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Onco-this-Week

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HIGHLIGHTS

  1. Priority review to Ivosidenib’s sNDA in 1L IDH1m+ unfit AML patients. Not too earlier, in fact seven months to be precise, Ivosidenib had scored FDA approval in relapsed or refractory IDH1m+ AML patients. And the drug is already set to enter the frontline settings. The best part is that both the trials (R/R settings and 1L setting) are Ph I trials – explaining the grave unmet need in this patient population. The quick timelines, however, can be attributed to FDA’s Real-Time Oncology Review pilot program. PDUFA date is June 2019 and it would be great to welcome Ivosidenib in this population!
  2. Priority review to Pembrolizumab in 3L SCLC. What may come as a great hope to many, Pembrolizumab monotherapy was granted priority review in heavily pre-treated SCLC patients on the basis of data from SCLC cohorts of the Ph II KEYNOTE-158 and Ph Ib KEYNOTE-028 trials. After a series of failures in this patient segment with great unmet need, all the eyes would be Pembrolizumab as the PDUFA date of Jun 2019 gets closer. May it replicate the success of immunotherapies in NSCLC!
  3. Pembrolizumab’s failure in HCC. Not all was rosy for Merck and Pembrolizumab this week though – Ph III pivotal confirmatory KEYNOTE-240 trial of Pembrolizumab failed to meet primary endpoints of OS and PFS improvement. The shocker: the comparator arm was nothing but placebo in these previously-treated HCC patients. How would this negative data readout impact Pembrolizumab’s approval in 2L HCC patients and label, is yet to be seen.

This edition of Onco-this-Week is Sponsored by

North America Immigration Law Group & Nano-Tag Biotechnologies

 

DRUG APPROVALS

FDA approves Pembrolizumab in adjuvant melanoma based on data from Ph III EORTC1325 / KEYNOTE-054 trial

“In the fight against cancer, progress is made one step at a time, and today we’re pleased to take another important step – making KEYTRUDA available as an adjuvant therapy for patients with stage III melanoma,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “At Merck, we are committed to transforming the treatment of cancer, as is exemplified by this important advance in the adjuvant treatment of melanoma.”

 


REGULATORY NEWS

Priority review granted to Ivosidenib’s sNDA in 1L IDH1m+ AML patients not eligible for standard therapy; PDUFA: Jun 2019


“In less than seven months since TIBSOVO’s approval in relapsed or refractory AML, we are pleased to be working with the FDA to expand its labeled indication into the frontline setting,” said Chris Bowden, M.D., chief medical officer of Agios. “Patients with newly diagnosed AML who are not eligible for standard treatments, such as intensive and non-intensive chemotherapy, are currently offered only palliative care. There is tremendous need for new treatment options, and we believe AML patients with IDH1 mutations have the potential to benefit from this targeted therapy.”

 

Priority review granted to Pembrolizumab monotherapy in 3L SCLC on the basis of SCLC cohorts of the Ph II KEYNOTE-158 and Ph Ib KEYNOTE-028 trials; PDUFA: Jun 2019


“There is a significant need for new treatment options for small cell lung cancer, which has a five-year survival rate of only six percent overall,” said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. “KEYTRUDA has already been established as an important treatment option for many patients with advanced non-small cell lung cancer and this acceptance provides an opportunity to potentially benefit even more patients.”

 

Priority Review granted to Entrectinib in NTRKfusion-positive, locally advanced/metastatic solid tumors based on pivotal Ph II STARTRK-2, Ph I STARTRK-1 & ALKA-372-001 trials data; PDUFA: Aug 2019


“Entrectinib represents a unique approach to cancer treatment that can potentially target a range of hard-to-treat and rare NTRK fusion-positive tumours regardless of their site of origin, as well as treat ROS1-positive non-small cell lung cancer,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “By combining comprehensive genomic profiling with actionable targeted therapies, like entrectinib, we are advancing our personalised healthcare goal to find the right treatment for each patient. We are working closely with the FDA to make this potential new option available as soon as possible.”

 

Priority Review granted to CD79b-targeting ADC Polatuzumab vedotin in R/R DLBCL based on Ph Ib/II GO29365 study data; PDUFA: Aug 2019


“Polatuzumab vedotin, a potential first-in-class antibody drug conjugate, in combination with bendamustine and Rituxan, improved clinical outcomes including survival in some people with relapsed or refractory diffuse large B-cell lymphoma compared to bendamustine and Rituxan alone,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “We are working with the FDA to bring this important new option to patients with this aggressive disease as quickly as possible.”

 

FDA accepts IND application to initiate Ph I trial of Met-targeting PBD ADC, TR1801-ADC (MT-8633), in cMet +ve solid tumors


“We are excited to be able to move TR1801-ADC into the clinic,” said Roland Newman, TRL’s Chief Scientific Officer. “TR1801-ADC is an extremely potent ADC that combines a non-agonizing anti-c-Met antibody developed at TRL, with a pyrrolobenzodiazepine dimer (PBD) toxin, and has demonstrated potent dose dependent anti-tumor activity against Met positive tumors in preclinical models.”

 

Avapritinib receives Ph III clinical trial approval for 3L KIT-driven GIST in China after encuraging Ph I results in 4L+ GIST patients


Dr. Frank Jiang, chairman and CEO of CStone, commented: “Avapritinib is a first-in-class precision medicine drug that has been awarded Breakthrough Therapy Designation by the U.S. FDA due to its outstanding clinical efficacy. Current available clinical data already demonstrated the drug’s great potential for advanced GIST patients. CStone is delighted to be able to introduce this product to Chinese patients via our partnership with Blueprint Medicines, and we look forward to generating positive clinical data in China.”

 

TRIAL RESULTS

Ph III pivotal KEYNOTE-240 trial of Pembrolizumab fails to meet primary endpoints of OS and PFS improvement vs placebo in previously-treated HCC patients


“While we are disappointed KEYNOTE-240 did not meet its co-primary endpoints, the results for overall survival, progression-free survival and objective response rate are generally consistent with findings from the Phase 2 study, KEYNOTE-224, which led to the accelerated approval of KEYTRUDA for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We sincerely thank the patients and investigators for their participation in this study and are committed to helping patients diagnosed with this common and difficult-to-treat type of liver cancer.”

 

 

TRIAL STATUSES

First patient dosed in Ph Ib trial of B7-H4 inhibitor FPA150 in B7-H4-overexpressing patients with breast, ovarian, and endometrial tumors


“We are very pleased with the progress of our FPA150 clinical program that began with a dose escalation study in solid tumors and rapidly proceeded to an exploratory basket cohort of tumors that over-express B7-H4,” said Helen Collins, Senior Vice President and Chief Medical Officer. “We have now dosed the first patient in the Phase 1b dose expansion portion of the trial. FPA150 specifically targets B7-H4, which is in the same family of checkpoint inhibitors as PD-L1 and is over-expressed in breast and gynecological cancers that are not well served by immunotherapy. We are hopeful that a targeted immunotherapy like FPA150 will provide clinical benefit to these patients who have limited treatment options.”

 

Ph I trial of CD19-targeting PBD ADC, ADCT-402 (loncastuximab tesirine), and Ibrutinib initiated in advanced DLBCL and MCL patients


Jay Feingold, MD, PhD, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics, said, “At the 60th American Society of Hematology (ASH) Annual Meeting, the data we presented from our 183-patient first-in-human clinical trial of ADCT-402 demonstrated its encouraging safety profile and anti-tumor activity as a single agent against relapsed or refractory diffuse large B-cell lymphoma and mantle cell lymphoma. Now, in our second combination trial of ADCT-402, we look forward to exploring whether ADCT-402 and ibrutinib, both of which target B-cell cancers with different mechanisms of action, may increase the response rate and durability of response compared to the effects of these compounds as single agents.”

 

Ph II MAGNOLIA trial of BTK inhibitor Zanubrutinib initiated in R/R MZL patients


“We are excited to initiate this Phase 2 trial following the preliminary results from our Phase 1 trial of zanubrutinib in patients with relapsed or refractory marginal zone lymphoma, in which seven objective responses in nine patients were reported. More than 1,300 patients worldwide have been treated with zanubrutinib, and we look forward to evaluating its potential in the MAGNOLIA trial for these patients who may find benefit with this novel BTK inhibitor,” commented Jane Huang, M.D., Chief Medical Officer for Hematology at BeiGene.

 

FDA puts partial clinical hold on Ph I trial of anti-CD123 x anti-CD3 antibody XmAb14045 in R/R AML patients


Bassil Dahiyat, president and chief executive officer of Moravia, Calif.-based Xencor, said patient safety is the highest concern of the company. “We are working with the investigators and the FDA and will provide an update when more information about resuming enrollment can be shared. Our ongoing Phase 1 studies evaluating our other CD3 bispecific antibodies, XmAb13676 and XmAb18087, are not affected,” Dahiyat said in a statement.

 

Ph I/Ib trial of Deep-Primed T cell product TRQ-1501 initiated in Advanced Solid Tumors or Lymphoma patients


“We are grateful to the patients and clinical researchers contributing to Torque’s first Deep-Primed T Cell clinical program,” said Bart Henderson, Chief Executive Officer of Torque. “We developed Deep-Primed T cells to overcome the main challenges limiting cellular immunotherapy—the ability to target heterogenous tumors, overcome immunosuppression in the tumor microenvironment, and administration as outpatient therapy—and our hope is that this innovative treatment will shift the treatment paradigm, improving patient outcomes in multiple difficult-to-treat solid and hematologic cancers.”

 

COLLABORATIONS & LICENSING DEALS

Deep IL-15 Primed T Cells (TRQ-1501) to be tested both as a single agent and in combination with Pembrolizumab in Ph I/II study in multiple solid tumor indications


“We are very excited about this clinical collaboration with Merck to evaluate the combination of KEYTRUDA with our Deep IL-15 Primed T cells,” said Bart Henderson, Chief Executive Officer of Torque. “Torque’s new class of cellular immunotherapy is designed to harness the full biology of natural T cells for treating multiple solid tumors, and we believe the combination with anti-PD-1 therapy will further enhance the function of these cells by protecting them against immunosuppression in the tumor microenvironment. This combination has the potential to improve treatment outcomes for patients with solid tumors that are relapsed or refractory to currently available treatments and broaden the applications of cellular immunotherapy.”

 

RESULTS // ASCO GU 2019

  1. Results of discontinued Ph Ib/II trial of AKT oligonucleotide inhibitor RX-0201+ Everolimus in mRCC patients presented
  2. Updated interim data from Ph IIa trial of nucleic acid synthesis inhibitor RX-3117 in advanced bladder cancer patients presented
  3. Topline data from Ph III TIVO-3 trial of VEGF TKI Tivozanib in R/R RCC patients presented
  4. Data from Ph I/II PIVOT-02 trial of CD122-biased agonist NKTR-214 + nivolumab in 1L advanced/metastatic urothelial carcinoma patients presented
  5. Pembrolizumab + Axitinib extended OS and PFS in 1L RCC patients in Ph III KEYNOTE-426 trial
  6. Updated Ph I data of glutaminase inhibitor Telaglenastat + Cabozantinib in advanced RCC patients presented
  7. Subgroup analyses data announced and published from Ph III JAVELIN Renal 101 trial of Avelumab + Axitinib in advanced RCC patients
  8. Statistically significant improvement in MFS observed in Ph III ARAMIS trial of ARi Darolutamide in nmCRPC patients; mOS not reached
  9. Nivolumab + Ipilimumab show response in pre-treated mCRPC patients in Ph II CheckMate-650 trial
  10. Promising response rates observed in interim analysis of Ph II GALAHAD trial of Niraparib in mCRPC patients with DRD
  11. Encouraging SM-88 results observed without typical hormone-related AEs in Ph II trial of patients with biomarker recurrent Prostate Cancer
  12. Safety lead-in data presented from Ph II trial of PLK1 inh Onvansertib + abiraterone acetate/prednisone in mCRPC patients
  13. Trial design of Ph Ib/II trial of tubulin inhibitor VERU-111 in mCRPC patients presented
  14. Immunomedics presented trial design of Ph II TROPHY U-01 and longer follow-up data on TRPO2-targeting SN38 ADC sacituzumab govitecan in mUC patients from Ph I/II trial
  15. Merck highlighted clinical updates from KEYNOTE-199, -365, -057, -0426, -427 and PROPEL trials
  16. Data from Ph II CALYPSO trial of c-MET inh Savolitinib + Durvalumab in papillary RCC patients presented
  17. LuPSMA treatment provides high response rates in mCRPC patients
  18. Pembrolizumab + Axitinib extended OS and PFS in 1L RCC patients in Ph III KEYNOTE-426 trial
  19. Ph III ARCHES trial shows enzalutamide significantly improved radiographic PFS in mCSPC patients
  20. Results from Ph II trial of FGFR3 inh Vofatamab in FGFR3 mutation positive patients with locally advanced or metastatic bladder cancer presented

 

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. Currently, he is a Lead Scientist at MicroCures Inc. Previously, he served as 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 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: “Human melanoma cell undergoing cell division. The chromosomes (blue) have separated and the two daughter cells have almost split apart – only a small bridge of cytoplasm remains. The green staining labels the endoplasmic reticulum and the red labels the mitochondria. The image was produced on a confocal microscope; the ER and mitochondria are from a single optical section but the chromosomes are a 3D reconstruction from a series of sections.” Source

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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.

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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.

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