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NEWS AND PUBLICATIONS

Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC

While platinum-based chemotherapy is a mainstay in the treatment of non-small cell lung cancer (NSCLC), monoclonal antibody therapies such as the anti-programmed cell death ligand 1 (anti-PD-L1) represent attractive alternatives. The pivotal open-label IMpower110 Phase 3 trial evaluated the efficacy of atezolizumab in patients with metastatic (non)squamous NSCLC. In a subgroup of 205 patients who had the highest PD-L1 expression, the median overall survival (OS) was longer by 7.1 months in the atezolizumab vs the chemotherapy groups (20.2 months vs. 13.1 months; hazard ratio for death, 0.59; P=0.01). Among safety-evaluable patients, adverse events (AEs) occurred in 90.2% vs 94.7% of atezolizumab- vs chemotherapy-treated patients; Grade 3 or 4 AEs occurred in 30.1% and 52.5% of patients. OS and progression-free survival favored atezolizumab in the subgroups with a high blood-based tumor mutational burden. Altogether, these results, published in the New England Journal of Medicine, show the benefit of atezolizumab over chemotherapy in patients with metastatic NSCLC.

INDUSTRY

EMA

The Committee for Medical Products for Human Use (CHMP) adopted a positive opinion for:

New medicines:

New generic medicines:

  • Lenalidomide (Lenalidomide Mylan, Mylan Ireland Limited), a generic of Revlimid, for the treatment of multiple myeloma and follicular lymphoma.

Extensions of indications:

  • Blinatumomab (Blincyto, Amgen Europe) as monotherapy for the treatment of adult patients with CD19-positive relapsed/refractory B-precursor Acute lymphoblastic leukemia (ALL). Patients with Philadelphia chromosome positive B-precursor ALL should have failed treatment with at least 2 tyrosine kinase inhibitors (TKIs) and have no alternative treatment options.
  • Nivolumab (Opdivo, Bristol-Myers Squibb Pharma EEIG) as monotherapy for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum-based combination chemotherapy.

FDA

The FDA granted approval for:

  • Cobas EGFR mutation test v2 (Roche), as a companion diagnostic for the detection of endothelial growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) for both tissue and plasma samples, with results available in less than eight hours.
  • FoundationOne CDx test (Foundation Medicine), a next-generation sequencing-based test as a companion diagnostic to identify fusions in the neurotrophic receptor tyrosine kinase (NTRK) genes NTRK1, NTRK2, and NTRK3, in DNA isolated from tumor tissue specimens from patients with solid tumors eligible for treatment with larotrectinib (VITRAKVI, Bayer Healthcare Pharmaceuticals). Larotrectinib was granted accelerated approval on November 26, 2018, for adult and pediatric patients with solid tumors that have a NTRK gene fusion without a known acquired resistance mutation, that are either metastatic or where surgical resection is likely to result in severe morbidity, and who have no satisfactory alternative treatments or whose cancer has progressed following treatment.
  • Venetoclax (Venclexta, Abbvie and Genentech), in combination with azacytidine, decitabine, or low-dose cytarabine (LDAC) for newly-diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities precluding intensive induction chemotherapy. Approval is based on the Phase III VIALE-A trial, which reported an improvement in median overall survival (OS) from 9.6 to 14.7 months in patients treated with placebo plus azacytidine vs venetoclax plus azacytidine, and on the Phase III VIALE-C trial, which reported a complete response rate of 27% vs 7.4% in patients treated with venetoclax plus LDAC vs placebo plus LDAC. 
  • Pembrolizumab (Keytruda, Merck), as expanded label, as monotherapy for adult patients with relapsed/refractory classical Hodgkin’s lymphoma. Approval is based on the Phase III KEYNOTE-204 trial, which reported a reduction in the risk of disease progression or death by 35% after pembrolizumab vs brentuximab vedotin treatment. Median progression-free survival (PFS) treatment was 13.2 vs 8.3 months.
  • Nivolumab and ipilimumab (Opdivo and Yervoy, Bristol-Myers Squibb) as first-line treatment for adult patients with unresectable malignant pleural mesothelioma. Approval was based on the pivotal Phase III CHECKMATE-743 trial, which reported median OS and progression-free survival (PFS) of 18.1 vs 14.1 months and 6.8 vs 7.2 months, respectively, in patients treated with the combination vs standard chemotherapy. Median response duration was 11.0 vs 6.7 months in the combination vs the chemotherapy arms.

The FDA also granted breakthrough therapy designation to the following drugs/devices to advance their development:

  • IMGN632, a leading CD123-targeting antibody-drug conjugate currently in clinical development for treatment of relapsed/refractory blastic plasmacytoid dendritic cell neoplasm. 

Guidelines

On 01Oct2020, the FDA issued two draft guidances to help facilitate the development of adjuvant treatment for renal cell carcinoma and bladder cancer. In these guidances, the FDA addresses approaches to decrease the variability in the design, conduct, and analysis of clinical trial for adjuvant treatment of kidney and bladder cancers. The guidances provide unified recommendations for a consistent approach to trial eligibility criteria, imaging disease assessments, determination of disease recurrence, and trial analysis that will hopefully improve interpretation of trial results for patients enrolled in these clinical trials.

On 08Oct2020, the FDA issued a draft guidance to encourage the inclusion of premenopausal women in breast cancer clinical trials that investigate the efficacy of hormonal drug and biological products. Historically, premenopausal women have been excluded from clinical trials that investigated the efficacy of hormonal drugs for the treatment of hormone positive breast cancer, largely due to concerns about potential differences in how these hormonal drug and biological products would behave in these women. This exclusion resulted in delays in availability of these therapies for premenopausal women. The FDA is of the opinion that, with sufficient estrogen suppression, hormonal drug and biological products are likely to have similar efficacy and safety in premenopausal as in postmenopausal women.

The Clinical Trials Facilitation and Coordination Group (CTFG), Heads of Medicines Agencies (HMA) published an updated guidance regarding recommendations related to contraception and pregnancy testing in clinical trials, with the following changes incorporated:

  • After the relevant systemic exposure to the medicinal product has ended for exposure to other types of genotoxicants than aneugenic compounds, the duration for applying highly effective contraception measures for women of childbearing potential, has been extended from 1 month to 6 months (one folliculogenesis cycle).
  • The need for informing participants to seek advice about donation and cryopreservation of germ cells in line with this guidance prior treatment if applicable, has been added to the section on the need for sexual counseling of study subjects, e.g. in adolescents, which should be reflected in the protocol.

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