ASCO 2017: I-SPY 2 Trial: Combination of Pembrolizumab Plus Standard Neoadjuvant Therapy in High-Risk Breast Cancer


“At the 2017 ASCO Annual Meeting, results were presented from the phase II I-SPY 2 trial investigating pembrolizumab (Keytruda) in combination with standard therapy (paclitaxel followed by doxorubicin and cyclophosphamide) as a neoadjuvant treatment for patients with locally advanced triple-negative breast cancer or hormone receptor–positive/HER2-negative breast cancer (Abstract 506).

“Findings showed that the addition of pembrolizumab increased the estimated pathologic complete response rate nearly threefold in patients with triple-negative breast cancer (60% vs 20%) and in patients with hormone receptor–positive/HER2-negative breast cancer (34% vs 13%) compared to standard therapy. Overall, based on Bayesian predictive probability of success in a confirmatory phase III trial, pembrolizumab has graduated from the I-SPY 2 TRIAL for all signatures in which it was tested (triple-negative breast cancer, all HER2-negative, and hormone receptor–positive/HER2-negative).”

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Small Cell Lung Cancer at ASCO: Some Welcome News

Small cell lung cancer (SCLC) is a fatal disease that has not seen new drug approvals for the last 17 years. Considering the relative success of ‘immune checkpoint inhibitors’ in non-small cell lung cancer (NSCLC), it is not surprising that several abstracts recently presented at the 2015 American Society of Clinical Oncology (ASCO) annual meeting were devoted to clinical trials testing these trendy, immune system-boosting drugs in people with SCLC. Continue reading…

PharmaMar's Investigational Drug PM1183 plus Doxorubicin Shows Remarkable Activity in Small Cell Lung Cancer

“PharmaMar today announced data from a Phase 1b study of the transcriptional inhibitor PM1183 in combination with doxorubicin in second line therapy in patients with small cell lung cancer (SCLC) showing that the treatment induced objective responses in 67% of the patients, including 10% of them where all signs of cancer disappeared (complete responses). Every patient with SCLC denominated primary chemotherapy-sensitive (their chemotherapy-free interval (CTFI) is more than 90 days) responded to treatment, including 18% of complete responses. In primary chemotherapy-resistant patients, where cancer was progressing within 90 days or less of previous chemotherapy, a remarkable 30% achieved a response. Notably, the treatment resulted in durable responses, with an overall progression-free survival (PFS) of 4.6 months, which was 3.6 months in resistant patients. The most common adverse drug reaction was reversible myelosuppresion but no cardiotoxicity or drug-related deaths were observed.

“ ‘The rate, depth and length of responses that we have observed with this treatment in the second-line setting are remarkable, even in those patients that are usually considered harder to treat”, said Dr. Martin Forster, University College Hospital, London, UK.

“ ‘Small cell lung cancer is an unmet clinical need with very few recent advances and the scientific community is committed to help new develop effective therapies.’ ”

MM-302 Shows Promise in Heavily Pretreated HER2-Positive Breast Cancer

“A phase I study of MM-302, an antibody-drug conjugated human epidermal growth factor receptor 2 (HER2)-targeted liposomal doxorubicin, as a monotherapy or in combination with trastuzumab or trastuzumab and cyclophosphamide had a manageable safety profile and encouraging efficacy results in a group of heavily pretreated women with HER2-positive metastatic breast cancer.

“The results of the study were presented by Patricia LoRusso, DO, professor of medicine in the division of oncology at Yale University in New Haven, Connecticut, at the American Association for Cancer Research (AACR) Annual Meeting.

“Patients in the study who received at least 30 mg/m2 of MM-302 plus trastuzumab had a median progression-free survival of 7.6 months (95% confidence interval [CI], 3.6–10.9); those treated with the addition of cyclophosphamide had a median progression-free survival of 10.6 months (95% CI, 1.8–10.6).

“ ‘We are encouraged by these data on the safety and promising clinical activity of MM-302 in patients who have exhausted many therapeutic options for their disease. Our results support the further evaluation of MM-302 in an anthracycline-naive population in the HERMIONE trial,’ said LoRusso in a prepared statement.”

Early Access Program to Make ThermoDox Available in Europe for Patients with Recurrent Chest Wall Breast Cancer

The gist: Patients with recurrent chest wall (RCW) breast cancer in the European Union and Switzerland will now have access to a new treatment called ThermoDox. ThermoDox is a new way of delivering the chemotherapy drug doxorubicin. ThermoDox is spread throughout the body by the bloodstream, but it is not activated unless a doctor heats a body part to 39.5 – 42 degrees Celsius. That way, the patient can have the drug activated only to the part of the body where it is needed. Based on promising results in patients in clinical trials, ThermoDox will now be available in Europe in an Early Access Program.

“Celsion Corporation (NASDAQ:CLSN), a fully-integrated oncology company focused on the development of a portfolio of innovative cancer treatments,  today announced that it has signed a license and distribution agreement with myTomorrows to implement an Early Access Program for ThermoDox®, its proprietary heat-activated liposomal encapsulation of doxorubicin, in all countries of the European Union (EU) territory plus Switzerland for the treatment of patients with recurrent chest wall (RCW) breast cancer.

“RCW breast cancer is difficult to treat and has a poor prognosis with a significant impact on a patient’s quality of life.  Patients with highly resistant tumors found on the chest wall often see their cancer progress despite previous treatment attempts including chemotherapy, radiation therapy and hormone therapy.  There are approximately 25,000 to 35,000 incidence of RCW breast cancer in the EU alone and thermal therapy is a well-accepted strategy for treating patients.  Recent findings from two Phase I studies and an ongoing open label Phase II study indicate that when combined with thermal therapy, ThermoDox can demonstrate significant overall response rates and tumor control in post mastectomy, refractory patients.”

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.”

Four Cycles of FEC Chemotherapy Are as Good as Six Cycles in Node-Negative Breast Cancer

The gist: A recent clinical trial showed that people with node-negative breast cancer did just as well on a shorter, four-week chemotherapy treatment as people who took a longer, six-week one. The shorter treatment consisted of four cycles of doxorubicin and cyclophosphamide. The longer one involved six cycles of 5-fluorouracil, epirubicin and cyclophosphamide. Patients in both groups had similar survival rates, and people in the longer treatment group had worse side effects.

“Patients with node-negative breast cancer who received six cycles of 5-fluorouracil, epirubicin and cyclophosphamide experienced similar DFS and OS as patients who received four cycles of doxorubicin and cyclophosphamide, according to results of a phase 3 study presented at the San Antonio Breast Cancer Symposium.

“ ‘[In the MA-5 trial, the NCIC Clinical Trials Group] administered a dose-intensified epirubicin program, and the RFS and OS results were encouraging,’ Charles Edward Geyer, Jr., MD, FACP, associate director for clinical research at Virginia Commonwealth University Massey Cancer Center, said during his presentation. ‘Additionally, the French Adjuvant Study Group around that time had also evaluated their standard adjuvant regimen of FEC-50 and had shown that six cycles of therapy were more effective than three. So, at that time, we had two separate trials looking at different epirubicin schedules, both of which had seemed to be positive. It seemed reasonable at that time to compare [doxorubicin and cyclophosphamide] with one of those regimens. Since we were going to conclude the study in node-negative patients and include post-menopausal women, we chose the FEC-100 [chemotherapy regimen] because of its improved toxicity profile…’

“ ‘[Six cycles of] FEC-100 did not improve the primary endpoint of DFS or our secondary endpoint of OS relative to [four cycles of] AC,’ Geyer said. ‘Toxicities were increased with the FEC-100, which wasn’t unexpected because it did administer additional cycles of therapy compared with AC. Overall, the results do not support the use of six cycles of anthracycline-based regimens in node-negative breast cancer.’ “

Aldoxorubicin Receives FDA Orphan Drug Designations for Glioblastoma, Small Cell Lung Cancer, and Ovarian Cancer

The gist: When a newly developed drug for a rare (“orphan”) disease seems particularly promising for patients, the U.S. Food and Drug Administration (FDA) may choose to grant it “orphan drug designation.” The designation removes certain barriers that might otherwise keep a drug company from being able to successfully develop and profit from the drug in the U.S. A new drug called aldoxorubicin has just received an orphan drug designation for the treatment of small cell lung cancer (SCLC), glioblastoma multiforme, and ovarian cancer. Aldoxorubicin is a special version of the chemotherapy drug doxorubicin. It allows for higher doses of doxorubicin with fewer side effects.

“The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designations to aldoxorubicin in three indications: glioblastoma multiforme, small cell lung cancer, and ovarian cancer. Aldoxorubicin combines doxorubicin with a novel single-molecule linker that binds directly and specifically to albumin, allowing greater doses of the chemotherapeutic agent to be administered while reducing its toxic side effects.

“Aldoxorubicin is currently being studied in a global phase III clinical trial evaluating the efficacy and safety of aldoxorubicin as a second-line treatment for patients with soft-tissue sarcoma. CytRx, a biopharmaceutical research and development company, is also evaluating aldoxorubicin in two phase II clinical trials, one in patients with late-stage glioblastoma multiforme and the other in HIV-related Kaposi’s sarcoma. A global phase IIb trial in patients with relapsed small cell lung cancer is expected to commence later this month, and the company is undertaking a phase Ib combination study of aldoxorubicin plus gemcitabine as a potential precursor to a trial in relapsed ovarian cancer.”

Celsion Announces Enrollment of First Patient in Global Phase III OPTIMA Study of ThermoDox® in Primary Liver Cancer

Editor’s note: This article is about a new clinical trial—a research study with volunteer patients. The goal of the trial is to test the effectiveness of a new liver cancer treatment. The treatment combines the drug ThermoDox with a procedure called radiofrequency ablation (AFA). It is meant for people with hepatocellular carcinoma (HCC). The trial has enrolled its first participating patient, and will enroll a total of 550 patients at sites in North America, Europe, China, and Asia Pacific.

“Celsion Corporation (NASDAQ: CLSN), an oncology drug development company, today announced that the first patient has been enrolled in its pivotal Phase III OPTIMA Study of ThermoDox® in combination with optimized radiofrequency ablation (RFA) in patients with primary liver cancer, also known as hepatocellular carcinoma (HCC).  ThermoDox® is Celsion’s proprietary, heat-activated, liposomal encapsulation of doxorubicin.

” ‘There is an urgent need for new treatment options that address primary liver cancer, a rapidly progressing disease with a poor prognosis whose worldwide incidence is growing at an alarming rate,’ stated Won-Young Tak, M.D., Ph.D. at the Kyungpook National University Hospital in South Korea and Asia Pacific Principal Investigator for the OPTIMA Study. ‘The OPTIMA Study builds on extensive clinical and preclinical data that point to the potential of ThermoDox®, when combined with an optimized RFA regimen, to significantly improve patient outcomes. I look forward to working with my colleagues to further explore the clinical utility of ThermoDox® in this setting.’ “