News Digest for April 2019

Posted on: 2019-04-20 15:39:25

April 1, 2019

The combination of savolitinib and osimertinib showed promising clinical activity among patients with EGFR-mutated non-small cell lung cancer resistant to prior EGFR-targeted therapies through MET amplification, according to interim results from two expansion cohorts of the TATTON trial presented at American Association for Cancer Research Annual Meeting.  MET amplification is the second most common driver of acquired resistance to EGFR tyrosine kinase inhibitors — after EGFR T790M — occurring in 5% to 30% of patients with resistance across case series.  (here)

April 3, 2019

OSE Immunotherapeutics today announced that new clinical and preclinical data on its products in immuno-oncology, Tedopi® and BI 765063 (OSE-172), were presented at the American Association of Cancer Research (AACR) Annual Meeting, held March 29-April 3, 2019 in Atlanta. (here)

Differential effects of adjuvant EGFR tyrosine kinase inhibitors in patients with different stages of non-small-cell lung cancer after radical resection: an updated meta-analysis.  (here)

BerGenBio Extends Phase II Trial With Bemcentinib and KEYTRUDA® in NSCLC to Include Patients With Disease Progression on Immune Checkpoint Inhibitor Therapy (here)

Resolution Liquid Biopsy Assay Outperforms Guardant360 in Retrospective Non-Small Cell Lung Carcinoma Comparison Pilot Study (here)

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Iovance Biotherapeutics, a late-stage biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, today announced an update to its clinical programs with TIL therapy in the treatment of cervical cancer and non-small cell lung cancer (NSCLC).  (here)

Dynavax:  Using an investigational safety treatment regimen, inhaled DV281 in combination with systemic nivolumab was well tolerated in a population of heavily pre-treated NSCLC patients -- Target engagement was observed at all dose levels -- Evidence of anti-tumor effects was seen at all dose levels  (here)

Bristol-Myers Squibb Announces Long-Term Survival Results from Pooled Analyses of Opdivo (nivolumab) in Previously-Treated Non-Small Cell Lung Cancer Patients  (here)

April 4, 2019

 

Next week, researchers from around the globe will gather in Geneva, Switzerland, for the 2019 European Lung Cancer Congress. During the meeting, multiple research teams will discuss new findings from research into the use of bevacizumab—which now has approved biosimilars that promise cost savings and expanded patient access—in nonsquamous non–small-cell lung cancer (NSCLC). (here)

Epigenetic therapies may help push solid tumors to be more responsive to other forms of treatment, according to speakers at this year's American Association for Cancer Research meeting here.  While there are no approved epigenetic therapies for solid tumors in the US, there are about half-a-dozen that are approved for use in hematological cancers and they have been under investigation for solid tumors like colorectal, lung, and breast cancers. Though studies of epigenetic therapies on their own for these tumor types have largely been disappointing, the speakers noted that there have been hints that epigenetic therapies could be used to prime these solid tumors to better respond to other types of therapies. (here)

Dr. Rizvi:  As investigators elucidate the role of tumor mutational burden (TMB) in cancer therapy, it is becoming clearer for which therapies it can serve as a stand-alone biomarker and where it needs to be looked at in relation to other disease characteristics and mutations.  (here)

Chi-Med CEO: New NSCLC Data Boosts Prospects For cMET Inhibitor Savolitinib (here)

 

The correlations of tumor mutational burden among single-region tissue, multi-region tissues and blood in non-small cell lung cancer (here)

April 6, 2019

High-dose stereotactic body radiotherapy well-tolerated by patients with centrally located lung tumors (here)

Third-line chemotherapy for NSCLC confers clinically meaningful PFS to immunotherapy-exposed patients (here)

 In the battle against non-small cell lung cancer, the ability to personalize treatment may be a key to victory, according to Karen Reckamp, MD, co-director of the lung cancer and thoracic oncology program at City of Hope.  Reckamp is the lead investigator of a phase 1 clinical trial examining a novel T-cell therapy for the treatment of NSCLC, the details of which she presented at American Association for Cancer Research Annual Meeting.  (here)

Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy (here)

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Big data enters the fray in the war against cancer as pharmaceutical laboratories combine drugs like cocktails to kill cancerous cells.  Drug cocktails are effective in suppressing HIV/Aids, and combination therapy is increasingly being applied to the battle front in the war on cancer.  Pharmaceutical companies are using big data analysis and machine learning to identify the most appropriate mix out of millions of possible drug combinations.  (here)

Less frequent dosing of first-line NSCLC therapy found to be safe and effective. // For patients with advanced non-small cell lung cancer (NSCLC), dosing with nivolumab every 4 weeks (Q4W) instead of every 2 weeks (Q2W) is as effective and safe as second-line therapy, according to results from an interim analysis of the phase 3b/4 CheckMate 384 study, presented at the 2019 American Society of Clinical Oncology–Society for Immunotherapy of Cancer (ASCO–SITC) Clinical Immuno-Oncology Symposium, held in San Francisco, CA. (here)

Gene testing is still very important to determine targeted therapies for patients with lung cancer despite the widespread use of immunotherapy, according to a presenter at Community Oncology Alliance Conference.  When deciding a treatment regimen for patients with lung cancer, it’s important to remember that immunotherapy alone may not be enough for some patients, the presenter added. (here)

April 8, 2019

Genprex, a clinical-stage gene therapy company, reported that its collaborators from MD Anderson presented positive preclinical data for the combination of the TUSC2 gene with an anti-PD1 antibody, pembrolizumab, for the treatment of lung cancer in a poster presented at the American Association of Cancer Research Meeting 2019. The TUSC2 gene is a tumor suppressor gene, the active agent in Genprex’s Oncoprex™ immunogene therapy. (here)

Researchers found that some cancer cells have been developing their own miniature stomach, duodenum and small intestine — an indication of plasticity of cells that could lead to tumors being drug-resistant. Their study was published in the journal of Developmental Cell. // "Cancer cells will do whatever it takes to survive," Purushothama Rao Tata, lead study author and assistant professor of cell biology at Duke University School of Medicine, said. "Upon treatment with chemotherapy, lung cells shut down some of the key cell regulators and pick up the characteristics of other cells in order to gain resistance." (here)

Relapse of disease following conventional treatments remains one of the central problems in cancer management, yet few therapeutic agents targeting drug resistance and tolerance exist. New research conducted at the Cancer Center at Beth Israel Deaconess Medical Center found that a microRNA—a small fragment of non-coding genetic material that regulates gene expression—mediates drug tolerance in lung cancers with a specific mutation. The findings, published today in Nature Metabolism, suggest that the microRNA could serve as a potential target for reversing and preventing drug tolerance in a subset of non-small-cell lung cancers. (here)

New data from clinical trials that led to the approval of immunotherapy with nivolumab (Opdivo, Bristol-Myers Squibb) in nonsmall cell lung cancer (NSCLC) now show that patients who respond to the drug have better survival in the longer term.  More than half (58%) of such patients were still alive after 4 years, whereas the historical survival of patients with advanced NSCLC has been 5% at 5 years. (here)   

Neon Therapeutics, a clinical-stage immuno-oncology company developing neoantigen-based therapeutics, today announced the completion of enrollment in NT-002, its Phase 1b clinical trial evaluating NEO-PV-01 with KEYTRUDA® (pembrolizumab) and chemotherapy in patients with untreated advanced or metastatic non-small cell lung cancer (NSCLC). NEO-PV-01 is a personal neoantigen vaccine custom-designed and manufactured based on the neoantigens identified by Neon’s proprietary bioinformatics engine, RECON®, as being the most therapeutically relevant for an individual patient. (here)

miRNA-99b-5p targets FZD8 to inhibit non-small cell lung cancer proliferation, migration and invasion (here)

April 9, 2019

A study from the University of Southern California, Keck School of Medicine, sought to examine possible health disparities in the treatment of lung cancer within the Asian community in the U.S. In this study, rates of recommended care for non-small cell lung cancer were compared among patients in the Asian community. The authors concluded that practice patterns within different Asian ethnicities vary widely, and cultural and gender preferences appear to exist for different modalities of care. (here)

Delivering an inhaled Dry Powder formulation of Aspirin directly into the deep sites of the lung is a novel new approach to lung cancer treatment. This new treatment can potentially provide benefits superior to other common therapies greatly improving clinical outcomes for patients being treated for lung cancer. (here)

Chul Kim, MD, MPH, an attending physician at MedStar Health and an assistant professor of medicine at Georgetown University, discusses overcoming mechanisms of resistance to TKIs in non–small cell lung cancer (NSCLC). (here)

Presented in a case report published in the Journal of Oncology Practice is a patient with unresectable, nonmetastatic non-small cell lung cancer (NSCLC) who developed apparent immunotherapy-induced hyperprogressive disease, involving development of distant metastases, shortly following consolidation therapy with a programmed cell death-ligand 1 (PD-L1) inhibitor administered after definitive chemoradiation therapy. (here)

Relapse of disease following conventional treatments remains one of the central problems in cancer management, yet few therapeutic agents targeting drug resistance and tolerance exist. New research conducted at the Cancer Center at Beth Israel Deaconess Medical Center found that a microRNA - a small fragment of non-coding genetic material that regulates gene expression - mediates drug tolerance in lung cancers with a specific mutation. The findings, published today in Nature Metabolism, suggest that the microRNA could serve as a potential target for reversing and preventing drug tolerance in a subset of non-small-cell lung cancers. (here)

Flat-Dose Nivolumab + Weight-Based Low-Dose Ipilimumab Is a Safe and Effective Alternative to Weight-Based Dosing as First-Line Treatment of NSCLC (here)

Marshall University researchers found that capsaicin hindered cell invasion, which precedes metastasis, in cultured non-small cell lung cancer cells, while mice with metastatic lung cancer that were given capsaicin had reduced metastatic lung cancer cell areas, compared with those that weren't given capsaicin.  (here)

April 11, 2019

Nicolas Guibert, MD, PhD, of Toulouse University Hospital, discusses a simple algorithm built to predict durable outcomes of patients with advanced non–small cell lung cancer that has been treated with immunotherapy. He notes that early changes in circulating tumor DNA burden may also predict sustained responses to PD-1 inhibitors.  (here)

Sodium new houttuyfonate suppresses metastasis in NSCLC cells through the Linc00668/miR-147a/slug axis (here)

Quick Take: Pembrolizumab Versus Chemotherapy for Previously Untreated, PD-L1-Expressing, Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (KEYNOTE-042) (here)

April 12, 2019 

FameWave Ltd. a privately held biopharmaceutical company developing CM-24, which is being acquired by Kitov Pharma, today announced the signing of a clinical collaboration with Bristol Myers Squibb Company (NYSE:BMY) to evaluate the combination of CM-24, FameWave’s monoclonal antibody targeting the novel immune checkpoint carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), with nivolumab (Opdivo®), a PD-1 inhibitor, in patients with non-small cell lung cancer (NSCLC). (here)

A team of researchers from the Dana-Farber Cancer Institute (MA, USA) has discovered the mechanism behind how thalidomide caused damage to developing fetuses. The discovery puts scientific curiosity to rest, for now, and provides crucial information for drug developers hoping to utilize the same molecular foundation in new cancer treatments. (here)

April 13, 2019

Early results from the ATALANTE-1 Phase 3 trial indicate that Tedopi benefits people with advanced non-small cell lung cancer (NSCLC) who failed to respond to prior checkpoint inhibitor therapy, OSE Immunotherapeutics reported.  Three enrolled patients responded positively to third-line treatment with Tedopi, either achieving a partial reduction of their tumors or experiencing stable disease, with a good safety profile.  (here)

Martin Reck, MD, Lung Clinic Grosshansdorf, discusses the rationale for the IMpower150 study, which assessed the combination of atezolizumab (Tecentriq), bevacizumab (Avastin), and chemotherapy in the first-line treatment of patients with nonsquamous non–small-cell lung cancer (NSCLC).  This trial was unique, explains Reck, in that it investigated a unique combination comprised of a checkpoint inhibitor, chemotherapy, and an antiangiogenic compound on the basis of the idea that the antiangiogenic compound combined with a checkpoint inhibitor could enhance the efficacy of immunotherapy. (here)

The encouraging activity with osimertinib (Tagrisso) for patients with EGFR-mutant non–small cell lung cancer (NSCLC) continues to be highlighted in the form of prolonged progression-free survival (PFS); however, next steps are focusing on understanding the primary and acquired resistance mechanisms to the third-generation EGFR inhibitor. (here and here

April 15, 2019

 

Immunogenic cell death (ICD) converts dying cancer cells into a therapeutic vaccine and stimulates antitumor immune responses. Here we unravel the results of an unbiased screen identifying high-dose (10 µM) crizotinib as an ICD-inducing tyrosine kinase inhibitor that has exceptional antineoplastic activity when combined with non-ICD inducing chemotherapeutics like cisplatin. The combination of cisplatin and high-dose crizotinib induces ICD in non-small cell lung carcinoma (NSCLC) cells and effectively controls the growth of distinct (transplantable, carcinogen- or oncogene induced) orthotopic NSCLC models. These anticancer effects are linked to increased T lymphocyte infiltration and are abolished by T cell depletion or interferon-γ neutralization. Crizotinib plus cisplatin leads to an increase in the expression of PD-1 and PD-L1 in tumors, coupled to a strong sensitization of NSCLC to immunotherapy with PD-1 antibodies. Hence, a sequential combination treatment consisting in conventional chemotherapy together with crizotinib, followed by immune checkpoint blockade may be active against NSCLC.  (here)

Niels Reinmuth, MD, Asklepios Lung Clinic, discusses the results of the phase III MYSTIC study, which evaluated the efficacy and safety of first-line durvalumab (Imfinzi) plus tremelimumab versus platinum-based chemotherapy in patients with metastatic non–small cell lung cancer.  Overall survival was analyzed in subgroups based on baseline clinical characteristics. Unfortunately, there was no single clinical characteristic identified. Although durvalumab was effective across all subgroups, it was not found to be statistically significant. This was predetermined, says Reinmuth, because there were 3 primary endpoints.  However, it appears that subsequent immunotherapy might have impaired the overall survival (OS) benefit of durvalumab in the first-line. About two-thirds of patients crossed over to receive a form of immunotherapy, although durvalumab was not permitted as a cross-over option. If statistical methods are applied, it appears that this subsequent immunotherapy may have led to improved outcomes in the chemotherapy-treated group.  (here)

James Chih-Hsin Yang, MD, National Taiwan University Hospital, discusses the final safety and efficacy results from 2 phase I expansion cohorts from the phase I/II AURA trial (NCT01802632). Both cohorts received osimertinib (Tagrisso) at a dose of either 80 mg or 160 mg for advanced EGFR mutation-positive advanced non–small cell lung cancer (NSCLC).  Results showed that the response rate has been high for both groups, at 67% and 87% for the 80-mg cohort and the 160-mg cohort, respectively. The median duration of response is approximately 20 months, which Yang explained is consistent with findings from the phase III FLAURA trial.  (here)

Results from a final analysis of the phase III KEYNOTE-042 trial have confirmed the benefit of pembrolizumab (Keytruda) monotherapy in patients with non–small cell lung cancer (NSCLC), said Tony Mok, MD. Results from the trial showed that frontline pembrolizumab demonstrated a median overall survival (OS) of 16.7 months versus just 12.1 months with standard chemotherapy in those with advanced or metastatic disease and a TPS ≥1%.2 Further, data from an exploratory analysis, which examined all patients with PD-L1 TPS of 1% to 49%, showed a median OS was 13.4 months with pembrolizumab compared with 12.1 months with chemotherapy. (here)

 

Dr. Reck:  Atezolizumab (Tecentriq) plus bevacizumab (Avastin), carboplatin, and paclitaxel (ABCP) has emerged as a potential new standard of care for patients with EGFR-positive metastatic nonsquamous non–small cell lung cancer (NSCLC) who have failed on TKI treatment, according to an exploratory analysis from the phase III IMpower150 trial presented at the 2019 European Lung Cancer Congress (ELCC). (here)

April 16, 2019

Current cancer therapies are often associated with treatment failure and reduced patients’ survival due to drug resistance. There are various mechanisms involved in the acquisition of cancer drug resistance, including the selection of advantageous mutations, overexpression of transporter proteins and epigenetic alterations. In this context, epigenetic alterations refer to chromatin-mediated regulation of gene expression that results in heritable changes in the cellular phenotype. There is an ever-growing body of evidence suggesting that epigenetic mechanisms play an important role in bringing about drug resistance in cancer cells. // This review discusses the involvement of histone lysine demethylases in the development of resistance to TKI and highlights the importance to develop new cancer treatment regimens to counteract this phenomenon. (here)

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Given that a wide range of changes in tumor size is included in a partial response, according to the Response Evaluation Criteria in Solid Tumors, researchers investigated if further specification of tumor reduction according to depth of response (DpR) would afford a more exact relation to outcomes for patients with non–small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy. Participants were NSCLC patients who have received carboplatin in combination with nab-paclitaxel or solvent-based paclitaxel. These subjects were retrospectively analyzed. The link between DpR and overall survival (OS) was primarily assessed. Findings revealed a strong association of DpR with OS in this study sample.  (here)

Mark A. Socinski, MD, AdventHealth, discusses new applications for immunotherapy in the treatment of patients with non–small cell lung cancer (NSCLC).  In order to capitalize on recent advances in the field, there are 2 basic elements that providers have to get right, explains Socinski. One is the diagnosis, which includes histology and PD-L1 status, or molecular status in stage IV disease. The second important factor is disease stage. // Most of the advancements with targeted therapy and immunotherapy have been in stage IV NSCLC, but the results of the PACIFIC trial are a huge step forward in the field. In that study, treatment with durvalumab (Imfinzi) following chemoradiation led to a median progression-free survival of 17.2 months compared with 5.6 months with placebo. Moreover, there are a number of adjuvant trials looking at immunotherapy and targeted therapies. (here)

Guardant Health announced that the positive results from the NILE study, a head-to-head comparison of the Guardant360® assay to standard-of-care tissue testing for the identification of guideline-recommended biomarkers in first-line advanced non-small cell lung cancer (NSCLC) patients, have been published in Clinical Cancer Research (here

April 17th, 2019

'Magic Mouthwash' Little Help for Radiation-Induced Mucositis.  Only statistical improvements in pain scores for head and neck cancer patients. // Two medicated mouthwashes led to reductions in oral mucositis pain for head and neck cancer patients treated with radiotherapy, but not at a level deemed clinically important, a randomized phase III study found. (here)

 

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New Approaches to Treating Drug-resistant Non-small Cell Lung Cancer // “To date, targeted therapy for lung cancer patients with EGFR mutations has consisted solely of monotherapy with various EGFR tyrosine kinase inhibitors, though we have known for more than 10 years that a proportion of resistance to EGFR TKIs results from activation of the MET bypass pathway,” said presenter Lecia V. Sequist, MD, MPH, from Massachusetts General Hospital Cancer Center, in a press release. (here)

A team from China, the US, and Malaysia has profiled the mutation patterns and tumor microenvironment features found in non-small cell lung cancer (NSCLC) cases treated at half a dozen hospitals in China. (here)

April 18, 2019

The epithelial to mesenchymal transition (EMT) is pivotal for driving metastasis and recurrence in lung cancer. Some in vitro reports have shown that statins suppress EMT by inactivating mutant p53 functions. Several clinical trials of conventional treatments with statins have been performed, but the effect of these drugs on prognosis is still uncertain. The purpose of this study is to examine the impact of statins on EMT and the prognosis of patients with lung adenocarcinoma. // Statins suppress EMT and change the prognosis of patients with lung adenocarcinoma in a p53 mutation-dependent manner. (here)

SK Biopharmaceuticals has collaborated with an artificial intelligence (AI)-driven biopharmaceutical firm twoXAR for the discovery and development of first-in-class treatments for non-small cell lung cancer (NSCLC). (here)

The FDA has expanded the approval of the PD-L1 IHC 22C3 pharmDX assay, allowing the test to be used as a companion diagnostic to identify more patients with stage III or metastatic non–small cell lung cancer (NSCLC) who can undergo first-line treatment with pembrolizumab (Keytruda). (here

April 20, 2019

University of Texas at Dallas scientists have demonstrated that the growth rate of the majority of lung cancer cells relates directly to the availability of a crucial oxygen-metabolizing molecule.  In a preclinical study, recently published in Cancer Research, biologist Dr. Li Zhang and her team showed that the expansion of lung tumors in mice slowed when access to heme — the oxygen-binding molecule in hemoglobin — was restricted. The researchers also showed that those same cancers grew faster when more heme was available than normal.  With an eye toward exploiting the cancer’s heme dependency, two of Zhang’s graduate students in the Department of Biological Sciences then engineered and extensively characterized new molecules aimed at starving the cancer cells of the molecule that allows them to proliferate so quickly.  (here)

 

 

April 22, 2019

Gritstone Oncology Announces Clinical Acceleration of “Off-The-Shelf” Personalized Neoantigen Immunotherapy Program (SLATE) Following FDA Feedback (here)

A deep-learning model developed using serial image scans of tumors from patients with non-small cell lung cancer (NSCLC) predicted treatment response and survival outcomes better than standard clinical parameters. (here)

April 24, 2019

Kartik Konduri, MD, Sammons Cancer Center, discusses treatment options available for patients with EGFR-mutant non–small cell lung cancer (NSCLC).  Data are eagerly anticipated from the phase III RELAY trial, in which investigators are examining the combination of erlotinib (Tarceva) and the antiangiogenic agent ramucirumab (Cyramza) in the frontline setting for patients with EGFR-mutant NSCLC. The trial was initially reported to be positive, but the full data set has yet to be released. (here)

The prognostic value of serum albumin–globulin ratio in early-stage non-small cell lung cancer: a retrospective study (here)

Knockdown of CHPF suppresses cell progression of non-small-cell lung cancer (here)

April 25, 2019

Poziotinib Data in EGFR Exon 20-Mutant NSCLC.  Insights From: John Heymach, MD, PhD, MD Anderson Cancer Center (here)

April 26, 2019

Recent advances in the field of novel anticancer agents prolong patients’ survival and show a promising future. Tyrosine kinase inhibitors and immunotherapy for lung cancer are the two major areas undergoing rapid development. Although increasing novel anticancer agents were innovated, how to translate and optimize these novel agents into clinical practice remains to be explored. Besides, toxicities and availability of these drugs in specific regions should also be considered during clinical determination. Herein, we summarize emerging agents including tyrosine kinase inhibitors, checkpoint inhibitors, and other potential immunotherapy such as chimeric antigen receptor T cell for non-small cell lung cancer attempting to provide insights and perspectives of the future in anticancer treatment.  (here)

lncRNA BANCR suppresses cell viability and invasion and promotes apoptosis in non-small-cell lung cancer cells in vitro and in vivo (here)

Niels Reinmuth, MD, Asklepios Lung Clinic, discusses ongoing studies looking at resistance to EGFR TKIs in patients with EGFR-positive non–small cell lung cancer (NSCLC).  There are a number of ongoing trials with osimertinib (Tagrisso) in which researchers are collecting tissue samples and performing liquid biopsies at the time of diagnosis and at the time of disease progression. Reinmuth says the field is eagerly awaiting the results of the studies as they could provide insight into mechanisms of resistance. There are also similar studies looking at other EGFR TKIs like dacomitinib (Vizimpro) that may give researchers a better idea of the biology driving response and acquired resistance. (here)

Tony S. K. Mok, Hong Kong, discusses updated data with pembrolizumab (Keytruda) in patients with non–small cell lung cancer (NSCLC). (here)

Chemoimmunotherapy has emerged as the frontline standard of care in patients with squamous non–small cell lung cancer (NSCLC), but work still needs to be done by way of determining effective biomarkers and identifying other effective combinations, said Eric S. Nadler, MD. (here)