AACR ANNUAL MEETING 2018: MAJOR UPDATES
Editor’s note: As the world’s oldest and largest professional association related to cancer research, the American Association for Cancer Research (AACR) focuses on all aspects of cancer research, including basic, clinical, and translational research into the etiology, prevention, diagnosis, and treatment of cancer. Founded in 1907 by 11 physicians and scientists, the organization now has more than 34,000 members in over 90 countries. As the AACR held its Annual Meeting in Chicago, Richa Tewari was there to bring you the major updates from this meeting. Check out the educational YouTube video featuring Elaine Mardis (chair of AACR2018 Program Committee), as she summarizes the hot topics at this meeting and also get a taste of the 110 year-old history of AACR before we conclude this report.- Abhi Dey
Educational Video: Dr. Elaine Mardis, chair of this year’s AACR Program Committee, talks about the hot topics for AACR 2018, technological hurdles for bringing cancer research discoveries into medical practice, and the prospect of turning cancer into a chronic disease.
More than 20,000 Cancer Researchers Converge at International Meeting – #AACR18 https://t.co/GI2qbHL0yg via @pancan
— Raymond DuBois (@Rndubois) April 20, 2018
Dual Inhibition of IDO1 and PD-L1 safe in patients with advanced solid tumors as per ECHO-203 trial data
“Immune checkpoint inhibitors, including PD-1 and PD-L1 inhibitors, have provided meaningful clinical benefits for patients with cancer; however, novel immunotherapy combination treatments are needed to improve efficacy with limited additive toxicity,” said Aung Naing, MD, FACP, associate professor, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston. “This is the first report of IDO1 inhibition in combination with PD-L1 antagonism, and we found that epacadostat plus durvalumab was generally well-tolerated in patients with advanced cancers, with a safety profile consistent with previous reports of durvalumab monotherapy.”
RT Transplant_Doc “RT AACR: Next up: AnaingMD from MDAndersonNews presenting data from the ongoing ECHO-203 clinical trial. #AACR18 https://t.co/KdFVtIZzUk pic.twitter.com/6N9o1xxROJ“
— Robert Z. Orlowski (@Myeloma_Doc) April 17, 2018
Encouraging response rates observed with SD-101 + Pembrolizumab in advanced SCCHN patients
“Results from our Phase 1b/2 trial of SD-101 in combination with KEYTRUDA are promising in head and neck cancer, a condition for which patients typically have a poor prognosis,” said Eddie Gray, Chief Executive Officer of Dynavax. “This is another tumor type in which SD-101, based on early data, has demonstrated encouraging activity while being well tolerated. As understanding of combination therapy matures we believe an effective immune stimulating agonist with an attractive tolerability profile will play a significant role in a wide range of tumors.”
$DVAX Dynavax Is Flying! Strong Chart. Much activity in the April Calls expiring on the 20th. Two SD-101+ KEYTRUDA presentations at AACR (April 16-17): first results in head and neck cancer, durability of response data in melanoma. Excellent early results reported at ASCO 2017. pic.twitter.com/rGyPkgD3vY
— Solar Melt (@SolarMelt) March 28, 2018
Nivolumab demonstrated sustained OS advantage In CheckMate -141 trial over SoC in recurrent or mSCCHN patients
“The introduction of Immuno-Oncology has the potential to change the treatment landscape of squamous cell carcinoma of the head and neck, compared with the standard of care,” said Robert L. Ferris, M.D., Ph.D., a cancer immunotherapist and Director, UPMC Hillman Cancer Center, Pittsburgh, PA. “The sustained overall survival benefit demonstrated by nivolumab in this study is encouraging in SCCHN, which historically has a median survival of less than six months.”
“Opdivo is the only I-O treatment for squamous cell carcinoma of the head and neck to have shown a significant overall survival benefit versus chemotherapy at the primary analysis. These two-year follow-up data show a sustained long-term overall survival benefit for patients, across PD-L1 expression levels and regardless of HPV status,” said Shinta Cheng, M.D., Ph.D., development lead, Bristol-Myers Squibb. “These data showing the durability of this benefit reinforce our ongoing commitment to continuing research with the hope of delivering what matters most to patients fighting cancer: long-term survival.”
Head still spinning from the IO showdown at #AACR18? To keep track of the data, I have a comparison of the PFS and OS hazard ratios between the different trials. Note the data from CheckMate-227 is only from TMB-high patients $BMY $MRK $RHHBY pic.twitter.com/JHs0xOlL3v
— Matthew Maryniak (@drug_czar) April 16, 2018
Neoadjuvant Nivolumab showed safety and yielded pathologic responses in resectable NSCLC patients in Ph II trial
“The rationale for neoadjuvant anti-PD1 treatment of resectable NSCLC was essentially to use the primary tumor as a “vaccine” to induce T cells against the tumor antigens that would then circulate through the body systemically and seek out any distant sites of micrometastases,” said senior author of the study Drew Pardoll, MD, PhD, director of Bloomberg~Kimmel Institute for Cancer Immunotherapy and director of Cancer Immunology at Johns Hopkins School of Medicine. “Micrometastases are the primary source of relapse after surgery.”
Drew Pardoll on neoadjuvant #nivolumab in stage 1-3 #NSCLC from #AACR18. Watch the video: https://t.co/utWYjEVUkP pic.twitter.com/BXKqZxcXfV
— IC ImmunoOncology (@ic_immunoonco) April 17, 2018
Pembrolizumab reduced the risk for recurrence in stage 3 melanoma patients in Ph III KEYNOTE-054 trial
“Patients with stage 3 melanoma have metastatic disease in one or more regional lymph nodes,” said Alexander M. M. Eggermont, MD, PhD, director general of Gustave Roussy Cancer Campus Grand Paris in Villejuif, France. “A patient’s risk of recurrence depends on the number of lymph nodes affected and the tumor load. Those classified as having a high risk of recurrence have one or more regional lymph nodes with melanoma metastasis. In the case of a single positive node, the diameter must be greater than 1 millimeter.
“We were pleased to see that adjuvant pembrolizumab, given as a flat dose of 200 milligrams every three weeks after surgery for up to a year, which is 18 doses, significantly reduced the risk of recurrence for patients with high-risk stage 3 melanoma that has been completely resected,” continued Eggermont. “We hope that these data will lead to regulators in the United States and Europe approving pembrolizumab as a new treatment option for these patients.”
Alexander Eggermont presents the results of KEYNOTE-054 on #AACR18. Watch them here https://t.co/uTd10a0PYh pic.twitter.com/fYmRh5CBbl
— IC ImmunoOncology (@ic_immunoonco) April 16, 2018
RET inhibitor, BLU-667, showed significant durable disease control in Ph I ARROW trial of patients with lung and thyroid cancers patients with RET oncogene
“There is a critical un-met need for effective drugs against cancers that have the RET alteration, as there are no highly potent inhibitors currently approved specifically for these RET-driven cancers,” said Vivek Subbiah, M.D., Assistant professor of Investigational Cancer Therapeutics. “The current treatments for these cancers are limited to traditional chemotherapy and earlier generations of multiple kinase inhibitors. These options have had limited success with often considerable side effects that significantly impact the patient’s quality of life.”
“The data announced today reveal the broad clinical potential of BLU-667, a potent and highly selective RET inhibitor, and further demonstrate the power and reproducibility of Blueprint Medicines’ proprietary drug discovery platform,” said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. “We believe the safety, clinical activity and pharmacodynamic results from the dose escalation portion of the Phase 1 ARROW trial demonstrate compelling proof-of-concept for BLU-667. We are particularly encouraged by the consistency of these early BLU-667 data across multiple tumor types, RET alterations and prior lines of therapy. Based on these data, we are excited to rapidly advance the global expansion portion of the trial, which will further evaluate an optimized dose of BLU-667 across a broad patient population with a focus on durability of activity.”
Impressive study from @BlueprintMed released at #AACR2018. Of the patients who received BLU-667 who had RET-altered solid tumors, 84% experienced a tumor reduction, including those who had progressed on prior multi-kinase therapy and immunotherapy. https://t.co/8gkNnZAdyy pic.twitter.com/rodcab2cu6
— Laura Panjwani (@LauraPanj) April 17, 2018
Crizotinib yielded 100% DCR in ALK-positive inflammatory myofibroblastic tumor adult patients
“Inflammatory myofibroblastic tumors can cause significant functional disabilities, organ dysfunction, and death. Surgery, including amputations and other debilitating interventions, is the mainstay of treatment, but complete resection is often not possible because of the proximity of the tumors to vital organs,” said Schöffski. “Inflammatory myofibroblastic tumors are usually resistant to conventional chemotherapy and radiotherapy, so patients with unresectable or locally recurring disease have few treatment options.”
“The NCCN [National Comprehensive Cancer Network] began recommending the off-label use of crizotinib as a treatment for ALK-positive inflammatory myofibroblastic tumors a few years ago, after a single ALK-positive patient was reported to benefit,” said Schöffski. “Our data in predominantly adult patients with inflammatory myofibroblastic tumors, combined with recently published data for children with this disease, support this recommendation and suggest that crizotinib should be considered the standard-of-care for patients with ALK-positive inflammatory myofibroblastic tumor who cannot be treated with surgery.
“Our study highlights how identifying the genetic drivers of a rare type of cancer can be used to find a new precision medicine for patients who otherwise have few treatment options,” Schöffski added. “The inclusion in our trial of a group of patients with ALK-negative inflammatory myofibroblastic tumors provides valuable insight into the selectivity of crizotinib and our understanding of this rare disease, even if we cannot formally compare the outcomes for the ALK-positive and -negative groups.”
There were superior patient-reported outcomes for the next-generation tyrosine kinase inhibitor alectinib compared to the standard of care TKI inhibitor crizotinib for patients with ALK-positive #NSCLC according to these results: https://t.co/d19CuRUua9 #LungCancer ##ELCC18 pic.twitter.com/vo4w9VwPcC
— Targeted Oncology (@TargetedOnc) April 16, 2018
Frontline Pembrolizumab + Pemetrexed + Platinum Chemotherapy in Ph III KEYNOTE-189 trial reduced the risk of death by half compared with chemotherapy in advanced non-squamous NSCLC: study meets primary end-point of OS and PFS
“In this trial, KEYTRUDA in combination with pemetrexed and platinum chemotherapy, compared with chemotherapy alone, prolonged overall survival and progression-free survival in patients with advanced nonsquamous non-small cell lung cancer regardless of PD-L1 expression,” said Dr. Leena Gandhi, director of thoracic medical oncology at NYU Langone’s Perlmutter Cancer Center and lead author of The New England Journal of Medicine paper. “There is good scientific rationale for combining KEYTRUDA with pemetrexed and platinum chemotherapy, and these clinical data now suggest this combination as a new standard of care for the first-line treatment of these nonsquamous non-small cell lung cancer patients.”
“Our goal is to extend the lives of patients with lung cancer, and the unambiguous survival findings from KEYNOTE-189 showing the risk of death was reduced by half in the KEYTRUDA arm are important not only for patients but also for the medical community,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “The results of this trial have the potential to change the treatment paradigm for patients with nonsquamous non-small cell lung cancer in the first-line setting, including patients whose tumors are either PD-L1 negative or are untested.”
@DrRiyazShah describing the ‘landmark’ keynote 189 just published. New standard of care in 1st line non-squamous NSCLC PDL1 <50% champ+pembrolizumab. What to do in >50%?? Interesting discussion #lungcancer #LCSM Fantastic Nordic Lung Cancer Symposium pic.twitter.com/MTYeKrsJSd
— Matthew Evison (@MatthewEvison1) April 20, 2018
Frontline Nivolumab + low dose Ipilimumab combination reduces the risk of progression or death by 42% vs. chemotherapy in NSCLC patients with high TMB: study met co-primary endpoint of PFS
“CheckMate -227 is the first Phase 3 study to demonstrate the important clinical benefit of combining two immunotherapy agents to treat first-line NSCLC patients with high TMB,” said Matthew D. Hellmann, M.D., study investigator and medical oncologist at Memorial Sloan Kettering Cancer Center. “Results demonstrated that first-line nivolumab plus ipilimumab can provide frequent, deep and durable responses compared with chemotherapy in patients with NSCLC who have TMB ≥10 mut/Mb. The trial also supports the rationale for molecular testing to determine potential biomarkers in patients with lung cancer.”
“Lung cancer is a highly complex disease, defined by multiple subtypes, making it increasingly important to define a more precise treatment approach for this disease,” said Sabine Maier, development lead, thoracic cancers, Bristol-Myers Squibb. “We are excited to have advanced the science by establishing in this study that TMB was an important biomarker that predicted which first-line lung patients experienced a clinically meaningful progression-free survival benefit with a chemotherapy-sparing option, Opdivo plus low-dose Yervoy combination. These results are an example of our goal to understand each patient type through our leading translational research capabilities.”
#AACR18 Ph3 CheckMate227 – Nivolumabe+Ipilimumabe aumenta SLP na 1ªL Ca pulmão metastático com Alta Carga Mutacional, independente do PD-L1 https://t.co/9RfbipvaWt @NEJM @CarolinaKHaddad @rcarvalhoonco @FabioSchutz78 @camillayamada Mais sobre Ca pulmão em https://t.co/IK2npXq2KP pic.twitter.com/cq1m0gd7rf
— MOC Brasil (@MOCBrasil) April 18, 2018
Nivolumab becomes first PD-1 Inhibitor to demonstrate superior survival benefit vs. chemotherapy in previously treated Chinese NSCLC patients
Sabine Maier, M.D., development lead, thoracic cancers, Bristol-Myers Squibb, said, “Opdivo is the only PD-1 inhibitor to have demonstrated an overall survival benefit versus chemotherapy in three randomized Phase 3 lung cancer studies. The positive findings from CheckMate -078 are consistent with the landmark global studies CheckMate -017 and -057, which led to Opdivo becoming a standard of care in most of the world for previously treated squamous and non-squamous NSCLC, and represent our commitment to bring transformational medicines to patients worldwide.”
【Congratulation】Prof. Yilong Wu from Guangdong General Hospital -The first person of China on AACR!Checkmate-078 phase 3 confirms nivolumab as preferred therapy in Asian patients w/ previously treated NSCLC ,and the results published on Lancet oncology @AACR @TheLancetOncol pic.twitter.com/A92uCDamo2
— Oncologynews (@Oncologynewspro) April 17, 2018
Updated OS data presnted for olaparib from Ph III OlympiAD trial in gBRCA+ve HER2neg metastatic breast cancer patients
Sean Bohen, executive vice president, global medicines development and chief medical officer at AstraZeneca, said, “OlympiAD is the first Phase 3 trial to demonstrate disease control with a PARP inhibitor in gBRCA-mutated, HER2-negative metastatic breast cancer. While the trial was not powered to show overall survival compared to chemotherapy, the results are another encouraging factor in the use of LYNPARZA for this patient population.”
Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, “For patients and physicians, these results are meaningful in that they support the progression-free survival endpoint – which showed that patients treated with LYNPARZA gained seven months chemotherapy-free time – and reinforce the importance of identifying BRCA status to optimize metastatic breast cancer management.”
#ASCO17 Olympiad PFS results for AstraZeneca’s Lynparza vs chemo pic.twitter.com/IkvJjt5aT4
— Emily Hayes (@emilykatehayes) June 4, 2017
Indoximod well tolerated with minimal toxicity in pediatric Diffuse Intrinsic Pontine Glioma (DIPG) patients
“These early data, though from a small cohort of pediatric patients, demonstrate the potential of the indoximod plus radiochemotherapy combination without an increase in toxicity for these children,” said Dr. Theodore S. Johnson, M.D., Ph.D., Associate Professor of Pediatrics at Augusta University, lead investigator for the trial.
“These initial findings further support the potential for indoximod in combination with other agents,” said Charles J. Link, Jr., M.D., Chairman and Chief Executive Officer. “We look forward to working with our investigators toward gathering more data on the effects of indoximod on this deadly disease.”
Indoximod-based immunotherapy is showing promises in combination with radiation and chemotherapy in phase I clinical trial for DIPG in children #AACR18 pic.twitter.com/t7ViBXI41u
— Simona Fiorani (@FioraniSimo) April 15, 2018
Durable Mcl-1 suppression seen in patients with advanced cancers with CDK Inhibitor CYC065 in Ph I clinical trial
“Our findings show that CYC065 is effective in suppressing the cancer survival protein Mcl-1 in peripheral blood for at least 24 hours,” said Geoffrey Shapiro, MD, PhD, Director, Early Drug Development Center, Dana-Faber Cancer Institute and Professor of Medicine, Harvard Medical School, Boston, MA. “The durable target inhibition achieved at the recommended Phase 2 dose provides a rationale to further evaluate this novel agent in Mcl-1, MYC or cyclin E amplified tumors.”
“The clinical data support biomarker-driven clinical development of CYC065 in selected patient populations,” said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. “In addition, the durable suppression of the Mcl-1 survival protein presents an exciting opportunity to combine CYC065 with other agents targeting the apoptosis pathway, such as venetoclax. We will soon be starting a clinical study testing CYC065 in combination with venetoclax in patients with relapsed/refractory chronic lymphocytic leukemia.”
Phase 1 data backs Cyclacel’s plans for CDK2/9 inhibitor https://t.co/Fjdu6PXQnr
— David Schull (@davidschull) April 17, 2018
Preliminary data presented from Ph 1 GARNET trial of PD-L1 inhibitor TSR-042 in MSI-H endometrial cancer and NSCLC patients
“Preliminary results from GARNET presented today at AACR are the first clinical data from expansion cohorts for TSR-042, our anti-PD-1 antibody,” said Mary Lynne Hedley, Ph.D., President and COO of TESARO. “These results demonstrate the clinical activity of TSR-042 and support our unique patient-centric dosing regimen that includes dosing every 6 weeks. We expect to complete enrollment in the MSI-H endometrial cohort of the GARNET trial by the end of the year. A regulatory submission for TSR-042 is planned in 2019. The breadth of TESARO’s immuno-oncology portfolio, which also includes antibodies targeting TIM-3 and LAG-3, enables us to evaluate both monotherapy and novel combination approaches with a goal of providing transformative therapies for people living with cancer.”
$TSRO IO pipeline deserve more respect (pd1, tim3, lag3)
TSR-042 at #AACR18 : a darkhorse in anti-pd1 space $BMY $MRK … ? pic.twitter.com/EmkFPYe3zb— Caesar (@CaesarBiotech) April 9, 2018
TLR9 Agonist CMP-001 + Pembrolizumab combination demonstrates early efficacy in Anti-PD-1 resistant metastatic melanoma patients
“Checkpoint inhibition is quickly becoming a key tool for oncologists to treat cancer,” said Mohammed Milhem, MBBS, clinical professor of internal medicine at the University of Iowa, Iowa City. “However, there are many patients that either initially respond to checkpoint inhibition and then progress, or never respond to this therapy to begin with. Finding safe and effective therapies for these patients is critical.”
“Based on these preliminary findings, the combination of CMP-001 and pembrolizumab appears to have a manageable safety profile and meaningful clinical activity,” said Milhem. “Additional larger studies in this patient population will need to be conducted to further evaluate the clinical benefit, but if the current results are confirmed, it appears that this combination could offer a new treatment option for patients with advanced melanoma who are not responsive to pembrolizumab.”
Intratumoral TLR9 agonist CMP001 rescan reverse resistance to PD1 blockade in metastatic melanoma #AACR2018 pic.twitter.com/g9WwNB0qj2
— Filip Janku (@FilipJankuMD) April 17, 2018
From Visually.
Next time, See you in Atlanta!
It was a pleasure to meet each of you at @AACR, 2018. Thank you for placing your trust in us. Please feel free to write on bd@cbcc.global to discuss any queries. #AACR18 #ClinicalTrials #Oncology #MedicalDevices #CBCCGlobal #Cancer pic.twitter.com/12UMY6e1Wj
— CBCC Global Research (@cbcc_global) April 19, 2018
And before we sign-off, let’s relive the history of AACR from this YouTube Video
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: Multiphoton fluorescence image of HeLa cells stained with the actin binding toxin phalloidin (red), microtubules (cyan) and cell nuclei (blue). Nikon RTS2000MP custom laser scanning microscope. By National Institutes of Health (NIH) (National Institutes of Health (NIH)) [Public domain], via Wikimedia Commons
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