PharmaMar Announces New Advances in Oncology at ASCO 2015 for Its Compounds YONDELIS® and PM1183 in Small Cell Lung Cancer, Soft Tissue Sarcoma, and Mesothelioma

“PharmaMar announces that it will present several clinical studies to showcase the data obtained in various tumor types, including SCLC, soft tissue sarcoma and mesothelioma during the 51st American Society of Clinical Oncology meeting in Chicago (ASCO; May 29-June 2). Abstracts have been selected for oral presentation, poster discussion session and general poster presentation. The studies presented by the Company will include the first-in-class drug YONDELIS® (trabectedin), and the second-generation of this class, PM1183 (lurbinectedin). PM1183 is an inhibitor of the transcriptional machinery and a DNA repair complex, which have proven to be crucial in different tumor types, including SCLC, soft tissue sarcoma and ovarian cancer. In addition, these drugs have been shown to have an effect on the tumor microenvironment by targeting tumor-associated macrophages, which is relevant for cancers such as mesothelioma and ovarian cancer, in which chronic inflammation seems to be a hallmark of the disease.”


Benefits of Surgical Resection for Small Cell Lung Cancer Remain Unclear

“Although surgical resection resulted in reasonable outcomes among well-chosen patients with early-stage small cell lung cancer, use of the treatment approach in this setting remains controversial, according to study results.

“Intrathoracic recurrence — the most common treatment failure in the study — occurred more frequently in patients who underwent limited resections. Thus, the researchers determined additional research is needed to assess the overall efficacy of combining surgery with chemotherapy and radiation therapy.

“ ‘Small cell lung cancer (SCLC) accounts for approximately 15% of the primary lung cancer diagnoses in the United States each year,’ Yolanda I. Garces, MD, of the department of radiation oncology at the Mayo Clinic in Rochester, Minnesota, and colleagues wrote. ‘The current National Comprehensive Cancer Network guidelines recommend surgical resection as the preferred first-line treatment for patients with early-stage, node-negative disease. The purpose of this study was to evaluate clinical outcomes and patterns of recurrence in a single-institution series of patients undergoing curative resection of SCLC.’ ”


Maintenance Sunitinib Improved PFS in Extensive-Stage SCLC

“The use of maintenance sunitinib improved progression-free survival (PFS) over placebo among patients with untreated extensive-stage small-cell lung cancer (SCLC) in a new phase II study.

“ ‘Most of the 30,000 patients newly diagnosed each year with SCLC in the United States have extensive-stage disease,’ wrote study authors led by Neal E. Ready, MD, PhD, of Duke University Medical Center in Durham, North Carolina. ‘Despite achieving good disease control initially, patients with SCLC usually experience relapse within 6 months of first-line chemotherapy and often do not respond to subsequent chemotherapy.’

“In previous studies, maintenance chemotherapy after standard platinum-based therapy did not show any overall survival benefit. The new study aimed to test whether sunitinib, a small-molecule tyrosine kinase inhibitor that inhibits VEGF receptors and other targets. Results of the new study were published online ahead of print in the Journal of Clinical Oncology.

“The study enrolled a total of 144 patients, 49 of whom progressed or did not complete induction chemotherapy; 95 patients were randomly assigned to a placebo maintenance therapy group (46 patients) or a sunitinib maintenance therapy group (49 patients), and five patients on each arm did not receive the maintenance therapy. Sunitinib patients received 37.5 mg per day until progression.”


A New Drug Shows Promise in Small Cell and Non-Small Cell Lung Cancer

“Immunomedics, Inc., (Nasdaq:IMMU) today announced that 33% of patients with small cell lung cancer (SCLC) and 31% with non-small cell lung cancer (NSCLC) had their tumor reduced in size by 30% or more, after being treated with sacituzumab govitecan, the Company’s lead investigational antibody-drug conjugate (ADC). Including patients that reported stable disease as their best response, the ADC controls the progression of the cancer in 75% and 56% of NSCLC and SCLC patients, respectively. These patients had either failed to respond to their last lung cancer therapies or their cancer had returned or progressed.

“Dr. Francois Wilhelm, Chief Medical Officer, presented the updated results at the 15th Annual Targeted Therapies of Lung Cancer Meeting, an invitation-only meeting sponsored by The International Association for the Study of Lung Cancer (IASLC).

“Sacituzumab govitecan is a next generation ADC designed for targeted therapy of solid cancers. The agent was created by site-specifically conjugating a TROP-2-targeting antibody with a high ratio of a moderately toxic drug, SN-38, using a pH sensitive linker. TROP-2 is a receptor found on many human cancer cells, such as cancers of the breast, cervix, colon and rectum, kidney, liver, lung, ovary, pancreas, and prostate, but with only limited expression in normal human tissues. In an animal model of human pancreatic cancer, the ADC delivered up to 135-times the amount of SN-38 to the tumor than when irinotecan, the parent drug of SN-38, was given.”


Surgery for Stage I SCLC Provides Survival Benefit

The gist: A recent study found that people with stage I small cell lung cancer (SCLC) might survive longer if they have surgery to remove part of the lung affected by cancer. The study compared survival rates between patients who had surgery and patients who had other forms of treatment. Five years after treatment, 62% of the patients who had surgery were still alive, compared to 25% of the patients who did not have surgery.

“Patients with stage I limited-disease small cell lung cancer who underwent surgical resection demonstrated a significant survival advantage compared with those who received nonsurgical treatment, according to results of a retrospective study.

“Surgical resection also appeared effective in some patients with stage II or stage II limited-disease small cell lung cancer (LD-SCLC), results showed.

“ ‘Although chemotherapy and radiotherapy are recommended for patients with LD-SCLC, several series have reported favorable survival outcomes even in patients with stage II and stage III disease who underwent surgical resection,’ Tomoyoshi Takenaka, MD,of the department of thoracic oncology at National Kyushu Cancer Center in Fukuoka, Japan, and colleagues wrote.

“In the current study, Takenaka and colleagues analyzed the outcomes of 277 patients aged 38 to 89 years (median, 66 years; 81% men) treated for LD-SCLC from 1974 to 2011 at National Kyushu Cancer Center…

“ ‘Surgical resection provided a survival benefit for the patients with clinical stage I SCLC and some cases of stage II or stage III disease in this study,’ Takenaka and colleagues wrote. ‘The outcomes of treatment for SCLC have been improved beginning in the 2000s. A further prospective study is warranted to clarity the possibility of extending the indications for surgical resection to curatively treat LD-SCLC in the present situation.’ ”


FDA Names New Drug Tarextumab "Orphan Drug" for Small Cell Lung Cancer

The gist: The U.S. Food and Drug Administration (FDA) has granted “orphan drug” designation to a new drug called tarextumab for small cell lung cancer (SCLC) and pancreatic cancer. The designation will make it easier for the drug maker to successfully develop tarextumab and get it to patients in the U.S. Tarextumab has shown promise in patients in a clinical trial. It is given to patients in combination with chemotherapy.

“The US Food and Drug Administration (FDA) has granted orphan drug designation to the OncoMed agent tarextumab for the treatment of pancreatic cancer and lung cancer. Tarextumab (formerly OMP-59R5) is a fully human monoclonal antibody targeting the Notch 2/3 receptors.

“ ‘We are excited to receive two separate orphan drug designations for tarextumab for the treatment of pancreatic and small-cell lung cancer,’ said Paul J. Hastings, OncoMed’s chairman and chief executive officer, in a statement.

“Earlier this month the drug company announced final phase 1b clinical and biomarker data from the ALPINE (Antibody Therapy in First-Line Pancreatic Cancer Investigating Anti-Notch Efficacy and Safety) study, which tested tarextumab in combination with gemcitabine plus nab-paclitaxel in pancreatic cancer.

“Of the 29 patients in the trial, 21 (73%) achieved either a partial response or stable disease with the combination therapy.”


After Promising Early Results, Drug to Continue Testing in More Relapsed SCLC Patients

The gist: In a clinical trial, a new drug called PM1183 showed promise for treating people with small cell lung cancer (SCLC). Based on those results, the drug will be tested in more people in a new phase III clinical trial. PM1183 will be given to patients along with the drug doxorubicin. For comparison, some patients will only be treated with the drug topotecan. The trial will enroll patients who have SCLC that returned (relapsed) after standard treatment.

“Zeltia announces today that its pharmaceutical division PharmaMar will start a Phase III trial with PM1183 in combination with doxorubicin against topotecan in SCLC, given the activity observed in an interim analysis of an ongoing Phase Ib trial. The results of this study will be presented at a prominent international cancer meeting this year, which will be soon announced.

“Patients with small cell lung cancer (SCLC) after failure of standard chemotherapy, as well as bladder, gastric, breast, endometrial or ovarian cancer, neuroendocrine tumors and soft-tissue sarcomas were treated with the combination in a Phase I. The treatment showed efficacy across all cancer types, including several complete responses. This clinical response was remarkable in certain tumor types, particularly in SCLC, and consequently more patients with this type of tumor were enrolled. The treatment was generally well-tolerated, and these patients had marked objective tumor responses and were able to receive several cycles of treatment.

” ‘The data we have are very exciting as patients with SCLC have the worst prognosis among lung cancer patient. There have been no significant advances in 25 years in this type of lung cancer.’ says Luis Mora, Managing Director, PharmaMar.”


New Agent Causes Small Cell Lung Tumors to Shrink in Pre-Clinical Testing

The gist: Scientists are working on a potential new treatment for small cell lung cancer (SCLC) that looks promising in mice, but it has not yet been tested in patients. The drug is called THZ1. In mice, it shrank tumors significantly. It may soon be tested in patients in clinical trials.

“Small cell lung cancer – a disease for which no new drugs have been approved for many years – has shown itself vulnerable to an agent that disables part of tumor cells’ basic survival machinery, researchers at Dana-Farber Cancer Institute and the Massachusetts Institute of Technology reported.

“In a study published today in the journal Cancer Cell, the investigators found that the agent THZ1 caused human-like small cell lung tumors in mice to shrink significantly, with no apparent side effects. The compound is now being developed into a drug for testing in human patients in clinical trials.

” ‘Small cell lung cancer is a disease for which new treatments are desperately needed,’ said Kwok-Kin Wong, MD, PhD, co-senior author of the study and medical oncologist at Dana-Farber. ‘Patients generally respond well to initial chemotherapy, but the disease almost always returns. Less than 5 percent of patients are alive five years after being diagnosed with the disease.’ “


Amrubicin Edges Topotecan for Survival in Refractory SCLC

“Amrubicin failed to improve survival over topotecan as second-line therapy for patients with sensitive small-cell lung cancer (SCLC), according to results of a new randomized phase III trial. There was, however, a small overall survival benefit seen in patients with refractory disease.

“ ‘SCLC is the most aggressive type of lung cancer,’ wrote researchers led by Joachim von Pawel, MD, of Asklepios Fachkliniken München-Gauting in Germany. ‘Despite encouraging phase II results for many targeted therapies and newer chemotherapeutic agents, current large phase III trials have failed to show improvement compared with standard of care.’ Currently, topotecan is the only approved drug for second-line therapy in SCLC patients sensitive to initial treatment; earlier work suggested the third-generation anthracycline and topoisomerase II inhibitor amrubicin could have strong activity in these patients.

“The new study included 637 patients with refractory or sensitive SCLC, assigned 2:1 to amrubicin or topotecan. The median overall survival was 7.5 months with amrubicin and 7.8 months with topotecan, for a hazard ratio of 0.880 (95% CI, 0.733-1.057; P = .170).”