Lung-MAP Precision Medicine Trial Makes Exciting Changes

“The team behind the Lung Cancer Master Protocol (Lung-MAP), a groundbreaking clinical trial for patients with advanced squamous cell lung cancer, is announcing exciting new changes and enrolling more patients as it adapts to the latest science and treatments. The nation-wide precision medicine trial now includes nivolumab, the immunotherapy treatment recently approved by the U.S. Food and Drug Administration

“Lung-MAP tests several new treatments for patients with advanced stage squamous cell . In advanced stage squamous patients, cancer has usually spread from the lungs to other organs. The trial is for these patients, whose cancer has continued to grow – even after being treated with standard therapy.

“Lung-MAP gives these patients access to innovative therapies. The trial design allows several drugs to be tested simultaneously. Currently, the trial has four trial options for patients. Here’s how it works. All qualifying patients enrolled in Lung-MAP get free genomic profiling. Based on results of that DNA tumor tissue test, patients can be assigned to one of three biomarker-driven sub-studies, each evaluating a promising new drug. If there is no genomic match, patients can enroll in a fourth sub-study, which is testing the FDA-approved nivolumab, an immunotherapy made by Bristol Myers Squibb, against a nivolumab combination therapy. Regardless of their genomic profile, all Lung-MAP patients receive a treatment – not a placebo.”


Nivolumab and Ipilimumab Combination Active as First-Line Therapy for Advanced NSCLC

“Nivolumab (Opdivo) and ipilimumab (Yervoy), a chemotherapy-free regimen, showed activity as a first-line therapy for patients who have advanced non-small cell lung cancer (NSCLC), according to a preliminary clinical trial that was presented at this year’s World Conference on Lung Cancer.

“Four different regimens of nivolumab, the PD-1 inhibitor, and ipilimumab, the anti-CTLA-4 antibody, led to response rates of 13% to 39% in 148 patients with no prior exposure to systemic therapy. The combination produced deep and durable responses, with a low rate of treatment-emergent grade 3/4 adverse events (AEs) leading to discontinuation.

“ ‘Clinical activity was observed regardless of tumor PD-L1 expression,’ said lead investigator Naiyer A. Rizvi, MD, director of Thoracic Oncology and Immunotherapeutics at Columbia University Medical Center. ‘We have preliminary evidence of greater activity in tumors that have 1% or greater PD-L1 expression. The median disease control rate [response plus stable disease] was not reached in any arm, regardless of PD-L1 expression.’ “


BIND-014 Being Tested as Treatment for Advanced/Metastatic NSCLC That's Squamous or KRAS+

The gist: The first patient has been enrolled in a clinical trial testing the drug BIND-014 in patients with advanced or metastatic non-small cell lung cancer (NSCLC) that is squamous or has a mutation in the KRAS gene. An earlier clinical trial found promising results for these patients. BIND-014 is a new form of the chemotherapy drug docetaxel. It is meant to home in on cancer cells to deliver chemotherapy directly.

“BIND Therapeutics, Inc. (BIND), a clinical-stage nanomedicine platform company developing targeted and programmable therapeutics called Accurins™, today announced its 2015 strategic overview and enrollment of the first patient expressing a KRAS mutation in a global, multicenter two-tiered phase 2 trial with BIND-014 in non-small cell lung cancer (NSCLC) patients with KRAS mutant tumors (mutated Kirsten ras oncogene homolog) or squamous histology. The trial was driven by positive results from the phase 2 trial in NSCLC presented at the EORTC-NCI-AACR Annual Symposium in Barcelona on November 19, 2014, with a confirmed objective response rate of 22 percent (n=9); one KRAS mutant NSCLC PR was also seen in the phase 1 trial with BIND-014, yielding a combined total response rate of 30 percent (n=10). Results from the phase 2 trial also suggested meaningful differentiation in NSCLC patients with squamous histology when compared to historical docetaxel results. BIND-014 results presented at EORTC-NCI-AACR also demonstrated a disease control rate of 66 percent and overall survival of 11.1 months (n=9) in NSCLC patients with squamous histology. BIND intends to begin accruing NSCLC patients with squamous cell histology in the two-tier phase 2 trial in 1Q 2015.”


Prostate Cancer Drug Xtandi Shows Promise for Treating Advanced, AR+ Triple-Negative Breast Cancer

The gist: A prostate cancer drug called Xtandi (aka enzalutamide) might also help treat women with advanced, androgen receptor-positive triple-negative breast cancer (TNBC). More research will need to be done to see whether Xtandi outperforms standard chemotherapy for these patients.

“Preliminary results from a Phase II trial of Astellas’ Xtandi (enzalutamide) show positive benefits for the prostate cancer drug when used as a single therapy to treat women with advanced androgen-receptor positive, triple-negative breast cancer.

“But Novartis’ bid to prove benefits for Afinitor (everolimus) as a first-line treatment for women with HER2-positive advanced breast cancer failed, after a Phase III trial found no benefit in this group of patients. [See more here.]

“The data from both studies were presented at the San Antonio Breast Cancer Symposium in Texas. The trial involving Xtandi is the largest to date in patients with androgen-receptor positive triple-negative breast cancer, and the first to report objective responses to a hormonal therapy.

“The study found that out of 26 women evaluated, 11 showed a clinically significant benefit after 16 weeks and 9 showed benefit after 24 weeks. More data is due in 2015 from a further 76 women enrolled in the study, but so far researchers have observed positive responses in one woman and partial positive responses in three more women in this group.”


Boehringer's Vargatef Approved in the EU for Lung Cancer

The gist: Lung cancer patients in the EU will now be able to take the drug Vargatef (aka nintedanib) in combination with the chemotherapy drug docetaxel. The treatment has been approved by the European Commission for adults with locally advanced, metastatic, or locally recurrent non-small cell lung cancer (NSCLC).

“The European Commission granted marketing authorisation for Vargatef (nintedanib) in combination with docetaxal for use in adult patients with locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC) after first-line chemotherapy.

“Prof Klaus Dugi, Boehringer’s chief medical officer, said: ‘The approval of Vargatef expands our oncology portfolio, following last year’s approval of Giotrif (afatinib) for another specific type of lung cancer.’

“The launch of Giotrif/Gilotrif in 2013 as a treatment lung cancer patients who express epidermal growth factor receptor (EGFR) marked Boehringer’s entry onto the oncology market.

“The addition of Vargatef widens the potential patient base for the German company, allowing Boehringer to make sizeable inroads into lung cancer.”


Lanreotide Improves Survival with Enteropancreatic Tumors

The gist: A clinical trial with volunteer patients tested the effectiveness of a drug called lanreotide for people with grade 1 or 2 metastatic enteropancreatic neuroendocrine tumors. The researchers found that, compared to taking a “fake” placebo drug, lanreotide increased the amount of time patients lived without their disease worsening. However, lanreotide did not improve overall survival or quality of life.

“Lanreotide significantly improves survival among patients with metastatic enteropancreatic neuroendocrine tumors (grade 1 or 2), according to a study published in the July 17 issue of the New England Journal of Medicine.

“Martyn E. Caplin, D.M., from Royal Free Hospital in London, and colleagues conducted a multinational study of patients with advanced, well-differentiated or moderately-differentiated, nonfunctioning, somatostatin receptor-positive neuroendocrine tumors (grade 1 or 2 that originated in the pancreas, midgut, or hindgut, or were of unknown origin) and documented disease-progression status. Participants were randomly assigned to receive an extended-release aqueous-gel formulation of lanreotide at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks.

“The researchers found that, compared to placebo, lanreotide was associated with significantly prolonged progression-free survival (P placebo group. In predefined subgroups, the therapeutic effect was generally consistent with that found in the overall population. Groups were similar in quality of life and overall survival. Diarrhea was the most common treatment-related adverse event (26 percent of the lanreotide group versus 9 percent of the placebo group).”


Phase III Trial Shows Improved Survival with TAS-102 in Metastatic Colorectal Cancer Refractory to Standard Therapies

“The new combination agent TAS-102 is able to improve overall survival compared to placebo in patients whose metastatic colorectal cancer is refractory to standard therapies, researchers said.

” ‘Around 50% of patients with colorectal cancer develop metastases but eventually many of them do not respond to standard therapies,’ said Takayuki Yoshino of the National Cancer Centre Hospital East in Chiba, Japan, lead author of the phase III RECOURSE trial. ‘The RECOURSE study shows that TAS-102 improves overall survival in these patients compared to placebo. I believe that this agent will become one of the standards of care in the refractory setting of metastatic colorectal cancer in Japan and worldwide.’

“TAS-102 is a novel nucleoside anti-tumour agent consisting of trifluridine (FTD) and tipiracil hydrochloride (TPI). FTD is the active component of TAS-102 and is directly incorporated into cancer DNA, leading to DNA dysfunction. However, when FTD is taken orally it is largely degraded to an inactive form. TPI prevents the degradation of FTD. This mechanism of action is different to that of fluoropyrimidine, oxaliplatin and irinotecan…

“Douillard concluded: ‘In RECOURSE, TAS-102 was tested in patients who had received all types of chemotherapy available for colorectal cancer. I would probably move this drug into an earlier line of treatment and I would also combine it with either irinotecan or oxaliplatin.’ ”

Editor’s note: This story discusses the results of a clinical trial that tested a new treatment for colorectal cancer in volunteer patients. The trial tested whether the treatment—called TAS-102—benefits people with metastatic cancer that has not responded to standard treatment. Some patients in the trial were treated with TAS-102, and for comparison, some were given a “fake” placebo treatment. The results showed that patients treated with TAS-102 survived longer than patients who took the placebo.


PD-1 Antibody Demonstrated Encouraging Activity in Metastatic Melanoma

“Heavily pretreated patients with metastatic melanoma who received the humanized anti-PD-1 monoclonal antibody pidilizumab demonstrated encouraging rates of 12-month OS, according to results of a phase 2 study presented at the ASCO Annual Meeting.

“ ‘Activity was previously seen [with pidilizumab] in two lymphoma populations in phase 2 studies,’ researcher Michael B. Atkins, MD, deputy director of Georgetown-Lombardi Comprehensive Cancer Center in Washington, and professor of oncology and medicine at Georgetown University School of Medicine, said during a presentation. ‘Correlative studies in those lymphoma populations supported a PD-1/PD-L1–linked mechanism of action, and importantly there was no change or an increase in PD-1–positive CD4 and CD8 lymphocytes and CD14 monocytes following the drug, excludingantibody-dependent cellular cytotoxicity of PD-1–positive cells as a consequence of therapy.’ “

Editor’s note: Pidilizumab is a new drug that that might benefit people with metastatic melanoma who have already been heavily treated. A recent clinical trial testing it in volunteer patients found some promising results, but further studies will be needed to see how to use pidilizumab most effectively, in terms of dosage and combining it with other drugs. Pidilizumab is an “anti-PD-1” immunotherapy, meaning that it interacts with a protein called PD-1 to boost a patient’s own immune system to fight cancer. Learn more about immunotherapy treatments for melanoma at our Need to Know blog.


Basilea Announces Start of Phase 2a Study with Oncology Drug Candidate BAL101553

“Basilea Pharmaceutica Ltd. (SIX: BSLN) reports today that it initiated a phase 2a study with its investigational oncology drug BAL101553. The study is designed to further characterize safety and tolerability, and to obtain efficacy data in adult patients with advanced or recurrent solid tumors who have failed standard therapy or for whom no effective standard therapy is available. Tumor types were selected based on clinical observations in the phase 1 study and a detailed analysis of potential patient stratification biomarkers across tumor indications. The study will also continue the extensive biomarker testing initiated in Phase 1, to further evaluate dose and patient populations most likely to respond.”

Editor’s note: A drug company is starting a clinical trial to test a new cancer drug called BAL101553 in volunteer patients. The trial is enrolling people with advanced or recurrent solid tumors, including people with colorectal cancer, gastric cancer or cancers of the gastro-esophageal junction, non-small cell lung cancer (NSCLC), ovarian cancer (or primary peritoneal), pancreatic cancer (including ampullary), and triple-negative breast cancer. Specifically, the trial is open to patients who have tried a standard treatment without benefitting or who, for whatever reason, have no effective standard treatment available to them. BAL101553 has already shown promise for some patients in a phase I trial. The new trial will continue to examine the safety and effectiveness of the drug, and it will also test patients’ tumors for specific biomarker molecules to see if patients with certain biomarkers are more likely to benefit.