“Array BioPharma’s (NASDAQ: ARRY) wholly-owned MEK inhibitor, binimetinib, and BRAF inhibitor, encorafenib, were showcased at the 2015 annual meeting of the American Society of Clinical Oncology (ASCO). At the meeting, preliminary data for the combination of binimetinib and encorafenib from a Phase 1b/2 dose escalation and expansion study in patients with BRAF-mutant melanoma who are BRAF inhibitor treatment naive were shared during an oral presentation. Results from the study indicate that binimetinib and encorafenib may be safely combined and show encouraging clinical activity consistent with MEK/BRAF inhibitor expectations in patients with BRAF-mutant melanoma who are BRAF inhibitor treatment naive. In addition, a differentiated safety profile relative to other MEK/BRAF inhibitor combinations is emerging in the dose range currently being used in the Phase 3 COLUMBUS trial. Array expects updated BRAF melanoma data from the ongoing Phase 2 combination trial (LOGIC-2) of binimetinib and encorafenib followed by the addition of a third targeted agent identified based on genetic testing at the time of progression will be submitted to a scientific conference later this year. LOGIC-2 utilizes the same dose of binimetinib and encorafenib currently being studied in the COLUMBUS trial.”
“Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced follow-up data from two studies of the investigational MEK inhibitor cobimetinib in combination with Zelboraf® (vemurafenib). Updated data from the pivotal coBRIM Phase III study showed the combination helped people with previously untreated BRAF V600 mutation-positive advanced melanoma live a median of one year (12.3 months) without their disease worsening or death (progression-free survival; PFS) compared to 7.2 months with Zelboraf alone (hazard ratio [HR]=0.58, 95 percent confidence interval [CI] 0.46-0.72).1
“ ‘The combination of cobimetinib and Zelboraf extended the time people lived without their disease getting worse to a year,’ said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. ‘These results are exciting because they underscore the importance of combining medicines that target the signals, which cause about half of all melanomas to grow.’ “
It has become routine practice to prescribe targeted drugs to patients with metastatic non-small cell lung cancer (NSCLC), whose tumors harbor molecular alterations in EGFR, ALK, and ROS. However, the majority of patients with NSCLC have no targetable mutations and lack good treatment options. Enter immunotherapy drugs, specifically ‘immune checkpoint blockade antibodies,’ to which many refer simply as ‘anti-PD-1 drugs,’ or simply ‘PD-1 drugs.’ In this post, I provide some updates on the efficacy of anti-PD-1 and anti-PD-L1 drugs in lung cancer. Continue reading…
“A closely watched immune system-boosting drug cocktail from Britain’s AstraZeneca shows promise in advanced lung cancer, despite adverse side effects in a number of patients.
“Researchers said on Wednesday that the combination of the experimental drugs MEDI4736 and tremelimumab had ‘a manageable safety profile with evidence of clinical activity, including in PD-L1 negative disease’.
“The update was provided in a scientific summary, or abstract, released ahead of the annual meeting of the American Society of Clinical Oncology (ASCO) later this month.
“MEDI4736 is an anti-PD-L1 therapy, which works by stopping a tumor’s ability to evade the body’s defenses. Tremelimumab blocks a different molecule, CTLA-4, that also keeps the immune system from attacking cancer.”
“After identifying three different types of resistance to a promising investigational lung cancer drug in a phase 1 trial, a team of researchers led by Dana-Farber Cancer Institute scientists say new targeted inhibitors and combinations are urgently needed to stay ahead of tumors’ constant and varied molecular shape-shifting.
“The researchers, including scientists from pharmaceutical company AstraZeneca, report in an advanced online publication in Nature Medicine on May 4, that their findings indicate ‘an underappreciated genomic heterogeneity’ in mechanisms of resistance to tyrosine kinase inhibitor (TKI) drugs that target the Epidermal Growth Factor Receptor (EGFR) mutation that drive some cases of non-small cell lung cancer (NSCLC).
” ‘If resistance that is this complex is constantly evolving before us, it may mean we need multiple targeted therapies in combination to stay ahead of the resistant cancer,’ said Geoffrey Oxnard, MD, a thoracic oncologist and lung cancer researcher at Dana-Farber and senior author of the report.”
The drugs pembrolizumab (Keytruda) and nivolumab (Opdivo) were approved by the U.S. Food and Drug Administration (FDA) in 2014 and 2015, respectively. These two competing blockbuster drugs are already changing the outlook in metastatic melanoma, previously considered to be a fatal disease. Known as ‘immune checkpoint inhibitors,’ they work by releasing ‘brakes’ on a patient’s own immune system, freeing it to attack tumors. In the wake of their success, researchers are now taking immune checkpoint inhibition in new directions. Continue reading…
“Chemotherapy can be very effective against small prostate tumors. Larger prostate tumors, however, accumulate cells that suppress the body’s immune response, allowing the cancer to grow despite treatment. Researchers at the University of California, San Diego School of Medicine now find that blocking or removing these immune-suppressing cells allows a special type of chemotherapy—and the immune cells it activates—to destroy prostate tumors. This novel combination therapy, termed chemoimmunotherapy, achieved near complete remission in mouse models of advanced prostate cancer.
“The study is published April 29 in Nature.
“Advanced or metastatic prostate cancer does not typically respond to chemotherapy. Prostate cancers also fail to respond to a promising new type of immunotherapy drugs, called checkpoint inhibitors, which disable cancer cells’ cloaking mechanism so that a person’s own immune system can better fight the tumor. This specific resistance is likely due in part to immunosuppressive B cells, which are more common in larger prostate tumors in mice, as well as in advanced and metastatic prostate cancer in humans. As the name suggests, these cells keep the immune system at bay, rendering most therapies ineffective and allowing malignant tumors to grow unchecked.”
Editor’s note: Please note that this research was performed in mice, not in people.