory abnormalities, were increased aspartate aminotransferase, blood creatinine, and alanine aminotransferase; as well as hyperkalemia, rash, cough, hypothyroidism, pyrexia, fatigue/asthenia, musculoskeletal pain, peripheral neuropathy, arthralgia, and pruritus.

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FDA Approves Keytruda Regimen for Recurrent or Metastatic Cervical Cancer

On October 13, 2021, the FDA approved a new indication for the PD-1 inhibitor pembrolizumab (Keytruda; Merck) for use in combination with chemotherapy, with or without bevacizumab (Avastin; Genentech), for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors have PD-L1 expression on ≥1% of tumor cells, as determined by an FDA-approved test.

This new indication is based on the phase 3, multicenter, randomized, double-blind KEYNOTE-826 trial of 617 patients with persistent, recurrent, or first-line metastatic cervical cancer who had not received chemotherapy, irrespective of PD-L1 status. Participants were randomized in a 1:1 ratio to receive pembrolizumab 200 mg plus chemotherapy (paclitaxel plus cisplatin or paclitaxel plus carboplatin) with or without bevacizumab, or placebo plus chemotherapy with or without bevacizumab. Pembrolizumab was continued until progressive disease, intolerable toxicity, or 24 months of treatment.

The main efficacy end point measures were overall survival (OS) and progression-free survival. Secondary end point measures included overall response rate (ORR) and DOR.

Pembrolizumab plus chemotherapy with or without bevacizumab demonstrated superior OS (hazard ratio, 0.64; 95% CI, 0.50-0.81; P = .0001) and progression-free survival (hazard ratio, 0.62; 95% CI, 0.50-0.77; P <.0001) compared with placebo plus chemotherapy with or without bevacizumab in patients whose tumors expressed PD-L1 (combined positive score ≥1). In addition, more patients responded to pembrolizumab plus chemotherapy with or without bevacizumab than to placebo plus chemotherapy with or without bevacizumab, with an ORR of 68% (95% CI, 62-74) versus 50% (95% CI, 44-56), respectively. Among patients who responded, the median DOR was 18.0 months for pembrolizumab plus chemotherapy with or without bevacizumab, and 10.4 months for chemotherapy with or without bevacizumab.

The most common (≥20%) AEs were peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, and decreased appetite.

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Verzenio plus Endocrine Therapy Approved for HR-Positive, HER2-Negative, High-Risk Early Breast Cancer

On October 12, 2021, the FDA approved a new indication for the cyclin-dependent kinase 4/6 inhibitor abemaciclib (Verzenio; Eli Lilly), in combination with tamoxifen or an aromatase inhibitor as initial endocrine-based therapy, for the treatment of adult patients with hormone receptor (HR)-positive, HER2-negative, node-positive, early breast cancer at high risk for recurrence, and a Ki-67 score ≥20%, as determined by an FDA-approved test.

This new indication is based on results of the monarchE trial, a randomized, open-label, multicenter study of adult women and men with HR-positive, HER2-negative, node-positive, resected early breast cancer with clinical and pathologic features consistent with a high risk for disease recurrence. Patients were randomized in a 1:1 ratio to receive 2 years of abemaciclib 150 mg twice daily plus physician’s choice of standard endocrine therapy, or standard endocrine therapy alone.

The main efficacy end point measure in the trial was invasive DFS (iDFS). In patients with risk for recurrence and Ki-67 score ≥20%, results showed a statistically significant improvement in iDFS (hazard ratio, 0.62; 95% CI, 0.49-0.8; P = .0042). The iDFS at 36 months was 86.1% (95% CI, 82-88.8) for patients treated with abemaciclib plus endocrine therapy and 79% (95% CI, 75.3-82.3) for those treated with endocrine therapy alone. OS data were not mature at the time of the iDFS analysis.

The most common (≥20%) AEs were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.

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Jakafi a New Treatment Option for Chronic Graft-versus-Host Disease

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.

This new approval was based on the REACH3 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 ORR through cycle 7 of day 1. The ORR was 70% (95% CI, 63%-77%) with ruxolitinib versus 57% (95% CI, 49%-65%) with best available therapy. The median DOR 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 AEs 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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