Scientists Simplifying Science

Search
Close this search box.
Donate
Facebook Twitter Instagram Linkedin
Club SciWri header
Search
Close this search box.

Onco-this-Week

SHARE THIS

HIGHLIGHTS

  1. BMS’s voluntarily withdrawal of U.S. application for Nivolumab + low-dose Ipilimumab in 1L NSCLC patients with TMB ≥10 mut/Mb: BMS announced OS data in this subgroup from Checkmate-227 trial in Oct 2018, prompting FDA to extend the review period by three months and move PDUFA date to May 20, 2019. However, as per recent discussions with FDA, BMS thinks the OS data in PD-L1+ patients, which could help elucidate the correlation between PD-L1 and TMB, would not be ready by then. It hence withdrew the application. It was a surprising move by BMS, even when TMB as a biomarker was yet to be established conclusively in the area of cancer therapy.

 

  1. Ramucirumab improves overall survival in AFP-high 2L HCC patients: We have already talked about how Sorafenib dominates the treatment landscape of frontline HCC patients. And how these patients, once they become refractory on Sorafenib, suddenly have fewer options upon their progression in second line. A recent publication citing OS improvement with Ramucirumab brings good cheer, however, it should be noted that better OS improvement (3.5 months) is seen in metanalysis of patients with AFP-high REACH and REACH-2 trials versus OS in patient from current REACH-2 trial alone (1.2 months).

 

  1. GlaxoSmithKline completes acquisition of TESARO: With this acquisition, GSK is getting in the so-called ‘PARP battle’ with AstraZeneca by placing Niraparib against Olaparib. However, Niraparib is not all GSK gets – it is also getting dostarlimab (TSR-042), a PD-1 inhibitor in Ph III testing; Ph I therapy TSR-022, a mAb against T cell immunoglobulin and mucin domain 3 (TIM3; HAVCR2); and a Ph I compound TSR-033, a mAb against lymphocyte-activation gene 3 (LAG3; CD223).

This edition of Onco-this-Week is Sponsored by

North America Immigration Law Group & Nano-Tag Biotechnologies

 

 

 

DRUG APPROVALS

Rucaparib approved in EU as maintenance therapy in relapsed ovarian cancer patients based on Ph III ARIEL3 trial results


“This EC authorization of rucaparib is an important step in ensuring that it is available to all women who may potentially benefit, regardless of their BRCA status,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “We believe that access to maintenance treatment is extremely important for women with relapsed platinum-sensitive ovarian cancer, and we are pleased that rucaparib can now be an option for these women. As the only PARP inhibitor that has shown further tumor shrinkage as well as prolonged progression-free survival in this maintenance setting, we believe Rubraca represents an important step forward for women with advanced ovarian cancer.”

 

REGULATORY NEWS

BMS voluntarily withdraws U.S. application for Nivolumab + low-dose Ipilimumab in 1L NSCLC patients with Tumor Mutational Burden ≥10 mut/Mb


BMS announced OS data in this subgroup from Checkmate-227 trial in Oct 2018, prompting FDA to extend the review period by three months and move PDUFA date to May 20, 2019. However, as per recent discussions with FDA, BMS thinks the OS data in PD-L1+ patients, which could help elucidate the correlation between PD-L1 and TMB, would not be ready by then. It hence withdrew the application.

 

Breakthrough therapy designation granted to Umbralisib in CD20 inhibitor-treated MZL based on Ph IIb UNITY-NHL trial data


Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, “We look forward to working closely with the FDA to bring umbralisib, our novel PI3K-delta inhibitor to patients as quickly as possible. MZL patients who fail initial chemo-immunotherapy are left with limited treatment options. We believe umbralisib can play an important role in fulfilling this unmet medical need. The MZL single agent umbralisib cohort of the UNITY-NHL study is fully enrolled and we look forward to reporting top-line results from this cohort by mid-year and presenting the data at a major medical meeting in 2019.”

 

sBLA filed for Daratumumab + Lenalidomide + Dexamethasone in 1L transplant-ineligible multiple myeloma patients based on Ph III MAIA data


“We are encouraged that the submission for daratumumab in combination with lenalidomide and dexamethasone has begun, with a potential for the regimen to be approved earlier for US patients,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

 

CTA approval granted for initiation of Ph I/II trial of clonal neoantigen T cells (cNeT) in NSCLC pts in UK

“Approval of our first CTA represents an important validation of our approach and a significant milestone for Achilles,” said Dr Iraj Ali, CEO of Achilles Therapeutics. “Achilles was founded by world-leading experts in cancer evolution, bioinformatics and the delivery of cell-based immunotherapies and we are bringing together these disciplines to develop next-generation, patient-specific T cell therapies that harness the immune system to destroy cancer cells.”


“The Achilles approach is a technological step forward in the immune-oncology space with the potential to bring the next wave of revolutionary new immunotherapies to cancer patients,” said Dr Martin Forster, Chief Investigator for the study at University College London Hospitals (UCLH), the lead clinical site. “We are excited to be part of the study and look forward to enrolling patients into the clinical trial.”

 

TRIAL RESULTS

Second patient in Ph I trial achieves full remission from HPV-related head & neck cancer upon treatment with synthetic DNA vaccine, MEDI0457 followed by pembrolizumab


Dr. J. Joseph Kim, Inovio’s President and CEO, said, “Achieving sustained complete responses with immunotherapy in metastatic cancer patients is what you hope for with novel cancer treatments. The fact that the treatment with our synthetic DNA vaccine followed with two different PD-1 inhibitors in this HPV-related cancer patient population showed a complete response in 2 out of 4 progressors is very encouraging as the best complete response rate by PD-1 inhibitors as a monotherapy in metastatic head and neck cancer is approximately 4%. While additional data from Phase 2 clinical studies will provide more insights to the power of synthetic DNA vaccine, this newly reported data provides additional validation for Inovio’s overall cancer combination strategy using a T cell activator combined with a checkpoint inhibitor against an array of cancers with big pharma partners providing various checkpoint inhibitors. In addition to our partnership around HPV-related cancers, Inovio is also collaborating with F. Hoffman-La Roche Ltd./Genentech and Regeneron in efficacy trials coupling Inovio’s INO-5401 with their checkpoint inhibitors designed to increase response rates in metastatic bladder and GBM, respectively, with interim efficacy data expected later this year.”

 

FAILED TRIAL: Ph III RESOLVE trial of BTKi Ibrutinib failed to meet primary endpoint of PFS or OS benefit in 1L metastatic pancreatic cancer patients


“We continue to evaluate the potential of IMBRUVICA as a cancer treatment alone or in combination for a variety of cancer types. We are passionately advancing our robust ibrutinib scientific development program to continue to advance cancer standards of care, particularly in areas that have unmet medical need,” said Danelle James, M.D., M.A.S., Head of Clinical Science at Pharmacyclics LLC, an AbbVie company.

 

Data from Ph I/II trial of activated allogeneic dendritic cell therapy Ilixadencel +/- Sorafenib in HCC patients published


“With the broad potential of ilixadencel, it is important for us to gain insight on specific indications and treatment regimens. The clinical and biological information gathered through this trial has been invaluable to our understanding of safety, mechanism of action of ilixadencel and potential clinical activity in HCC, and we are pleased to have the results of the trial peer-reviewed and published in a well-reputed international scientific journal,” said Peter Suenaert, MD, PhD, Chief Medical Officer at Immunicum. “The safety profile of ilixadencel and the immune priming results corroborate our previously reported data and provide a firm foundation to continue exploring the potential of ilixadencel as part of combination treatment in liver cancer.”

 

Data from Ph III REACH-2 trial of Ramucirumab in 2L AFP-high HCC patients


“AFP has been used as a prognostic factor for hepatocellular carcinoma for decades. Some studies have suggested that AFP-producing tumors have an aggressive phenotype and increased angiogenesis,” said Andrew X. Zhu, M.D., Director of Liver Cancer Research at Massachusetts General Hospital Cancer Center, Professor of Medicine at Harvard Medical School, and principal investigator of the REACH-2 and REACH trials. “These results not only further add to the body of evidence that poor prognosis tumors with elevated AFP may have a distinct biology, but also show a tailored treatment approach is feasible.”

 

TRIAL STATUSES

First Mesothelioma patient dosed in Ph I trial of VISTA/PD-L1 dual inhibitor CA-170

“We are pleased to announce that the CA-170 study has begun dosing patients ahead of schedule,” said James Dentzer, President & CEO of Curis. “On last quarter’s earnings call, we outlined the reorganization of company resources to strengthen focus on clinical execution.  Today’s announcement is a result of those efforts. We re-iterate our confidence in our expectation to report initial efficacy data in this study in the second half of 2019.”


FDA puts partial clinical hold on Ph III AIM2CERV study of axalimogene filolisbac (AXAL) in high-risk, locally advanced cervical cancer


“FDA’s review of the AXAL Investigational New Drug (IND) application was prompted by our proposal to modify the AIM2CERV trial’s analysis plan to include, among other things, allowance for a second formal interim analysis for both safety and efficacy,” said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. “The primary focus of the items raised by the Agency relates to providing additional clarifying details for CMC information previously provided in support of Phase 3 development and which will help support a future Biologics License Application. We have already begun efforts to address the Agency’s requests for information and are working to respond as promptly as we can.” He concluded, “Our AXAL product has demonstrated a manageable safety profile in the over 400 patients we have dosed to date and we look forward to enrolling new patients in our AIM2CERV trial after FDA agrees that the information we submit is responsive to its requests.”

 

Ph Ib/II trial started for tubulin inhibitor VERU-111 in metastatic refractory prostate cancer patients

“Upon successful completion of this important clinical trial, we will move forward with additional clinical studies including a pivotal Phase 3 trial,” commented Mitchell Steiner, M.D., Chairman, President and Chief Executive Officer of Veru. “Based on earlier preclinical studies, VERU-111 should be effective against refractory prostate cancer and have a more favorable safety profile compared to intravenous taxanes. Drugs for advanced prostate cancer currently have over $3 billion in U.S. annual sales. Our preclinical studies also suggest that VERU-111 may be effective as a treatment for breast, ovarian, pancreatic and other prevalent cancers.”

 

COLLABORATIONS & ACQUISITIONS

Ph I/II trial testing FGFR inhibitor derazantinib and atezolizumab in FGFR+ urothelial cancer patients planned


Dr. Marc Engelhardt, Chief Medical Officer of Basilea, said: “We are very pleased with this collaboration. This is an important study as it explores a novel targeted treatment approach that addresses the high medical need of patients with urothelial cancer.” He added: “The combination of derazantinib and atezolizumab is based on a sound scientific rationale. In addition to its effects on FGFR kinases, derazantinib also inhibits the colony-stimulating factor-1-receptor kinase (CSF1R). CSF1R inhibition has the potential to enhance the response to atezolizumab’s immune-checkpoint inhibition. The combination of inhibiting FGFR while, at the same time, enhancing T cell-mediated antitumor effects through CSF1R inhibition is potentially a promising new treatment approach in patients with urothelial cancer.”

 

GlaxoSmithKline completes acquisition of TESARO


Dr Hal Barron, Chief Scientific Officer and President, R&D, GSK, said: “Both GSK and TESARO are driven by a focus on patients and a deep desire to develop truly transformational medicines that can improve and extend their lives. The acquisition of TESARO, which we have completed today, significantly strengthens our oncology pipeline and brings new scientific capabilities and expertise that will increase the pace and scale at which we can help patients living with cancer.”

 

UPDATED COVERAGE LIST FROM ASCO-GI 2019

  1. Preliminary data presented from Ph IIa trial of RX-3117 + Nab-Paclitaxel in 1L metastatic pancreatic cancer patients
  2. Positive data presented from Ph Ib/II trial of TRC105 + Sorafenib in HCC patients
  3. Data from Ph III TRYbeCA-1 trial of eryaspase in 2L pancreatic cancer patients presented
  4. Pembrolizumab reduces risk of death by 31% in PD-L1+ 2L esophageal/GEJ carcinoma pts in Ph III KEYNOTE-181 trial
  5. Five noteworthy studies in the treatment and management of liver, esophageal, colorectal, and colon cancers
  6. Updated data from Ph II trial of HER2 inhibitor Margetuximab + Pembrolizumab in gastric cancer patients to be presented
  7. Plan for Ph III AVENGER 500 trial of altered metabolism directed (AMD) drug devimistat (CPI-613) + mFOLFIRINOX in 1L pancreatic cancer patients to be presented
  8. Bayer to highlight new research
  9. Positive Varlitinib + chemotherapy data in 1L BTC patients from Ph Ib/II trial to be presented
  10. Post-hoc analyses data from Ph III REFLECT trial of Lenvatinib in HCC patients to be presented
  11. Encorafenib + Binimetinib + Cetuximab combination yields mOS of 15.3 months in BRAF mutated 2L-3L mCRC patients in Ph III BEACON CRC trial
  12. Ph III TAGS trial data of LONSURF® (trifluridine/tipiracil) in metastatic gastric cancer patients to be presented
  13. Data from Ph III INT-11 trial of CXCL12 inhibitor Tipifarnib in pancreatic cancer patients to be presented
  14. Data from safety lead-in to Ph III FIGHT trial of FGFR2b inhibitor Bemarituzumab presented
  15. Metabolic-based cancer therapy, SM-88, improves survival in Ph II trial of advanced Pancreatic Cancer patients

Cancer versus other causes of death in USA

 

(Source: https://seer.cancer.gov/statfacts/html/common.html)

 

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 Dey

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: “A polymorphic immune cell (red) glides over two spherical V12Ras-transformed mucus-secreting cells (green, possible tumor precursors) in a live three day old zebrafish embryo. This is one of four images in a series that illustrates the movement of the immune cell over the surface of the transformed mucus-secreting cells.” Source

The contents of Club SciWri are the copyright of PhD Career Support Group for STEM PhDs {A US Non-Profit 501(c)3}. (PhDCSG is an initiative of the alumni of the Indian Institute of Science, Bangalore. The primary aim of this group is to build a NETWORK among scientists, engineers and entrepreneurs).

This work by Club SciWri is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Disclaimer

The authors and editors for Onco-this-week declare no financial benefits or remuneration from the sponsors. The sponsorships support the non-profit organization PhD Career Support Group (PhD CSG). The research conducted by authors and editors is a voluntary effort to popularize science for the public on behalf of PhD CSG. The sponsors do not have any influence on the nature or kind of the news/analysis reported in Onco-this-Week. The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of Club SciWri or PhD CSG. Examples of analysis performed within this article are only examples. They should not be utilized in real-world analytic products as they are based only on very limited and dated open source information. Assumptions made within the analysis are not reflective of the position of anyone volunteering or working for Club SciWri or PhD CSG. This blog is strictly for news and information. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

SHARE THIS

The contents of Club SciWri are the copyright of Ph.D. Career Support Group for STEM PhDs (A US Non-Profit 501(c)3, PhDCSG is an initiative of the alumni of the Indian Institute of Science, Bangalore. The primary aim of this group is to build a NETWORK among scientists, engineers, and entrepreneurs).

This work by Club SciWri is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Tags

Related articles

Latest from Club SciWri