publication date: Jun. 5, 2020

Drugs & Targets

Atezolizumab + bevacizumab approved by FDA for unresectable HCC

Atezolizumab in combination with bevacizumab was approved by FDA for patients with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy.

Tecentriq and Avastin are sponsored by Genentech, a unit of Roche.

Efficacy was investigated in IMbrave150 (NCT03434379), a multicenter, international, open-label, randomized trial in patients with locally advanced unresectable or metastatic hepatocellular carcinoma who had not received prior systemic therapy. A total of 501 patients were randomized (2:1) to receive either atezolizumab 1200 mg as an intravenous infusion followed by bevacizumab 15 mg/kg IV on the same day, every 3 weeks, or sorafenib orally twice daily.

The main efficacy outcome measures were overall survival (OS) and independent review facility -assessed progression-free survival per RECIST 1.1. Additional efficacy outcome measures were IRF-assessed overall response rate per RECIST 1.1 and mRECIST.

Median OS was not reached in the patients who received atezolizumab plus bevacizumab and was 13.2 months (95% CI: 10.4, NE) in the patients who received sorafenib (HR 0.58; 95% CI: 0.42, 0.79; p=0.0006). Estimated median PFS was 6.8 months (95% CI: 5.8, 8.3) vs. 4.3 months (95% CI: 4.0, 5.6), respectively (HR  0.59; 95% CI: 0.47, 0.76; p<0.0001). The ORR per RECIST 1.1 was 28% (95% CI: 23, 33) in the atezolizumab plus bevacizumab group compared with 12% (95% CI: 7,17) in the sorafenib group (p<0.0001). The ORR per mRECIST was 33% (95% CI: 28, 39) vs. 13% (95% CI: 8, 19), respectively (p<0.0001).

 

Ramucirumab + erlotinib approved by FDA for first-line metastatic NSCLC

Cyramza (Ramucirumab) was approved by FDA in combination with erlotinib for first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) mutations.

Cyramza is sponsored by Eli Lilly and Company.

Efficacy was evaluated in RELAY (NCT02411448), a multinational, randomized, double-blind, placebo-controlled, multicenter study in patients with previously untreated metastatic NSCLC whose tumors have EGFR exon 19 deletion or exon 21 (L858R) substitution mutations. A total of 449 patients were randomized (1:1) to receive either ramucirumab 10 mg/kg or placebo every 2 weeks as an intravenous infusion, in combination with erlotinib 150 mg orally once daily, until disease progression or unacceptable toxicity.

The major efficacy outcome measure was progression-free survival as assessed by the investigator (RECIST 1.1). Additional efficacy outcome measures included overall survival, overall response rate, and duration of response. Median PFS was 19.4 months in the ramucirumab plus erlotinib arm compared with 12.4 months in the placebo plus erlotinib arm (HR 0.59; 95% CI: 0.46, 0.76; p<0.0001).

ORR was 76% in the ramucirumab plus erlotinib arm and 75% in the placebo plus erlotinib arm, with median DoR of 18.0 months and 11.1 months, respectively. At the time of the final analysis of PFS, OS data were not mature as only 26% of the deaths required for the final analysis had occurred (HR 0.83; 95% CI: 0.53, 1.30).

 

Piqray receives positive CHMP opinion to treat HR+/HER2- advanced breast cancer with a PIK3CA mutation

Piqray received a positive opinion from the Committee for Medicinal Products for Human Use of the European Medicines Agency.

CHMP recommended approval of Piqray (alpelisib) in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor positive, human epidermal growth factor receptor-2 negative locally advanced or metastatic breast cancer with a PIK3CA mutation after disease progression following endocrine therapy as monotherapy.

Piqray is sponsored by Novartis.

The CHMP opinion is based on results of the Phase III SOLAR-1 trial that showed Piqray plus fulvestrant nearly doubled median progression-free survival compared to fulvestrant alone in HR+/HER2- advanced breast cancer patients with tumors harboring a PIK3CA mutation (median PFS 11.0 months vs. 5.7 months; HR=0.65, 95% CI: 0.50-0.85; p<0.001), the study’s primary endpoint. PFS subgroup analyses demonstrated consistent efficacy in favor of Piqray, irrespective of presence or absence of lung/liver metastases.

In SOLAR-1, most adverse events were mild to moderate in severity and generally manageable through dose modifications and medical management.

The European Commission will review the CHMP recommendation and usually delivers a final decision within approximately two months. The decision will be applicable to all 27 European Union member states plus the United Kingdom, Iceland, Norway and Liechtenstein. Additional regulatory filings are underway with other health authorities worldwide.

Patients with HR+/HER2- advanced breast cancer should be selected for treatment with Piqray based on the presence of a PIK3CA mutation in tumor or plasma specimens, using a validated test. If a mutation is not detected in a plasma specimen, tumor tissue should be tested if available.

 

Sarclisa approved by European Commission for adults with relapsed and refractory multiple myeloma

Sarclisa (isatuximab) was approved by the European Commission in combination with pomalidomide and dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on the last therapy.

Sarclisa is a monoclonal antibody that binds to a specific epitope on the CD38 receptor of MM cells.

“Sarclisa in combination with pom-dex demonstrated median progression-free survival of nearly one year, a five-month improvement over pom-dex alone, in patients who had already failed at least two prior therapies,” John Reed, global head of research and development at Sanofi, said in a statement.

In the Phase 3 ICARIA-MM study, Sarclisa added to pom-dex (Sarclisa combination therapy, n=154) demonstrated a statistically significant improvement of progression-free survival, with a median PFS of 11.53 months compared to 6.47 months with pom-dex alone (n=153) (HR 0.596, 95% CI: 0.44-0.81, p=0.001). Sarclisa combination therapy also demonstrated a significantly greater overall response rate compared to pom-dex alone (60.4% vs. 35.3%, p<0.0001). In additional analyses, Sarclisa combination therapy compared to pom-dex alone showed a treatment benefit consistent across select subgroups reflective of real-world practice, including patients with high risk cytogenetics, those aged 75 years and older, patients with renal insufficiency and patients who were refractory to lenalidomide.

 

Subcutaneous formulation of Darzalex approved by EC for multiple myeloma

The subcutaneous formulation of Darzalex (daratumumab) was granted marketing approval by the European Commission for the treatment of adult patients with multiple myeloma in all currently approved daratumumab intravenous formulation indications in frontline and relapsed / refractory settings.

Darzalex is sponsored by Genmab. In August 2012, Genmab granted Janssen Biotech Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

The approval follows a Positive Opinion by the CHMP of the European Medicines Agency in April 2020. The SC formulation is administered as a fixed-dose over approximately three to five minutes, significantly less time than IV daratumumab, which is given over several hours.

Patients currently on daratumumab IV will have the choice to switch to the SC formulation.

The approval was based on data from two studies: the phase III non-inferiority COLUMBA (MMY3012) study, which compared the SC formulation of daratumumab to the IV formulation in patients with relapsed or refractory multiple myeloma, and data from the Phase II PLEIADES (MMY2040) study, which is evaluating SC daratumumab in combination with certain standard multiple myeloma regimens.

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