Phase 1/2 Data Combining Urelumab with Opdivo (Nivolumab) in Hematologic and Solid Tumors Suggest Increased Antitumor Effect in Patients with Melanoma

Excerpt:

Bristol-Myers Squibb Company BMY -0.86% today announced safety and efficacy data from a Phase 1/2 study of urelumab in combination with Opdivo (nivolumab) in patients with hematologic and solid tumors, including biomarker analyses by level of PD-L1 expression. The combination of urelumab and Opdivo showed encouraging efficacy among 46 evaluable melanoma patients with an objective response rate (ORR) of 50% (23/46 with 18 confirmed and 5 unconfirmed). ORR was a secondary endpoint as measured by Response Evaluation Criteria In Solid Tumors (RECIST). Similar response was seen in both PD-L1 positive and PD-L1 negative melanoma patients, with ORR of 50% (10/20) and 47% (8/17) in those with greater-than or equal to 1% and <1% PD-L1 expression, respectively. Among the other cohorts (n=78), one non-small cell lung cancer (NSCLC) patient and one squamous cell carcinoma of the head and neck (SCCHN) patient had an objective response. In the full patient population (n=138), no significant added toxicity was observed with urelumab in combination with Opdivo over Opdivo monotherapy. These data were presented at an oral presentation (poster number 239) at the Society for Immunotherapy of Cancer (SITC) 31 Annual Meeting on November 12 at 10:40 a.m. EST in National Harbor, Maryland.”

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Investigational AKT Inhibitor AZD5363 is Active Against Multiple Tumor Types With AKT1 E17K Mutations

“Treatment with the investigational pan-AKT inhibitor AZD5363 led to tumor regression in patients with a variety of types of solid tumors positive for the AKT1 E17K genetic mutation, according to data from a phase I clinical trial expressly designed to recruit patients with these types of tumors. The data were presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Nov. 5–9.

“ ‘The AKT1 E17K genetic mutation was detected in a range of tumor types almost 10 years ago,’ said David M. Hyman, MD, acting director of developmental therapeutics at Memorial Sloan Kettering Cancer Center in New York. ‘Because the mutation is found in only a small fraction of cases of each tumor type and clinical trials have traditionally enrolled patients with only one type of cancer, it was not possible to determine whether the mutation fuels the growth of these tumors and is a viable therapeutic target until the recent advent of basket trials, whereby patients with a range of types of tumor all harboring a defined mutation are enrolled in a single clinical trial.’ “


The CAR T-Cell Treatment: Will It Work for Solid Tumors?


Chimeric antigen receptor (CAR) T-cell therapy is a new, immune system-based cancer treatment that has garnered recent media attention. In a clinical trial, CAR T-cell treatment left no signs of tumors in 70% to 90% of children and adults with the aggressive blood cancer acute lymphocytic leukemia (ALL). ALL is almost always fatal, and the results observed with CAR T-cell treatment are nothing short of spectacular. Continue reading…


Tests for New Cancer Drugs Not Reliable Enough, Doctors Say

“Drugmakers including Bristol-Myers Squibb Co and Merck & Co are testing which patients will most benefit from new cancer treatments based on a protein found in their tumors, but that guide, known as a biomarker, may be too unreliable, researchers and health experts said.

“Bristol’s Opdivo and Merck’s Keytruda are both therapies designed to block a protein known as Programmed Death receptor (PD-1) that tumors use to evade the body’s natural defenses. Competitors Roche Holding, AstraZeneca and Pfizer also have similar drugs in an earlier stage of development. The drugmakers are conducting clinical trials that test patient tumors for a related protein called PD-L1.

“The new drugs are mainly aimed at patients with so-called solid tumors suffering from diseases including lung cancer and liver cancer. Lung cancer, the most common type, claims 1.8 million new cases each year worldwide. Sales of drugs to block PD-1 could reach $33 billion a year by 2022, according to Morningstar.”


New Drug for Advanced HER2-Positive Breast Cancer Begins Testing in a Clinical Trial

The gist: A clinical trial has begun to test a new treatment for people with HER2-positive breast cancer. The drug is called SYD985. It is being tested in people with locally advanced or metastatic tumors. The first phase of testing will enroll both HER2-positive and HER2-negative cancer patients to test the safety of the drug. The second phase will enroll HER2-positive breast and gastric cancer patients, including patients with low expression of HER2 (HER2 2+).

“Synthon Biopharmaceuticals (‘Synthon’) today announced that the first patients with metastatic solid tumors have commenced treatment with its investigational anti-HER2 antibody-drug conjugate (ADC), SYD985.

“First patients for this trial are being enrolled in leading European oncology centers Radboud University Medical Center (Nijmegen, the Netherlands), the Jules Bordet Institute (Brussels, Belgium) and the Institute of Cancer Research at The Royal Marsden Hospital (London, United Kingdom). The trial will recruit at least 76 patients and more centers are expected to join the trial in 2015.

“This trial is a two part first-in-human Phase I study. In the dose escalation part of the trial, safety and efficacy of SYD985 will be evaluated in patients with locally advanced or metastatic solid tumors of any origin. In the expanded cohort part of the trial, only patients with breast and gastric cancer will be enrolled. The expanded cohorts will include patients currently indicated for HER2-targeted treatment as well as patients with HER2 2+ and HER2 1+ breast cancer for whom there currently is no effective anti-HER2 therapy available.”


New Ways to Treat Solid Tumours

Editor’s note: Recent research has uncovered a potential new way to fight some cancer types. The key is a protein called Eph3A, which is made by the cells of blood cancers and solid tumors. Researchers made a new drug called KB004 to target and kill cells with Eph3A. The drug is currently being tested in a clinical trial with volunteer leukemia patients.

“An international team of scientists has shown that an antibody against the protein EphA3, found in the micro-environment of solid cancers, has anti-tumour effects.

“As EphA3 is present in normal organs only during embryonic development but is expressed in blood cancers and in solid tumours, this antibody-based approach may be a suitable candidate treatment for solid tumours…

“Currently, KaloBios Pharmaceuticals is testing the anti-EphA3 antibody KB004 in a multi-centre Phase I/II clinical trial in Melbourne and the US in patients with EphA3 expressing blood malignancies: AML, MDS and myelofibrosis.”


Novel Drug Action Against Solid Tumors Explained

Editor’s note: This article describes new research that shows how a drug called ADI-PEG20 targets and kills cancer cells. ADI-PEG20 is currently being studied in clinical trials with volunteer patients who have melanoma, liver cancer, and prostate cancer.

“Researchers at UC Davis, City of Hope, Taipai Medical University and National Health Research Institutes in Taiwan have discovered how a drug that deprives the cells of a key amino acid specifically kills cancer cells.

“Their paper, published today in Proceedings of the National Academy of Sciences, is the culmination of nearly a decade of research into the role of arginine – and its deprivation – in the generation of excessive autophagy, a process in which the cell dies by eating itself…”

“Primo Lara, UC Davis oncologist and associate director of translational research at the cancer center, led a phase I study of the drug in patients with advanced lung, prostate and oral cancers. He reported that combined with a chemotherapy agent, the drug was feasible and reasonably tolerated. He is currently recruiting advanced prostate cancer patients for a new phase I trial of the drug combination.”


Ignyta Announces Initiation of STARTRK-1 Global Phase I/II Clinical Trial of RXDX-101

The gist: Researchers are conducting a clinical trial with volunteer patients to test a new cancer treatment called RXDX-101. RXDX-101 is meant to treat cancer patients whose solid tumors have mutations in the genes TrkA, ROS1, or ALK. The clinical trial is enrolling adults with locally advanced or metastatic cancer with those mutations. 

“Ignyta, Inc. (Nasdaq: RXDX), an oncology precision medicine biotechnology company, today announced the multicenter initiation of the company’s global Phase I/II clinical trial of RXDX-101, its proprietary oral tyrosine kinase inhibitor targeting multiple solid tumor indications. This clinical trial is called STARTRK-1, which stands for Study Targeting ALK, ROS1 or TRKA/B/C, and is a Phase I/IIa, multicenter, single-arm, open-label clinical trial of continuous daily dosing of oral RXDX-101 in adult patients with locally advanced or metastatic cancer confirmed to be positive for relevant molecular alterations.

” ‘We are excited to be able to expand the clinical dosing of this product candidate to patients at leading cancer centers in the U.S., Europe and Asia,’ said Jonathan Lim, M.D., Chairman and CEO of Ignyta. ‘The initiation of the STARTRK-1 trial builds on the momentum of our presentation of interim data from the ongoing RXDX-101 Phase I clinical trial at the ASCO annual meeting, where we reported partial responses in patients with each of TrkA, ROS1 and ALK alterations, as well as in three different tumor types.’ “


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.