HKT288 / Novartis - LARVOL DELTA

Impact of the time of initiation and line of biologic therapy on the retention rate of Secukinumab (SECU) in axial spondyloarthritis (axSpA). Data from the French multicenter retrospective FORSYA study (EULAR 2023) - "Study periods : Two cohorts were evaluated with regard to the time of initiation of SECU: Cohort (C1) : between August 11 th , 2016 (time of the launch of SECU in France) and Aug 3 st 2018; Cohort 2 (C2) : between sept 1 st 2018 and Nov 13, 2020 (remotely from the launch). † See Methods for explanation # without imputation for missing data $ Adjustment on: C1 (OSI, IBD, History of depression or anti-depressive concomitant treatment); C2 (OSI, History of depression or anti-depressive concomitant treatment, disease duration, corticosteroids) Interpretation HR > 1: the hazard of discontinuation at 1 year is X times higher vs reference L = Line of biologic therapy Conclusion These data showing a better retention rate at 1 year remotely from the launch of SECU, probably explained by its use at an earlier stage of the disease, suggest a change in the behavior of prescribing physicians probably reflecting a better confidence in this treatment. These data also underline the..."

Retrospective data • Ankylosing Spondylitis • CNS Disorders • Depression • Dermatology • Fibromyalgia • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Arthritis • Inflammatory Bowel Disease • Musculoskeletal Pain • Ocular Inflammation • Ophthalmology • Pain • Psoriasis • Psoriatic Arthritis • Psychiatry • Seronegative Spondyloarthropathies • Spondylarthritis • Uveitis

Phase I/II study of spartalizumab (PDR001), an anti-PD1 mAb, in patients with advanced melanoma or non-small cell lung cancer (ESMO 2018) - P1/2; " As of Nov 13, 2017, 61 pts with melanoma received 400 mg spartalizumab Q4W; 36% of pts were treatment-naïve, 20% had ≥2 prior therapies, and all were anti-PD(L)1-naïve. Spartalizumab was well tolerated with a manageable safety profile. Efficacy was observed in pts with NSCLC (Q3W and Q4W) and melanoma (Q4W), and was as expected given the high proportion of pts with PD-L1– disease. ORRs were higher in PD-L1+ pts, corroborating previous findings that PD-L1 expression enriches for response to anti-PD1 agents in certain tumor types."

Clinical • IO Biomarker • P1/2 data • PD(L)-1 Biomarker • Melanoma • Non Small Cell Lung Cancer

Subsequent anticancer medication following first-line lenvatinib: A posthoc responder analysis from the phase 3 REFLECT study in unresectable hepatocellular carcinoma. (ASCO-GI 2019) - P3; "NCT01761266; Background: Lenvatinib (LEN) was shown to be noninferior to sorafenib (SOR) for overall survival (OS) in REFLECT (median OS [mOS], 13.6 vs 12.3 months [mo]; HR 0.92; 95% CI 0.79–1.06)...Data cutoff: Nov 13, 2016... In REFLECT, one third of pts randomized to first-line LEN received subsequent anticancer medication, including SOR, with a mOS of 21 mo. In this exploratory, posthoc analysis of pts who responded to LEN and received any subsequent anticancer medication or SOR, mOS was 26 mo."

Clinical • P3 data • Retrospective data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Subsequent anticancer procedures following first-line lenvatinib (LEN): A post hoc analysis from the phase III REFLECT study in unresectable hepatocellular carcinoma (uHCC). (ASCO-GI 2020) - P3; "REFLECT was a phase 3 study comparing the efficacy and safety of LEN versus sorafenib (SOR) in first-line treatment of patients (pts) who have uHCC...Pts were followed-up every 12 weeks until data cutoff (Nov 13, 2016) or death... Pts randomized to first-line LEN who received subsequent anticancer procedures had longer OS compared with the similar sequence for pts taking first-line SOR. Clinical trial information: NCT01761266. Research Funding: This study was sponsored by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co."

Clinical • P3 data • Retrospective data

Subsequent anticancer medication following first-line lenvatinib: A posthoc responder analysis from the phase 3 REFLECT study in unresectable hepatocellular carcinoma. (ASCO-GI 2019) - P3; "NCT01761266; Background: Lenvatinib (LEN) was shown to be noninferior to sorafenib (SOR) for overall survival (OS) in REFLECT (median OS [mOS], 13.6 vs 12.3 months [mo]; HR 0.92; 95% CI 0.79–1.06)...Data cutoff: Nov 13, 2016... In REFLECT, one third of pts randomized to first-line LEN received subsequent anticancer medication, including SOR, with a mOS of 21 mo. In this exploratory, posthoc analysis of pts who responded to LEN and received any subsequent anticancer medication or SOR, mOS was 26 mo."

Clinical • P3 data • Retrospective data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

A Phase 1 Study of a CDH6-Targeting Antibody-Drug Conjugate in Patients with Advanced Solid Tumors with Evaluation of Inflammatory and Neurological Adverse Events. (PubMed, Oncol Res Treat) - P1 | "Preclinical toxicology did not predict the neurotoxicity observed with HKT288, and a comprehensive assessment performed post hoc did not identify the mechanism of toxicity. The development of further CDH6-targeting ADCs should be pursued with caution."

Adverse events • Clinical • Journal • P1 data • CNS Disorders • Constipation • Epilepsy • Fatigue • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor

Safety and immunogenicity of inactivated poliovirus vaccine schedules for the post-eradication era: a randomised open-label, multicentre, phase 3, non-inferiority trial. (PubMed, Lancet Infect Dis) - P3 | "Our observations suggest that adequate immunity against poliovirus type 1 and type 2 is provided by two doses of either IPV or f-IPV at 14 and 36 weeks of age, and broad immunity is provided with three doses of f-IPV, enabling substantial savings in cost and supply. These novel clinical data will inform global polio immunisation policy for the post-eradication era."

Clinical • Head-to-Head • Journal • P3 data • Allergy • Immunology

"G20 finance leaders to debate debt relief on Nov 13, says Japan's Aso https://t.co/Qg8ckRhihc" (@Reuters)

"#COVID19WI Nov 13, 2020" (@mtmdphd)

Infectious Disease • Novel Coronavirus Disease

"5-day virtual #AHA2020 Nov 13-17!! Registration link ⬇️" (@MonteHeart)

Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. (PubMed, Lancet HIV) - P3 | "These week 96 data support bictegravir, emtricitabine, and tenofovir alafenamide as a safe, well tolerated, and durable treatment for people living with HIV-1 with no emergent resistance."

Clinical • Head-to-Head • Journal • P3 data • Gene Therapies • Hepatitis B • Immunology • Infectious Disease • Renal Disease

Co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. (PubMed, Lancet HIV) - P3 | "These week 96 data support bictegravir, emtricitabine, and tenofovir alafenamide as a safe, well tolerated, and durable treatment for people living with chronic HIV."

Clinical • Head-to-Head • Journal • P3 data • Cardiovascular • Congestive Heart Failure • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Gene Therapies • Heart Failure • Hematological Disorders • Hematological Malignancies • Hepatitis B • Immunology • Infectious Disease • Oncology • Pulmonary Embolism • Renal Disease

Regulation of terpenoid biosynthesis by miRNA in Persicaria minor induced by Fusarium oxysporum. (PubMed, BMC Genomics) - "Our findings suggest that six studied miRNAs post-transcriptionally regulate terpenoid biosynthesis in P. minor. This regulatory behaviour of miRNAs has potential as a genetic tool to regulate terpenoid biosynthesis in P. minor."

Journal

"What would you do? Register for the SOSS if you want to join us live in Nashville to discuss! Nov 13 5pm" (@KimrynRathmell)

"MORE: William Taylor, George Kent and Marie Yovanovitch will appear Nov 13, 15" (@Reuters)

Post-progression therapy after lenvatinib first-line therapy: a post-hoc responder analysis of phase 3 REFLECT study in unresectable hepatocellular carcinoma (HCC) (DGHO 2019) - "Introduction: Lenvatinib (LEN) was shown to be noninferior to sorafenib (SOR) for overall survival (OS) in REFLECT (median OS [mOS], 13.6 vs 12.3 months [mo]; HR 0.92; 95% CI 0.79-1.06)...Data cutoff: Nov 13, 2016... In REFLECT, one-third of patients randomized to first-line LEN received subsequent anticancer medication, including SOR, with a mOS of 21 mo. In this exploratory post hoc analysis of patients who responded to LEN and received any subsequent anticancer medication or SOR, mOS was 26 mo."

Clinical • P3 data • Retrospective data

An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. (PubMed, Lancet Haematol) - P1/2; "Oral decitabine plus cedazuridine emulated the pharmacokinetics of intravenous decitabine, with a similar safety profile and dose-dependent demethylation. Clinical responses were similar to intravenous decitabine treatment for 5 days. Further study of decitabine plus cedazuridine as an alternative to parenteral therapy or in combination with other new oral agents for myeloid disorders is warranted."

Clinical • Journal • P1 data

Overlap of the Pitt–Hopkins and Lennox-Gastaut syndromes (CONy 2019) - "2018 Nov 13. doi: 10.1007/s13760-018-1045-2)."