publication date: Mar. 13, 2020
Drugs & Targets
FDA grants accelerated approval to nivolumab and ipilimumab combination for hepatocellular carcinoma
FDA granted accelerated approval to the combination of nivolumab and ipilimumab (Opdivo and Yervoy) for patients with hepatocellular carcinoma who have been previously treated with sorafenib.
Bristol-Myers Squibb Co. sponsors the drugs.
Efficacy of the combination was investigated in Cohort 4 of CHECKMATE-040, (NCT01658878) a multicenter, multiple cohort, open-label trial conducted in patients with HCC who progressed on or were intolerant to sorafenib. A total of 49 patients received nivolumab 1 mg/kg in combination with ipilimumab 3 mg/kg every 3 weeks for four doses, followed by single-agent nivolumab 240 mg every 2 weeks until disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate and duration of response as determined by blinded independent central review using RECIST v1.1. ORR was 33% (n=16; 95% CI: 20, 48), with 4 complete responses and 12 partial responses. Response duration ranged from 4.6 to 30.5+ months, with 31% of responses lasting at least 24 months.
FDA accepts BLA for biosimilar MYL-1402O in cancer indications
FDA has accepted Mylan’s Biologics License Application or MYL-1402O, a proposed biosimilar to Avastin (bevacizumab), for review under the 351(k) pathway.
Mylan and Biocon sponsor MYL-1402O.
The BLA seeks approval of bevacizumab for first-line and second-line treatment of patients with metastatic colorectal cancer in combination with fluorouracil-based chemotherapy; first-line use for patients with non-squamous non-small cell lung cancer; recurrent glioblastoma; metastatic renal cell carcinoma in combination with interferon alfa; and persistent, recurrent or metastatic cervical cancer.
The FDA goal date set under the Biosimilar User Fee Act is Dec. 27, 2020.
Mylan and Biocon’s proposed biosimilar bevacizumab is expected to be the third biosimilar from the partnered portfolio for cancer patients in the U.S. It is currently available in India and other developing markets.
FDA grants Breakthrough Therapy Designation for JNJ-6372 in NSCLC indication
FDA has granted Breakthrough Therapy Designation for JNJ-61186372 (JNJ-6372) for the treatment of patients with metastatic non-small cell lung cancer with epidermal growth factor receptor Exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy.
Janssen Pharmaceutical Companies of Johnson & Johnson sponsors JNJ-61186372.
JNJ-6372 is an EGFR-mesenchymal epithelial transition factor bispecific antibody that targets activating and resistant EGFR and MET mutations and amplifications. Currently, there are no FDA-approved targeted therapies for patients with lung cancer who have EGFR Exon 20 insertion mutations.
Patients with NSCLC and EGFR Exon 20 insertion mutations have a form of disease that is generally insensitive to EGFR tyrosine kinase inhibitor treatments and carries a worse prognosis compared to patients with more common EGFR mutations (Exon 19 deletions/L858R substitution).
The current standard of care for this patient population is conventional cytotoxic chemotherapy.
The Breakthrough Therapy Designation is supported by data from a phase I, first-in-human, open-label, multicenter study (NCT02609776). The study evaluates the safety, pharmacokinetics and preliminary efficacy of JNJ-6372 monotherapy and in combination with lazertinib, a novel third-generation EGFR TKI, in adult patients with advanced NSCLC.
The study seeks to determine the recommended Phase 2 dose in patients with advanced NSCLC. Enrollment into the Part 2 dose expansion cohorts is ongoing, as the study evaluates JNJ-6372 monotherapy activity in multiple NSCLC sub-populations with genomic alterations such as those with C797S resistance mutation or MET amplification.
Thermo Fisher Scientific collaborates with Janssen to co-develop companion diagnostic for cancer
Thermo Fisher Scientific and Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, signed an agreement to co-develop a companion diagnostic in oncology.
The CDx will support clinical trial enrollment globally.
Under the agreement, Thermo Fisher Scientific will collaborate with Janssen Research & Development, LLC scientists to validate multiple biomarkers for use with Thermo Fisher’s Oncomine Dx Target Test, which will be used to identify variant-positive patients for enrollment into clinical trials focused on non-small cell lung cancer. Additional indications in oncology may follow as part of the agreement.
Oncomine Dx Target Test is a next-generation sequencing assay that contains 46 cancer-related biomarkers and a workflow that features a fast turnaround time and the lowest sample requirements on the market for detection of both DNA and RNA variants.
Since its approval by the U.S. Food and Drug Administration in 2017, Oncomine Dx Target Test has been the focus of multiple drug development and clinical trial support agreements between Thermo Fisher and international pharmaceutical companies.
European Commission approves Venclyxto in CLL indication
The European Commission has approved Venclyxto in combination with obinutuzumab for the treatment of adult patients with chronic lymphocytic leukemia, who were previously untreated.
The approval is valid in all 27 member states of the EU, as well as Iceland, Liechtenstein, Norway and the United Kingdom.
AbbVie sponsors the drug.
“This approval underscores the growing utility of Venclyxto in treating CLL and demonstrates its clinical benefit as a chemotherapy-free combination therapy option for CLL patients in Europe who have not yet been treated,” Neil Gallagher, chief medical officer and vice president of development at AbbVie, said in a statement.
This is the third approval for Venclyxto, a first-in-class B-cell lymphoma-2 inhibitor. BCL-2 is a protein that prevents cancer cells from undergoing apoptosis, the process that leads to the natural death or self-destruction of cancer cells. Venclyxto is also approved in combination with rituximab for the treatment of adult patients with CLL who have received at least one prior therapy, and as a monotherapy for the treatment of CLL in the presence or absence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor.
This most recent approval is based on results from the phase III CLL14 clinical trial primary analysis (median follow up of 28 months), which demonstrated superior progression-free survival (PFS; the time on treatment without disease progression or death) as assessed by investigators in patients treated with VENCLYXTO plus obinutuzumab compared to patients who received a standard of care chemotherapy regimen of chlorambucil plus obinutuzumab (hazard ratio 0.35; 95% CI (0.23,0.53), p<0.0001, medians not yet reached).
At an updated CLL14 efficacy analysis (median follow-up of 40 months), the median PFS had not been reached in the Venclyxto + obinutuzumab arm and was 35.6 months [95% CI: 33.7,40.7] in the obinutuzumab + chlorambucil arm (hazard ratio 0.31; 95% CI: 0.22, 0.44). The 36-month PFS estimate in the venetoclax plus obinutuzumab arm was 81.9% [95% CI: 76.5, 87.3] and in the obinutuzumab plus chlorambucil arm was 49.5% [95% CI: 42.4, 56.6]. Additionally, after completing one year of treatment, patients treated with the VENCLYXTO combination experienced deep response as measured by higher rates of undetectable minimal residual disease or complete response as compared to patients receiving a standard of care regimen.