Author Interviews / 15.06.2020

MedicalResearch.com Interview with: Nicholas J. Vogelzang, MD, FASCO, FACP Medical Oncologist at Comprehensive Cancer Centers of Nevada Associate Chair, US Oncology Research Genitourinary Committee MedicalResearch.com: What is the background for this study? Response: According to the American Cancer Society, prostate cancer is the second leading cause of cancer death in men in the U.S. New approaches are needed to target the androgen receptor (AR), a critical driver of metastatic castration resistant prostate cancer (mCRPC). Current agents work by decreasing androgen levels (abiraterone) or blocking androgen binding to AR (enzalutamide). Despite rapid and dramatic responses to standards of care, all patients with metastatic disease progress to the castration resistant state and their tumors continue to be dependent on the AR signaling axis.1 Study design:
  • “3 + 3” dose escalation; starting dose = 35 mg, orally, once daily with food
  • Dose increases dependent on toxicities
    • Range 25% to 100% based on severity of AEs
Inclusion criteria:
  • Men with mCRPC, regardless of AR status
  • At least two prior systemic therapies, at least one of which was abiraterone or enzalutamide
  • Disease progression on most recent therapy
    • Rising PSA or 2+ new lesions upon bone scan
Endpoints:
  • Primary:
    • Define the maximum tolerated dose and recommended phase 2 dose
  • Secondary:
    • Pharmacokinetics
    • Anti‐tumor activity (PSA50, RECIST criteria)
  • Exploratory:
    • Biomarkers
      • ctDNA mutational profiling
      • AR levels in optional paired biopsies
      • AR and AR‐ V7 levels in circulating tumor cells (CTCs)
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ASCO, AstraZeneca, Author Interviews, Cancer Research, Melanoma / 13.06.2020

MedicalResearch.com Interview with: Yuanbin Chen, MD, PhD Cancer & Hematology Centers of Western Michigan MedicalResearch.com: What is the background for this study? What are the main findings?
    • Response: The CASPIAN trial was a randomized, open-label, multi-center global Phase III trial in the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). The trial compared IMFINZI in combination with etoposide and either carboplatin or cisplatin chemotherapy, or IMFINZI and chemotherapy with the addition of a second immunotherapy, tremelimumab, versus chemotherapy alone – the primary endpoint being overall survival (OS). After a median follow up of more than two years, the latest results for IMFINZI plus chemotherapy demonstrate a sustained and clinically meaningful OS benefit for patients with extensive-stage small cell lung cancer (ES-SCLC), maintaining a 25% reduction in the risk of death versus chemotherapy alone. Updated median OS was 12.9 months versus 10.5 for chemotherapy.
      • In a post-hoc analysis, 22.2% of patients treated with IMFINZI plus chemotherapy remained alive after 24 months, versus 14.4%, for chemotherapy alone.
      • Post-hoc analysis also showed that for IMFINZI plus chemotherapy, 11.0% of patients were alive and progression-free at 24 months versus 2.9% for chemotherapy alone.
      • IMFINZI plus chemotherapy maintained a high confirmed objective response rate (ORR) (68% versus 58%) and in a post-hoc analysis, duration of response (DoR) for IMFINZI at 24 months was 13.5% versus 3.9% for chemotherapy alone.
      • At 24 months, 12% of patients in the IMFINZI plus chemotherapy arm remained on IMFINZI treatment.]
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ASCO, AstraZeneca, Author Interviews, Cancer Research, Lung Cancer, Yale / 13.06.2020

MedicalResearch.com Interview with: Roy S. Herbst, MD, PhD Ensign Professor of Medicine (Medical Oncology) Professor of Pharmacology Chief of Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital; Associate Cancer Center Director for Translational Research Yale Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings?
  • ADAURA is the first global trial for an EGFR tyrosine kinase inhibitor to show statistically significant and clinically meaningful benefit in adjuvant treatment of Stage IB, II, and IIIA EGFRm NSCLC. The results demonstrated unprecedented disease free survival (DFS) in the adjuvant treatment of these patients after complete tumor resection with curative intent. Osimertinib was assessed against placebo for a treatment duration of up to three years and then unblinded two years earlier than expected at the recommendation of the Independent Data Monitoring Committee (IDMC), based on its determination of overwhelming efficacy during a planned safety analysis.
  • In the primary endpoint of DFS in patients with Stage II and IIIA disease, adjuvant (after surgery) treatment with osimertinib reduced the risk of disease recurrence or death by 83% (based on a hazard ratio [HR] of 0.17; 95% confidence interval [CI] 0.12, 0.23; p<0.0001).
  • DFS results in the overall trial population, Stage IB through IIIA, a key secondary endpoint, demonstrated a reduction in the risk of disease recurrence or death of 79% (based on a HR of 0.21; 95% CI 0.16, 0.28; p<0.0001).
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ASCO, Author Interviews, Cancer Research / 12.06.2020

MedicalResearch.com Interview with: Alex Spira, MD, PhD, FACP Medical Oncologist Virginia Cancer Specialists and Chair of the US Oncology Research Executive Committee MedicalResearch.com: What is the background for this study? Would you explain what the conjugate consists of and what types of cancer it may target? What are the main findings? Response: The concept of the CX072 and CX2029 studies is that they use what’s called a probody molecule that gets broken down only at the tumor site. This is completely novel in that it helps diminish toxicity by not having less systemic absorption. In the case of CX2029, this target was previously undruggable, meaning the systemic toxicity was too high. By limiting it to activity at the tumor, that is significantly abated. (more…)
ASCO, Author Interviews, OBGYNE, Ovarian Cancer / 12.06.2020

MedicalResearch.com Interview with: Robert L. Coleman, MD, FACOG, FACS Chief Scientific Officer US Oncology Research MedicalResearch.com: What is the background for this study? Response: For years, there has been general support for surgery in patients with recurrent ovarian cancer supported by reams of retrospective studies that suggest patients live longer if they have surgery preceding chemotherapy. Suggested hypotheses from these trials were that patients most likely to benefit from the procedure were those with good performance status (could tolerate the procedure), had long platinum-free interval (surrogate for potential for chemotherapy response) and those in whom all disease could be resected. Each of these are also characteristics that would portend a good prognostic cohort in general and would likely do better than other patients without these characteristics. So there was a strong selection bias in these retrospective surveys. Thus, the call for randomized trials. GOG-213 was launched in 2007 with 2 primary endpoints: 1. Determine the impact of adding bevacizumab to paclitaxel/carboplatin in patients with platinum-sensitive recurrent ovarian cancer, and 2. Determine if surgery increases overall survival. (more…)
ASCO, Author Interviews, Cancer Research, Colon Cancer / 04.06.2020

MedicalResearch.com Interview with: Salvatore Siena, MD Director, Falck Division of Medical Oncology Department of Hematology and Oncology, and Niguarda Cancer Center Grande Ospedale Metropolitano Niguarda, Milano, I Full Professor of Medical Oncology, Department of Oncology and Hemato-Oncology Università degli Studi di Milano MedicalResearch.com: What is the background for this study? Response: There remains a significant unmet clinical need in treating patients with HER2 positive advanced colorectal cancer (CRC) who progressed on previous therapies. Exploratory clinical studies in CRC with HER2-amplification documented that patients with tumors with this molecular characteristic may benefit from HER2-targeted therapies (reviewed in Siena S et al Ann Oncol 2018). In particular, the phase 1 DS8201-A-J101 dose-expansion study of the cohort of patients with HER2 expressing non-breast/non-gastric or HER2 mutant solid tumors who received the 6.4 mg/kg dose of T-DXd, there were 20 patients with CRC. In this studythe experimental drug T-DXd (trastuzumab deruxtecan) showed clinical benefit and manageable safety profile.
  • Investigator-assessed ORR (Objective Response Rate) of 15.0% (95% CI, 3.2-37.9), DCR (Disease Control Rate) of 80.0% (95% CI, 56.3-94.3), and median PFS (Progression Free Survival) of 4.1 months (95% CI, 2.1-5.9) was reported
  • Common TEAEs (Treatment Emergent Adverse Events) include gastrointestinal (low grade) and hematological, which is consistent with overall T-DXd safety profile across various tumors
  • ILD (Interstitial Lung Disease) was reported in 2 patients (Tsurutani et al. 2020)
Given the unmet need in the treatment of patients with HER2 positive advanced CRC who progressed on previous therapies and the clinical observations from the phase 1 DS8201-A-J101 study (see previous paragraph) , the phase 2 DESTINY-CRC01 trial was conducted to evaluate the efficacy and safety of T-DXd in patients with HER2 expressing CRC who were previously treated with at least 2 lines of therapy. (more…)
ASCO, AstraZeneca, Author Interviews, Breast Cancer, Cancer Research / 02.06.2020

MedicalResearch.com Interview with: Josefa Briceno, MD Medical Head, DDR/ADC Franchise AstraZenca MedicalResearch.com: What is the background for this study? What are the main findings? Response: In January 2018, the US FDA expanded the approved use of LYNPARZA to treat patients with HER2- negative metastatic breast cancer with germline BRCA mutations based on positive results from the Phase III OlympiAD trial, which demonstrated the benefit of LYNPARZA over standard of care in physician’s choice chemotherapy in this patient population. LUCY is a Phase IIIb interim analysis aimed to evaluate the clinical effectiveness and safety of LYNPARZA in a real-world setting and has been expanded to include a group of patients with somatic BRCA mutations. A total of 252 patients with HER2-negative metastatic breast cancer with germline BRCA mutations were enrolled in the open-label, single-arm, Phase IIIb study. Patients received a taxane and/or anthracycline in the (neo)adjuvant/metastatic setting, and ≤2 lines of chemotherapy. The primary end point of the study was investigator-defined progression-free survival (PFS), and secondary end points included overall survival, time to first subsequent therapy or death, and investigator-assessed clinical response rate. The interim analysis was planned to take place after 160 progression-free survival events. Overall, treatment lasted for a median of 7.9 months, and the median progression-free survival was 8.1 months (95% confidence interval of 6.9-8.7; 166 progression-free survival events). In addition, the median time to first subsequent therapy or death was 9.7 months (95% confidence interval of 8.7-11.1) and the investigator-assessed clinical response rate was 48.6% (95% confidence interval of 42.2-55.0). Adverse events of all grades were reported in >20% of patients were nausea, anemia, asthenia, vomiting, and fatigue. Grade ≥3 adverse events were reported in 24.6% of patients, and 4.4% of patients had an adverse event that led to treatment discontinuation. (more…)
ASCO, AstraZeneca, Author Interviews, Cancer Research, Ovarian Cancer / 02.06.2020

MedicalResearch.com Interview with: Mark Sims US Franchise Head Women’s Cancer & DNA Damage Response AstraZeneca MedicalResearch.com: What is the background for this study? What are the main findings? Response: SOLO2 is a Phase III, randomized, double-blind, multicenter trial designed to determine the efficacy and safety of LYNPARZA tablets as a maintenance monotherapy compared with placebo, in patients with platinum-sensitive relapsed or recurrent gBRCA-mutated (BRCAm) ovarian cancer. The trial included 295 patients with germline BRCA1 or BRCA2 mutations who had received at least 2 prior lines of platinum-based chemotherapy and were in complete or partial response. The trial met its primary endpoint in October 2016, showing maintenance treatment with LYNPARZA significantly improved progression-free survival to a median of 19.1 months vs 5.5 months with placebo (a hazard ratio of 0.30; a 95% confidence interval of 0.22 to 0.41; a p value of <0.0001). (more…)
ASCO, Author Interviews, Cancer Research / 30.05.2020

MedicalResearch.com Interview with: Cardinale Smith, MD, PhD Associate Professor Medicine, Hematology and Medical Oncology and Geriatrics and Palliative Medicine Icahn School of Medicine at Mount Sinai New York MedicalResearch.com: What is the background for this study? Response: Cancer patients are often hospitalized with complications from cancer and cancer treatment. Physical decline is common among hospitalized cancer patients and contributes to poorer outcomes including increased length of stay, excess days, readmissions and patient experiences. Therefore, increased activity and mobilization during hospitalization are essential to prevent functional decline. Whereas previous research has focused on risk factors that limit mobility and interventions for enhancing mobility in well-functioning, community dwelling older adults, there have been limited interventions on the mobility of hospitalized cancer patients. (more…)
ASCO, Author Interviews, Biomarkers, Breast Cancer / 30.05.2020

MedicalResearch.com Interview with: Francois-Clement Bidard, MD PhD Head of Breast Cancer Group, Institut Curie Professor of Med. Oncology, UVSQ/Paris MedicalResearch.com: What is the background for this study? Response: A timely question is how to optimize the endocrine therapy of ER+ HER2- metastatic breast cancers? Aromatase inhibitors (AI) are currently the standard of care in first line, in combination with CDK4/6 inhibitors. Mutations in the estrogen receptor gene (ESR1) can be detected in up to 40% of AI-resistant metastatic breast cancers, but no data was available in the current first line setting (AI combined to CDK4/6 inhibitor). This exploratory study of the first line PADA-1 study reports on the detection rate of ESR1 mutations in cell-free DNA from an “AI-sensitive” population (with no metastatic relapse during adjuvant AI therapy), before the start of therapy (at inclusion). As expected, we found a low prevalence of 3.2% in the general population (N=1,017 patients included). The prevalence of ESR1 mutations among subgroups appeared primarily driven by the type of adjuvant endocrine therapy: patients with prior exposure to adjuvant therapy with AI displayed the highest prevalence of ESR1 mutations (7.1%), followed by patients with no prior adjuvant endocrine therapy (mostly de novo stage IV; ESR1 mutation prevalence: 2.4%). Patients who received adjuvant endocrine therapy with no AI (e.g. tamoxifen only) had the lowest ESR1 mutation prevalence (1.2%). (more…)
ASCO, Author Interviews, Cancer Research, Electronic Records / 30.05.2020

MedicalResearch.com Interview with: Debra A. Patt, MD, PhD, MBA, FASCO Editor-in-chief of the Journal of Clinical Oncology - Clinical Cancer Informatics Medical oncologist at Texas Oncology, and US Oncology Research Breast Cancer Committee member MedicalResearch.com: What is the background for this study? Response: Cancer care is increasing in complexity with differentiation of cancer subtypes, new treatments, and treatment sequences and combinations. Complying with evidence based therapy has become an increasing challenge. We see that compliance with guideline based care across the country is highly variable. Our study evaluated an electronic health record based Clinical Decision Support System to facilitate compliance with evidence based guidelines--or pathways--to deliver care to adult patients with cancer. (more…)
ASCO, Author Interviews, Cancer Research, Leukemia, UC Davis / 28.05.2020

MedicalResearch.com Interview with: Brian A. Jonas, M.D., Ph.D. UC Davis Health System MedicalResearch.com: What is the background for this study? At this year’s American Society of Clinical Oncology (ASCO) and European Hematology Association (EHA) virtual meetings, we presented data on the rapidity and likelihood of response to venetoclax treatments, and its associated characteristics, in older patients with newly diagnosed acute myeloid leukemia (AML). We evaluated data from two clinical trials of venetoclax in combination with azacitidine, or decitabine (M14-358), or low-dose cytarabine (LDAC) (M14-387) in this patient population. (more…)
ASCO, Author Interviews, Cancer Research / 19.05.2020

MedicalResearch.com Interview with: Dr. Jesus G. Berdeja, MD Director of Myeloma Research Sarah Cannon Nashville, TN MedicalResearch.com: What is the background for this study? Response: Despite many advances in the treatment of multiple myeloma in recent years, the majority of patients will progress through all available therapies and ultimately succumb to their disease. Thus there is still a high unmet medical need. The Phase 1b/2 CARTITUDE-1 study evaluates the safety and efficacy of JNJ-4528, an investigational BCMA-directed CAR-T therapy, in the treatment of patients with relapsed or refractory multiple myeloma. Participants in this study have already tried approved therapies, and had received a median of five prior treatment regimens and their median overall survival is less than 12 months. (more…)