NivoPlus Clinical Trial Currently Recruiting Patients With Advanced Cancer

“The Cancer Treatment Centers of America (CTCA) at Western Regional Medical Center in Arizona recently started a Phase Ib/II clinical trial called NivoPlus (NCT02423954) to test a new investigational immunotherapeutic treatment for several advanced cancers. This novel immunotherapeutic approach is based on the combination of an immunotherapy drug (nivolumab) with chemotherapy drugs (irinotecan, temsirolimus and a combination of irinotecan and capecitabine) which have been approved by the U.S. Food and Drug Administration (FDA).

“Cancer immunotherapy is defined as the use of the body’s own immune system to help fight cancer. In 2013, the renowned Science magazine established that cancer immunotherapy had been the scientific breakthrough of the year, and recent advances in the field have yielded promising results for cancer patients.

“Nivolumab is an antibody against the programmed death 1 (PD-1) receptor, an immune checkpoint that if inhibited results in the stimulation of the body’s antitumor immunity. Nivolumab has been approved by the FDA for the treatment of advanced melanoma in December 2014 and metastatic squamous non-small cell lung cancer in March 2015. Its combination with chemotherapeutic drugs is expected to activate the body’s immune system and improve the response to cancer.”


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.’ “


Puma Biotechnology Cancer Drug Shows Positive Mid-Stage Results

The gist: Researchers tested a new lung cancer treatment in a clinical trial—a research study with volunteer patients. The treatment combines the drugs PB272  and temsirolimus. The results were modest; patients who took the combo experienced about four months without their cancer worsening, while patients who took only PB272 went for three months without worsening.

“Puma Biotechnology Inc said its experimental lung cancer drug was safe to be administered with an already approved treatment for the disease in a mid-stage study.

“The time where a patient’s disease did not progress increased to four months when given a combination of Puma’s PB272 and temsirolimus, compared to about three months when given only PB272, according to data from the study.

“All the patients in the study were given a high dose of the drug loperamide to prevent diarrhea related to PB272.

“There were no severe diarrhea events seen in the trial, the company said.”


Promising Results Shown with Targeted Approaches in Subsets of Non-Small Cell Lung Cancer

The gist: Two new targeted treatment approaches are showing promise for some lung cancer patients. Researchers are testing the targeted drug dabrafenib in a clinical trial—a research study with volunteer patients. Dabrafenib is meant to treat certain people who have already been treated for advanced non-small cell lung cancer (NSCLC) but who need additional treatment. The patients who participated in the trial had a tumor mutation called BRAF V600E. The study results supported dabrafenib as an effective treatment for these patients. In another clinical trial, researchers found that a combination of the drugs temsirolimus and neratinib had beneficial effects for people with advanced non-small cell lung cancer (NSCLC) whose tumors had mutations in the HER2 gene.

“The BRAF inhibitor dabrafenib has significant anti-tumour activity in patients with advanced BRAF V600E mutant non-small cell lung cancer whose disease has progressed after chemotherapy, according to phase II data presented at the ESMO 2014 Congress in Madrid, Spain.

” ‘Reports of lung cancers bearing mutations in BRAF have generated considerable interest because these mutations may be associated with increased sensitivity to BRAF tyrosine-kinase inhibiting agents,’ says lead author Dr David Planchard, pulmonary oncologist at the Gustav-Roussy Cancer Campus, Paris, France.

“Planchard says studies suggest that activating BRAF mutations are present in around 2% of lung carcinomas — approximately 80% of which are V600E mutations. The BRAF V600E mutations are frequently associated with shorter disease-free, overall survival, and lower response rates to platinum-based chemotherapy.

“This open-label phase II study involves patients with BRAF V600E mutant non-small cell lung cancer, treated with dabrafenib alone (150 mg, twice daily). The primary endpoint is investigator-assessed overall response rate, with secondary endpoints of progression-free survival, duration of response, overall survival, safety and tolerability, and population pharmacokinetics.”


mTOR Inhibitors May Be Associated with Kidney Injury

A class of cancer drugs called mTOR inhibitors may produce kidney toxicity in at least some patients. mTOR inhibitors, including rapamycin (sirolimus/Rapamune), temsirolimus (Torisel), everolimus (Afinitor), and ridaforolimus, are used to treat certain forms of breast and kidney cancer, and are under investigation for several other cancers. Researchers described four cases of patients treated with mTOR inhibitors developing severe acute kidney injury. They recommend that doctors carefully monitor kidney function in patients receiving these drugs. However, other experts emphasize that it is unclear whether the mTOR inhibitors were indeed the cause of the kidney injury. In at least one case, the patient was also taking other drugs known to cause kidney toxicity.


mTOR Inhibitors May Be Associated with Kidney Injury

A class of cancer drugs called mTOR inhibitors may produce kidney toxicity in at least some patients. mTOR inhibitors, including rapamycin (sirolimus/Rapamune), temsirolimus (Torisel), everolimus (Afinitor), and ridaforolimus, are used to treat certain forms of breast and kidney cancer, and are under investigation for several other cancers. Researchers described four cases of patients treated with mTOR inhibitors developing severe acute kidney injury. They recommend that doctors carefully monitor kidney function in patients receiving these drugs. However, other experts emphasize that it is unclear whether the mTOR inhibitors were indeed the cause of the kidney injury. In at least one case, the patient was also taking other drugs known to cause kidney toxicity.


mTOR Inhibitors May Be Associated with Kidney Injury

A class of cancer drugs called mTOR inhibitors may produce kidney toxicity in at least some patients. mTOR inhibitors, including rapamycin (sirolimus/Rapamune), temsirolimus (Torisel), everolimus (Afinitor), and ridaforolimus, are used to treat certain forms of breast and kidney cancer, and are under investigation for several other cancers. Researchers described four cases of patients treated with mTOR inhibitors developing severe acute kidney injury. They recommend that doctors carefully monitor kidney function in patients receiving these drugs. However, other experts emphasize that it is unclear whether the mTOR inhibitors were indeed the cause of the kidney injury. In at least one case, the patient was also taking other drugs known to cause kidney toxicity.


Clinical Activity and Safety of Combination Therapy with Temsirolimus and Bevacizumab for Advanced Melanoma: A Phase II Trial (CTEP 7190/ Mel47)

A CTEP-sponsored phase II trial was performed to evaluate safety and clinical activity of combination therapy with CCI-779 (temsirolimus) and bevacizumab in patients with advanced melanoma…”