The top three news in Onco-this-Week include Cisplatin’s good show in HPV-positive oropharyngeal cancer and Pembrolizumab showing a complete response rate of approximately 40% in patients with High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC) unresponsive to standard of care. Our trivia section features a QnA on the RECIST guidelines for solid tumor treatments and check out how these guidelines are changing to accommodate immunotherapies. Also featured is the coverage from ESMO 2018 conference organized by European Society for Medical Oncology. – Abhi Dey
- Cisplatin remains standard for low-risk HPV+ oropharyngeal cancer. In today’s world, when cytotoxics have lagged behind targeted agent and immunotherapies, cisplatin came back pretty strongly in low-risk HPV+ oropharyngeal cancer. 300+ patients were randomized to get radiotherapy with either cisplatin or EGFR inhibitor, Cetuximab, which was expected to show improved or same survival rates but better toxicity profiles. However, as per the results announced in ESMO 2018 conference, Cetuximab showed worse OS and added to toxicities. So, no change of SoC here yet!
- CRR of ~40% with Pembrolizumab in high-risk NMIBC patients unresponsive to BCG therapy. Though immunotherapies have already established themselves in metastatic bladder cancer space and more are still coming (read Nivolumab + Ipilimumab combination in heavily pre-treated mBladder Cancer patients), the early stage bladder cancer patients still had fewer options. As per results from Ph II KEYNOTE-057 trial presented in ESMO 2018, Pembrolizumab not only shows the potential to be an emerging option in this patient segment which makes up to 80% of all newly diagnosed bladder cancer cases, it also consolidates its anti-tumor activity as monotherapy in various cancers.
- Missing ‘sting’ in MK-1454 monotherapy data. Merck presented preliminary data of its STING agonist, MK-1454, from Ph I trial in ESMO 2018, and it was not difficult to see why the much-awaited data failed to created a buzz in investors and clinicians. In combination arm with Pembrolizumab, there were still some PRs but the monotherapy arm fared very badly with notable absences of any CRs or PRs. Even in the combination arm, the responders are all PD-(L)1-naive patients – the unmet need in progressors thus remains unfilled.
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REGULATORY NEWS
Compelling data for Lonsurf in metastatic #gastriccancer presented at ESMO 2018 https://t.co/5wttEJIYbR pic.twitter.com/5apFnssnB2
— StomachCancerCa (@StomachCancerCa) October 22, 2018
The sNDA was based on data from randomized, pivotal Ph III TAGS trial evaluating LONSURF versus placebo and BSC in 2L+ metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma patients. The trial met its primary endpoint of improvement in overall survival (OS) and secondary endpoint of improvement in progression-free survival (PFS) with consistent safety and tolerability profile.
$MRK EMA Adopts Positive Opinion for KEYTRUDA® as Adjuvant Therapy in Melanoma https://t.co/lsbMQ7XD8M
— Odi Bruckman (@odibro) October 22, 2018
“There is a growing need for innovative therapies that can help reduce the risk of recurrence following surgery in patients with stage III melanoma,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “Today’s news reflects the collaborative efforts of Merck and EORTC to improve the way we treat melanoma earlier in the treatment paradigm. We look forward to working with European regulatory authorities to bring KEYTRUDA to these patients in the adjuvant setting.”
RESULTS
Ph III ARAMIS trial of AR inhibitor Darolutamide completed in nmCRPC patients – primary endpoint met
SPARTAN vs PROSPER vs ARAMIS Darolutamide(ODM-201) significantly extended metastasis-free survival ,compared to placebo.The safety profile and tolerability has been granted Fast Track by FDA pic.twitter.com/mfFXcORmAZ
— GUO-AEU (@GUOaeu) October 26, 2018
“Prostate cancer is the second most commonly diagnosed malignancy in men in worldwide, and approximately 70 percent of patients have the non-metastatic form of the disease. While conventional hormone therapy is effective in the treatment of non-metastatic cancer, the efficacy is often eventually lost as the sole form of treatment. Additional treatment options in the early stages of the cancer that delay the time to metastases with a manageable safety profile are long awaited. They are significant for the patient’s overall well-being,” says Christer Nordstedt, Senior Vice President, Research and Development at Orion.
Genmab Announces Positive Topline Results in Phase III CASSIOPEIA Study of Daratumumab in Front Line #MultipleMyeloma @Genmab https://t.co/vLBx1ntbsZ pic.twitter.com/eZr0nEjr3R
— Hematopoiesis News (@Hema_News) October 27, 2018
“Having previously seen positive data in the ALCYONE trial, for the frontline treatment of patients ineligible for autologous stem cell transplant, we are very pleased to see the results from the CASSIOPEIA study, which presents exciting insights into the potential of daratumumab for newly diagnosed multiple myeloma patients who received an autologous stem cell transplantation (ASCT). We also look forward to the data from the second part of the study, which will provide further data on the impact of daratumumab monotherapy as maintenance treatment,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
TRIAL STATUSES
“Our team has made three NDA submissions in China this year, including two for zanubrutinib and one for tislelizumab, our investigational anti-PD-1 antibody. We are hopeful that these submissions, if approved, could further transform BeiGene as well as bring important new treatment options to cancer patients,” commented John Oyler, co-founder, CEO and Chairman of BeiGene.
Zanubrutinib Shows Promise in Phase 1 Trial
“The data showed that all patients with CLL/SLL responded to treatment, including 2 complete responses, 6 partial responses, and 1 partial response with lymphocytosis…”https://t.co/G6dKyVmHEW— CLL Ireland (@CllIreland) October 21, 2018
“We are delighted that the submission for zanubrutinib in patients with relapsed/refractory CLL/SLL was accepted by the NMPA in China, and we are excited to announce the top-line pivotal data for zanubrutinib in these patients, which demonstrated a high overall response rate of 80 percent despite a relatively short follow-up. These results in China are also consistent with the data from our global studies,” said Dr. Xiaobin Wu, General Manager of China and President of BeiGene, Ltd.
COLLABORATIONS
Daiichi Sankyo signs clinical trial collaboration deal with Merck and Pfizer: Daiichi Sankyo has entered into a clinical trial collaboration agreement with Merck and Pfizer to evaluate the combination of its [fam-] trastuzumab deruxtecan (DS-8201) with… https://t.co/N83w7zGYxv
— cafepharma (@cafepharma) October 26, 2018
“The collaboration is another milestone in our development strategy to maximize the potential of [fam-] trastuzumab deruxtecan for various HER2 expressing and mutated cancers in combination with immunotherapy and other agents with novel mechanisms of action,” said Tom Held, Vice President, Head, Antibody Drug Conjugate Task Force, Oncology Research and Development, Daiichi Sankyo. “We look forward to working with Merck KGaA, Darmstadt, Germany and Pfizer to determine an appropriate combination strategy to help further improve outcomes for patients. In particular, we are enthusiastic about better understanding the potential of combining [fam-] trastuzumab deruxtecan with DNA damage response agents.”
$IPH.PA Poster: Phase II study of monalizumab, a first-in-class NKG2A monoclonal antibody, in combination with cetuximab in previously treated recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) #ESMO18 pic.twitter.com/9Y2DTG40go
— Tom Silver (@TomSilver39) October 20, 2018
Pascal Soriot, Chief Executive Officer, said: “Our expanded collaboration with Innate Pharma enables us to further strengthen our leadership in immuno-oncology, and to explore the potential of next-generation immuno-oncology pathways, together with the world-class scientific team of Innate. Today’s agreement also secures the long-term commercialisation of the recently FDA approved rare disease medicine, Lumoxiti, through dedicated focus and investment by Innate Pharma.”
HIGHLIGHTS FROM ESMO 2018
Cisplatin remains standard for low-risk HPV+ oropharyngeal cancer
Tesaro presents updates from GARNET, PRIMA and QUADRA trials
Zoledronic acid improves DFS in premenopausal HR+ early breast cancer in Ph III HOBOE-2 trial
Updated results for bifunctional immunotherapy M7824
Sitravatinib’s activity in CBL mutation positive NSCLC and melanoma patients in Ph Ib trial
Disappointing mid-stage data in Ph II trial with Sitravatinib + Nivolumab; just 16% confirmed RRs
OS benefit confirmed with Palbociclib combo in pretreated HR+/HER2- breast cancer
Alpelisib combo nearly doubles PFS in PIK3CA-mutant breast cancer in Ph III SOLAR-1 trial
Q: What is RECIST?
A: RECIST (Response Evaluation Criteria In Solid Tumors) guideline provides a simple and practical set of instructions to assess the activity and efficacy of new cancer treatment in solid tumors, using validated and consistent criteria to assess changes in tumor burden by clearly defining when patients are analyzed to have improved (“responded“), stayed the same (“stable“) or worsened (“progressed“) during the course of or at the end of treatment.
Q: When RECIST guidelines were first formed?
A: The original RECIST criteria were published in February 2000 by an international collaboration between European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute (NCI) of the United States and the National Cancer Institute of Canada Clinical Trials Group to provide harmonisation of tumour response assessment.
Q: Were RECIST guidelines updated over years?
A: RECIST 1.1, published in January 2009, was an update to the original RECIST criteria. Today, the majority of clinical trials evaluating efficacy of cancer treatments in solid tumors are using RECIST.
Q: What are iRECIST guidelines?
A: The iRECIST guidelines address immunotherapies, ensuring consistent trial design and interpretation of tumour progression measurements for immunomodulating drugs.
Q: Why were iRECIST guidelines needed?
A: Immunotherapies are distinctive from traditional therapeutics modalities in several aspects, like delayed responses after pseudoprogression. iRECIST guidelines describes a standard approach to solid tumour measurement and definitions for objective change in tumour size which can be used in clinical studies of immunotherapeutic drugs.
SOURCE: http://www.irrecist.com/recist/
About the Author:
Richa earned her PhD at the National Brain Research Centre, India. For her thesis, she worked on the dreaded Glioblastoma multiforme. That was her first in-depth exposure to academic research in cancer biology. After her PhD, she expanded her research experience by working in the field of immunology at UCLA, USA. After her return to India, Richa switched to a corporate setting but continued her engagement with the cancer field. She is currently loving her work, which affords her the opportunity to continue developing her knowledge in the biomedical field of cancer. Outside of work, she enjoys watching, identifying and photographing birds.
Editor and Blog Design:
Abhi graduated from the Molecular Biophysics Unit of IISc (Bangalore, India) in 2011. As a Biomedical Scientist, he has worked with all three life-forms in his 13-year research career, viz., particulate, unicellular and multicellular. He is currently an Assistant Scientist at Emory University (Atlanta, GA) studying mechanisms of tumor recurrence in kids with brain tumors. As a postdoctoral fellow, he was the recipient of two Young Investigator Awards from Alex Lemonade Stand Foundation (Philadelphia, PA) and Rockland Immunochemicals. His current research has been funded by Northwestern Mutual Foundation (Milwaukee, WI), CURE Childhood Cancer Foundation (Atlanta, GA) and American Association for Cancer Research (AACR). When he is not on the bench you will find him spending time with his family or exploring the world through traveling and blogging.
Image Sources: Wikipedia and Twitter
Cover image: (CellImageLibrary) Confocal micrograph of lesions in human cervical epithelium infected with human papilloma virus (HPV16). Early viral proteins (green) bind to and re-orgainse the ketatin filaments (red) towards the edge of the cell. Cell nuclei are stained with Dapi (blue).– Source
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