Roche: "MPDL3280A Doubled the Likelihood of Survival Compared with Chemotherapy in People with a Specific Type of Lung Cancer"

“Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced interim results from a global, randomised Phase II study (POPLAR) in people with previously treated NSCLC. The study showed the investigational cancer immunotherapy MPDL3280A (anti-PDL1) doubled the likelihood of survival (overall survival [OS]; HR=0.47) in people whose cancer expressed the highest levels of PD-L1 (programmed death ligand-1) compared with docetaxel chemotherapy. An improvement in survival was also observed in people who had medium and high (HR=0.56) or any level of PD-L1 expression (HR=0.63), as characterised by a test being developed by Roche. MPDL3280A was generally well tolerated and adverse events were consistent with what has been previously reported for MPDL3280A in NSCLC. Updated results will be presented in an oral session at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO).

“ ‘In our study of MPDL3280A in previously treated lung cancer, the amount of PD-L1 expressed by a person’s cancer correlated with improvement in survival,’ said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. ‘The goal of PD-L1 as a biomarker is to identify people most likely to experience improved overall survival with MPDL3280A alone and which people may be appropriate candidates for a combination of medicines.’ “

UPDATE 2-Bristol's Opdivo Proves Effective Against Second Type of Lung Cancer

“A large study of Bristol-Myers Squibb Co’s Opdivo treatment has been halted after proving the drug is effective against the most common form of lung cancer, the company said, positioning the medicine for far wider use than its already approved lung cancer and melanoma indications.

“The U.S. drugmaker on Friday said the study, called Checkmate-057, was stopped early after an independent data monitoring committee concluded that Opdivo provided a survival advantage over docetaxel, a standard chemotherapy, among patients with previously treated non-squamous non-small cell lung cancer (NSCLC).

“The so-called PD-1 inhibitor, which works by taking the brakes off the immune system, was approved by U.S. regulators last month to treat the less-common “squamous” form of NSCLC that had spread following treatment with chemotherapy.

“Opdivo is also approved for use against metastatic melanoma following treatment with Yervoy, another Bristol-Myers immuno-therapy.”

New drug ONT-380 Shows Early Promise Against HER2-Positive, Metastatic Breast Cancer

The gist: A new targeted drug for HER2-positive, metastatic breast cancer has shown some early promise in clinical trials, and testing will continue to see whether it might be a good treatment option for patients. The drug is called ONT-380 (aka ARRY-380). In one trial, it is being tested in combination with the drug Kadcyla. In another trial, it is being combined with Xeloda (aka capecitabine) and/or Herceptin (aka trastuzumab). Both trials are testing ONT-380 in patients who have already tried other treatments.

“Oncothyreon Inc. (ONTY) today announced that positive preliminary data from two ongoing Phase 1b trials of ONT-380 (ARRY-380), an orally active, reversible and selective small molecule HER2 inhibitor, will be presented at the San Antonio Breast Cancer Symposium…

“ONT-380 was well-tolerated in both studies and in all combinations tested. The most common adverse events included nausea and vomiting, diarrhea, fatigue and elevated liver function tests. Most adverse events were grade 1 or 2 in severity. Elevated liver function tests were more common in patients also receiving Kadcyla. No grade 3 diarrhea was seen in either trial; anti-diarrheal prophylaxis was not a study requirement…

” ‘The preliminary signs of efficacy in both of these trials are encouraging for the further development of ONT-380,” said Stacy Moulder, M.D., Associate Professor, Breast Medical Oncology, University of Texas MD Anderson Cancer Center. “These patients were heavily pre-treated, with the majority already having a history of CNS metastases. Nevertheless, meaningful responses and prolonged stable disease have been observed and many patients currently remain on study. Importantly, ONT-380 has been well-tolerated, with a toxicity profile that facilitates its combination with other agents.”

” ‘We are continuing to enroll patients in both of these Phase 1b trials,’ said Diana Hausman, M.D., Chief Medical Officer of Oncothyreon. ‘We are currently testing an increased dose level of ONT-380 of 350 mg twice daily in both trials. We are also enrolling cohorts of patients in both trials with CNS metastases from HER2+ breast cancer that are either asymptomatic and untreated or progressive following treatment to better define the potential role of ONT-380 in treating patients with this serious unmet medical need.’ ”


New Drug Shows Promise for Metastatic Triple-Negative Breast Cancer Patients Who Have Already Taken Previous Treatments

The gist: A drug called sacituzumab govitecan has shown promising results in a clinical trial in patients with metastatic triple-negative breast cancer (TNBC) who have taken previous treatments. In the trial, patients generally experienced a longer period of time without their cancer worsening when they took sacituzumab govitecan compared to when they took their last treatment for TNBC.

Immunomedics, Inc. , (Nasdaq:IMMU) today announced that sacituzumab govitecan, the Company’s novel investigational antibody-drug conjugate (ADC), continues to produce a partial response (PR) rate of 30% and a 70% clinical benefit rate (CBR), defined as PR and stable disease, in patients with metastatic triple-negative breast cancer (TNBC) who had been heavily pretreated. For patients with PR or stable disease longer than 6 months, the CBR was 40%. Significantly, PRs ranging from 30% to 70% tumor shrinkage as best response were reported. Responses are measured by computed tomography (CT) based on RECIST 1.1 criteria.

“Dr. Aditya Bardia of Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, presented the Phase 1/2 study at the San Antonio Breast Cancer Symposium in San Antonio, TX. Commenting on the results, Dr. Bardia stated, ‘TNBC patients in this late-stage setting have limited treatment options that are effective. We are quite encouraged with this experience with sacituzumab govitecan, especially the time-to-progression results, which showed that the duration of response for the responding patients was generally longer than their last prior therapy for TNBC.’ ”

“As the name implies, TNBC represents breast cancers that are negative for estrogen and progesterone receptors, as well as human epidermal growth factor receptor 2, or HER2. This type of breast cancer comprises about 15-20% of all invasive breast cancers and is more prevalent in young and African-American women. Despite the fact that initial responses with chemotherapy are high, TNBC characteristically has a high recurrence rate and is perhaps the most difficult type of breast cancer to treat successfully with current cytotoxic agents. According to a published report, the median survival for patients with metastatic triple-negative breast cancer is estimated to be 13 months. 1 Currently, there are no targeted treatments available for TNBC.”

New Treatment Combo Shows Good Preliminary Results in Clinical Trial for Metastatic, HER2+ Breast Cancer

The gist: A drug called neratinib (aka PB272) is showing positive results so far in a clinical trial in patients with HER2-positive metastatic breast cancer. The drug is being given in combination with the drug temsirolimus. The patients in the trial have taken a median of three previous treatments for their breast cancer.

“Puma Biotechnology, Inc. (PBYI), a development stage biopharmaceutical company, announced that interim results from an ongoing Phase II clinical trial of Puma’s investigational drug PB272 (neratinib) were presented at the 2014 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas. The trial was supported by the National Comprehensive Cancer Network®, ASCO’s Young Investigator Award, Susan G. Komen for the Cure®, and the Terri Brodeur Breast Cancer Foundation. The presentation is further detailed below.

“The trial was conducted as a Phase I/II trial of PB272 given in combination with the anticancer drug temsirolimus in patients with HER2-positive metastatic breast cancer…

“The interim efficacy results from the trial showed that for the 37 patients in the MTD cohort, 11 patients (30%) experienced a partial response (PR). The median duration of response for this cohort of patients was 3.0 months and the median progression free survival was 4.8 months. For the 37 evaluable patients in the DE cohort, the efficacy results from the trial demonstrated that 11 patients (30%) experienced a partial response (PR). The median duration of response for this cohort of patients was 7.4 months and the median progression free survival is not yet mature. There are a total of 18 patients currently on active treatment in the trial. 8 of the 17 active patients in the DE cohort have not yet had tumor assessments.

“Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, ‘We continue to be pleased with the data on the combination of PB272 with temsirolimus. This interim data continues to demonstrate strong antitumor activity in a heavily pretreated population and compares favorably to what would typically be seen for other treatment options for patients in this setting. We look forward to following the remaining patients on study to completion of the trial and advancing the combination of PB272 and temsirolimus into Phase III trials in 2015.’ “

Ipilimumab in Advanced Melanoma: Added Benefit for Non-Pretreated Patients Not Proven

“The German Institute for Quality and Efficiency in Health Care (IQWiG) already assessed the added benefit of ipilimumab in advanced melanoma in 2012. A considerable added benefit was found for patients who had already received previous treatment. In the new dossier compiled by the drug manufacturer, the drug was now compared with the appropriate comparator therapy dacarbazine specified by the Federal Joint Committee (G-BA) also for non-pretreated patients.”

Editor’s Note: This story is a little confusing, so here is a summary to clarify: It was already known that ipilimumab can be beneficial for people who have received previous treatment for melanoma. A new study aimed to find out if ipilimumab also improves survival for patients who have not received prior treatment. However, for a variety of reasons, the study did not show that ipilimumab performs any better than dacarbazine in patients who have not received prior treatment.