Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

Organoid Personalized Therapeutics and the Pancreatic Adenocarcinoma Signature Stratification for treatment (PASS) – 01 trial

Keywords: pancreatic cancer, patient-derived organoids, transcriptomic signatures, PASS-01 Background: Patients with advanced pancreatic ductal adenocarcinoma (PDAC) continue to have a dire prognosis and only a minority of patients is fit enough to receive second-line treatment. Using patient-derived organoids (PDOs), we have identified transcriptomic signatures of chemotherapy sensitivity that may be able to stratify patients such that they receive maximal benefit from the currently approved, first-line chemotherapy regimens [1-3]. We will now test this hypothesis in the Pancreatic Adenocarcinoma Signature Stratification for treatment (PASS) – 01 trial, which is a multi-institutional randomized phase II trial between FOLFIRINOX (mFFX) and gemcitabine/nab-paclitaxel (GA). Methods: The overall aim of PASS-01 is to evaluate biomarkers and gene signatures that may predict response to mFFX and GA. The primary objective is to determine the progression free survival (PFS) benefit of mFFX compared to GA. Using 1:1 randomization, 131 evaluable patients with untreated metastatic PDAC will be recruited to provide 80% power to detect a 2-month improvement in PFS with mFFX (one-sided alpha 0.2). Secondary and exploratory objectives include determine the objective response rate, duration of response and overall survival associated with mFFX or GA, whether the chemotherapy sensitivity signature predictions correlate with responders, if PDO transcriptomic profiles parallel those obtained from patient samples, whether GATA6 expression can serve as a biomarker of response [4], the use of serial cell free circulating tumor DNA and circulating tumour cell analysis to identify emerging or de novo resistance and evaluate biomarkers of immune-oncologic sensitivity. The main inclusion and exclusion criteria are similar to major efficacy trials, with the mandatory requirement that a minimum of 4 x 18G good quality tumour core biopsies can be safely obtainable under CT or US guidance. At progression, as per RECIST 1.1 criteria, chemotherapy sensitivity signatures (RNA) and/or PDO pharmacotyping and WGS data will be used where possible to guide second-line therapy in an effort to continually provide the most active therapeutic regimens to each patient. The trial is anticipated to open Q4 2020. Conclusions: PASS-01 will provide candidate biomarkers and gene signatures that predict response to mFFX and GA, which will be further investigated in a subsequent adaptive, stratified trial

AACR calls on congress to take immediate action against COVID-19 and protect patients with cancer during the pandemic

On March 30, 2020, the AACR Board of Directors provided a letter to the U.S. Congressional leadership on behalf of its members in response to the COVID-19 public health emergency.SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe