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Philippe Moreau, MD Of Nantes Faculty of Medicine Discusses Daratumumab Phase 3 Study: Could Be A Pivotal Study In The Approval Of Daratumumab In The United States, Europe, & Other Countries. BACKROUND: VTd is a standard of care (SoC) for TE NDMM. CD38 mAb DARA significantly reduced the risk of progression/death and improved CR and MRD-negative rates in relapsed refractory MM or transplant-ineligible NDMM in phase 3 studies. We report the primary and final analysis of Part 1 of CASSIOPEIA. METHODS: In Part 1, TE NDMM pts 18-65 y were randomized 1:1 to VTd (6 28-day cycles [C; 4 pre-ASCT…

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Philippe Moreau, MD Of Nantes Faculty of Medicine Discusses Daratumumab Phase 3 Study: Phase 3 Randomized Study Of Daratumumab + Bortezomib:Thalidomide:Dexamethasone (D-VTd) VS VTd In Transplant-Eligible NDMM. BACKROUND: VTd is a standard of care (SoC) for TE NDMM. CD38 mAb DARA significantly reduced the risk of progression/death and improved CR and MRD-negative rates in relapsed refractory MM or transplant-ineligible NDMM in phase 3 studies. We report the primary and final analysis of Part 1 of CASSIOPEIA. METHODS: In Part 1, TE NDMM pts 18-65 y were randomized 1:1 to VTd (6 28-day cycles [C; 4 pre-ASCT induction, 2 post-ASCT consolidation]…

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Kim Nguyen Chi MD Of The University Of British Colombia Discusses TITAN Study & Docetaxel: There Is Some Support To Using Apalutamide After Patients Received Docetaxel. BACKROUND: TITAN was designed to determine whether APA, a selective next-generation androgen receptor inhibitor, plus ADT improves radiographic progression-free survival (rPFS) and overall survival (OS) compared with PBO plus ADT in pts with mCSPC. METHODS: In this randomized, double-blind phase 3 study, pts with mCSPC regardless of extent of disease were randomized (1:1) to APA (240 mg/d) or PBO, added to ADT, in 28-day cycles. Pts with prior treatment (tx) for localized disease or…

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Kim Nguyen Chi MD Of The University Of British Colombia Discusses TITAN Study: Phase III Double-Blind, Randomized Study Of Apalutamide Versus Placebo In Patients With (mCSPC). BACKROUND: TITAN was designed to determine whether APA, a selective next-generation androgen receptor inhibitor, plus ADT improves radiographic progression-free survival (rPFS) and overall survival (OS) compared with PBO plus ADT in pts with mCSPC. METHODS: In this randomized, double-blind phase 3 study, pts with mCSPC regardless of extent of disease were randomized (1:1) to APA (240 mg/d) or PBO, added to ADT, in 28-day cycles. Pts with prior treatment (tx) for localized disease or…

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Dr. Luis Paz-Ares, MD, Phd of the Hospital Universitario 12 De Octubre gives a brief overview of his ASCO 2019 presentation in Spanish entitled Efficacy and safety profile of lurbinectedin in second-line SCLC patients: Results from a phase II single-agent trial. Abstract: Background: Lurbinectedin (L) is a novel anticancer drug that inhibits activated transcription and induces DNA double-strand breaks, leading to apoptosis. Methods: A multicenter phase 2 basket trial assessed the efficacy and safety of L in several cancer types, including small cell lung cancer (SCLC). Primary endpoint was confirmed overall response rate (ORR) by RECIST v.1.1. In the SCLC…

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Dr. Luiz Paz-Ares, MD, Phd of th Hospital Universitario 12 De Octubre gives a brief overview of his presentation from ASCO 2019 entitiled Efficacy and safety profile of lurbinectedin in second-line SCLC patients: Results from a phase II single-agent trial. Abstract: Background: Lurbinectedin (L) is a novel anticancer drug that inhibits activated transcription and induces DNA double-strand breaks, leading to apoptosis. Methods: A multicenter phase 2 basket trial assessed the efficacy and safety of L in several cancer types, including small cell lung cancer (SCLC). Primary endpoint was confirmed overall response rate (ORR) by RECIST v.1.1. In the SCLC cohort,…

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Josep Llovet, MD Of Mount Sinai School of Medicine Discusses Ramucirumab For Sorafenib Intolerant Patients With HCC: 8 Month Median Survival For Ramucirumab & Improved Quality Of Life, Now Approved By FDA. BACKROUND: Len, an inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor ?, RET, and KIT, is approved for first-line treatment of unresectable HCC (uHCC) based on the open-label phase 3 REFLECT study in which len showed noninferior overall survival (OS) and significantly improved objective response rate (ORR), progression-free survival (PFS), and time-to-progression (TTP) vs sorafenib. In the phase 2 KEYNOTE-224 study of pembro (a PD-1 inhibitor)…

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Josep Llovet, MD Of Mount Sinai School of Medicine Discusses Ramucirumab Study: Good Safety Profile & Patients With Aggressive Tumors Respond Certainly To RAM. BACKROUND: Len, an inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor ?, RET, and KIT, is approved for first-line treatment of unresectable HCC (uHCC) based on the open-label phase 3 REFLECT study in which len showed noninferior overall survival (OS) and significantly improved objective response rate (ORR), progression-free survival (PFS), and time-to-progression (TTP) vs sorafenib. In the phase 2 KEYNOTE-224 study of pembro (a PD-1 inhibitor) as second-line treatment of advanced HCC, pembro showed…

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Josep Llovet, MD Of Mount Sinai School of Medicine Discusses When To Use Ramucirumab: Second Line & Aggressive Tumors, Moving To Frontline In Combination With TKIs Next. BACKROUND: Len, an inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor ?, RET, and KIT, is approved for first-line treatment of unresectable HCC (uHCC) based on the open-label phase 3 REFLECT study in which len showed noninferior overall survival (OS) and significantly improved objective response rate (ORR), progression-free survival (PFS), and time-to-progression (TTP) vs sorafenib. In the phase 2 KEYNOTE-224 study of pembro (a PD-1 inhibitor) as second-line treatment of advanced…

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Alexa Schrock, PhD, of Foundation Medicine Discusses High Microsatellite Instability (MSI-H) in Colorectal Carcinoma Study: Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer. This study, published in Annals of Oncology, shows that tumor mutational burden (TMB) may help inform treatment decisions for MSI-H metastatic colorectal cancer patients. In the study, researchers found that TMB appears to be an important biomarker within this subset of patients and may be a predictor for whether these patients will respond to immunotherapy. The study supports the idea that further stratifying MSI-H metastatic colorectal cancer patients based…

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Alexa Schrock PhD Of Foundation Medicine Discusses How To Act On TMB Score: Patients Might Need A Higher TMB To Have a Great Response. BACKROUND: Microsatellite instability (MSI) is a biomarker for response to immune checkpoint inhibitors (ICPIs). PD-1 inhibitors in metastatic colorectal carcinoma (mCRC) with MSI-high (MSI-H) have demonstrated a high disease control rate and favorable progression-free survival (PFS); however, reported response rates to pembrolizumab and nivolumab are variable and often <50%, suggesting that additional predictive biomarkers are needed. METHODS: Clinicopathologic data were collected from patients with MSI-H mCRC confirmed by hybrid capture-based next-generation sequencing (NGS) treated with PD-1/L1…

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Dr. Celestia Higano, MD from the University of Washington discusses the PEACE III Trial Decreased Fracture Rate by Mandating Bone-protecting Agents in the EORTC 1333 Background: Skeletal fractures, pathological or not, are a frequent and underestimated side-effect of systemic treatment of metastatic castration resistant prostate cancer (mCRPC). The ERA223 trial (NCT02043678) was recently unblinded following the report of a significant increase in the fracture rates when abiraterone is combined with Ra223. Hence, FDA and EMA advised against this combination. The question whether mandated use of bone protecting agents (BPA), zoledronic acid or denosumab, would have mitigated the fracture risk and…

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Dr. Celestia Higano, MD of the University of Washington discusses the Alliance A031201 a phase III trial of enzalutamide (ENZ) versus enzalutamide, abiraterone, and prednisone (ENZ/AAP) for metastatic castration resistant prostate cancer (mCRPC) Background: Androgen receptor (AR) signaling is an important growth mechanism in mCRPC, providing the rationale for treatment with AR axis inhibitors such as ENZ and AAP. Targeting AR with anti-androgens such as ENZ can result in compensatory autocrine and paracrine androgenic stimulation. Therefore, using ENZ with the androgen biosynthesis inhibitor AAP to dampen these resistance mechanisms could improve clinical outcomes relative to ENZ alone. Methods: Men with…

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Dr. Celestia Higano, MD of the University of Washington discusses the Titan Trial Apalutamide vs Placebo During Androgen-Deprivation Therapy for Metastatic Castration-Sensitive Prostate Cancer. At 22.6-month follow-up, 66% of patients in the apalutamide group and 46% of patients in the placebo group remained on treatment. Apalutamide improved radiographic progression-free survival (hazard ratio [HR] = 0.48, 95% confidence interval [CI] = 0.390.60; P < .0001), with a 52% reduction in risk of death or radiographic progression; that benefit was observed across all subgroups analyzed. The median radiographic progression-free survival was not reached in the apalutamide group and was 22.1 months in…

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David M. Cognetti MD @KimmelCancerCtr Of Sidney Kimmel Cancer Center Discusses Photoimmunotherapy (PIT) Phase 2 Study Results: 30 Patients With A 43 ORR & OS Of 9.2 Months, Phase 3 Study Is Being Fast-Tracked. BACKGROUND: Patients with rHNSCC who have failed standard of care have poor prognoses and limited therapeutic options. In this study, final results are reported of a phase 2a trial of photoimmunotherapy (PIT) with a targeted drug RM-1929, consisting of the EGFR-directed antibody cetuximab conjugated to a photoactivatable dye (IRDye 700DX). Binding of the antibody-dye conjugate to cancer cells followed by photoactivation with nonthermal red light induces…

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David M. Cognetti MD @KimmelCancerCtr Of Sidney Kimmel Cancer Center Discusses Photoimmunotherapy (PIT) Phase 2 Study: Multicenter, Open-Label, Study Of RM-1929 Photoimmunotherapy (PIT) In Patients With Locoregional, Recurrent Head & Neck Squamous Cell Carcinoma (rHNSCC). BACKGROUND: Patients with rHNSCC who have failed standard of care have poor prognoses and limited therapeutic options. In this study, final results are reported of a phase 2a trial of photoimmunotherapy (PIT) with a targeted drug RM-1929, consisting of the EGFR-directed antibody cetuximab conjugated to a photoactivatable dye (IRDye 700DX). Binding of the antibody-dye conjugate to cancer cells followed by photoactivation with nonthermal red light…

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David M. Cognetti MD @KimmelCancerCtr Of Sidney Kimmel Cancer Center Discusses Photoimmunotherapy (PIT) Phase 3 Study: Opening Now To Compare Directly To Standard Of Care Chemotherapy. BACKGROUND: Patients with rHNSCC who have failed standard of care have poor prognoses and limited therapeutic options. In this study, final results are reported of a phase 2a trial of photoimmunotherapy (PIT) with a targeted drug RM-1929, consisting of the EGFR-directed antibody cetuximab conjugated to a photoactivatable dye (IRDye 700DX). Binding of the antibody-dye conjugate to cancer cells followed by photoactivation with nonthermal red light induces selective and rapid necrosis of the cancer cells,…

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David M. Cognetti MD @KimmelCancerCtr Of Sidney Kimmel Cancer Center Discusses Photoimmunotherapy (PIT): Superior To Photodynamic Therapy Due To The Light Sensitizer Being Conjugated To Erbitux. BACKGROUND: Patients with rHNSCC who have failed standard of care have poor prognoses and limited therapeutic options. In this study, final results are reported of a phase 2a trial of photoimmunotherapy (PIT) with a targeted drug RM-1929, consisting of the EGFR-directed antibody cetuximab conjugated to a photoactivatable dye (IRDye 700DX). Binding of the antibody-dye conjugate to cancer cells followed by photoactivation with nonthermal red light induces selective and rapid necrosis of the cancer cells,…

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David M. Cognetti MD @KimmelCancerCtr Of Sidney Kimmel Cancer Center Discusses Photoimmunotherapy Technology: Very Straight forward From A Technical Standpoint, 5 Minutes Per Light Application, Tumor Necrosis Seen Within Hours. BACKGROUND: Patients with rHNSCC who have failed standard of care have poor prognoses and limited therapeutic options. In this study, final results are reported of a phase 2a trial of photoimmunotherapy (PIT) with a targeted drug RM-1929, consisting of the EGFR-directed antibody cetuximab conjugated to a photoactivatable dye (IRDye 700DX). Binding of the antibody-dye conjugate to cancer cells followed by photoactivation with nonthermal red light induces selective and rapid necrosis…

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Luis G. Paz-Ares, MD, Phd provides an overview of his presentation at ASCO 2019 entitled Efficacy and safety profile of lurbinectedin in second-line SCLC patients: Results from a phase II single-agent trial. In addition, two experts (Rafael Santana-Davila MD of Seattle Cancer Care Alliance and Taofeek Owonikoko MD, PhD, MSCR of the Emory Winship Cancer Institute) give their opinions and a roundtable discussion of the data. Author(s): Luis G. Paz-Ares, Jose Manuel Trigo Perez, Benjamin Besse, Victor Moreno, Rafael Lopez, Maria Angeles Sala, Santiago Ponce Aix, Cristian Marcelo Fernandez, Mariano Siguero, Carmen Maria Kahatt, Ali Hassan Zeaiter, Khalil Zaman, Valentina…

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Luis G. Paz-Ares, MD, Phd provides an overview of his presentation at ASCO 2019 entitled Efficacy and safety profile of lurbinectedin in second-line SCLC patients: Results from a phase II single-agent trial. In addition, two experts (Rafael Santana-Davila MD of Seattle Cancer Care Alliance and Taofeek Owonikoko MD, PhD, MSCR of the Emory Winship Cancer Institute) give their opinions and a roundtable discussion of the data. Author(s): Luis G. Paz-Ares, Jose Manuel Trigo Perez, Benjamin Besse, Victor Moreno, Rafael Lopez, Maria Angeles Sala, Santiago Ponce Aix, Cristian Marcelo Fernandez, Mariano Siguero, Carmen Maria Kahatt, Ali Hassan Zeaiter, Khalil Zaman, Valentina…

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Ahmad Tarhini Md, PhD of the Winship Cancer Center discusses the United States Intergroup E1609 A phase III randomized study of adjuvant ipilimumab 3 or 10 mg kg versus high-dose interferon-?2b for resected high-risk melanoma. Background: Phase III adjuvant trials reported significant benefits in relapse-free survival (RFS) for 6 FDA-approved regimens and overall survival (OS) for HDI and ipi10 versus observation or placebo. E1609 evaluated the relative safety and efficacy of ipi at 3 and 10 mg/kg compared to HDI, which was the adjuvant standard until recently. Methods: E1609 had 2 co-primary endpoints: OS and RFS; considered positive if either…

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Charles Craddock MD PhD @charliecraddock of Queen Elizabeth Hospital discusses the Combination Lenalidomide and Azacitidine: A Novel Salvage Therapy in Patients Who Relapse After Allogeneic Stem-Cell Transplantation for Acute Myeloid Leukemia ABSTRACT PURPOSE Salvage options for patients who relapse after allogeneic stem-cell transplantation (allo-SCT) for acute myeloid leukemia (AML) and myelodysplasia (MDS) remain limited, and novel treatment strategies are required. Both lenalidomide (LEN) and azacitidine (AZA) possess significant antitumor activity effect in AML. Administration of LEN post-transplantation is associated with excessive rates of graft-versus-host disease (GVHD), but AZA has been shown to ameliorate GVHD in murine transplantation models. We therefore…

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Marcus Butler, MD discusses TBI-1301-Effect of minimal lymphodepletion prior to ACT with TBI-1301, NY-ESO-1 specific gene-engineered TCR-T cells, on clinical responses and CRS Background: Adoptive transfer of T cell receptor (TCR) gene-engineered T cells can induce durable anti-cancer responses. Post-infusion cytokine release syndrome (CRS) has been associated with clinical utility. Pre-infusion lymphodepletion (LD) may influence CRS, graft persistence, and clinical responses. While the optimal LD regimen is not yet defined, most include both cyclophosphamide (CY) and fludarabine (FLU). TBI-1301 is a novel gene therapy produced by engineering autologous lymphocytes to express an NY-ESO-1-specific TCR using a retrovirus vector that encodes…

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Marcus Butler, MD of Princess Margaret Cancer Centre discusses the ILLUMINATE 301 A randomized phase 3 study of tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced melanoma following progression on or after anti-PD-1 therapy Background: Tilsotolimod (IMO-2125) is a Toll-like receptor (TLR) 9 agonist with potent immunostimulating activity. In an ongoing Phase 1/2 clinical study in patients with advanced melanoma who progressed on or after anti-PD-1 therapy (NCT02644967), intratumoral (IT) tilsotolimod with ipilimumab was well-tolerated, demonstrating durable responses (including complete response > 21 months), dendritic cell activation, type I interferon response, CD8+ T-cell proliferation in…

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Philadelphia, PA (May 7, 2019) – Oncoceutics announced that the US Food and Drug Administration invited the company to present information regarding its lead compound ONC201 at the public advisory committee meeting of the Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee on June 20, 2019.   The meeting will provide Oncoceutics with the opportunity to present its clinical data for patients treated with ONC201, including studies for both adult and pediatric patients with gliomas containing the H3 K27M mutation, a disease that has been recognized to be an area of high unmet medical need. Additionally, the meeting will enable Oncoceutics…

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