Vynfinit (vintafolide) / Novartis - LARVOL DELTA

Folate Receptor Alpha-A Secret Weapon in Ovarian Cancer Treatment? (PubMed, Int J Mol Sci) - "We summarize the mechanisms of the action of various therapeutic strategies based on FRα, including MABs (monoclonal antibodies), ADCs (antibody-drug conjugates), FDCs (folate-drug conjugates), SMDCs (small molecule-drug conjugates), vaccines, and CAR-T (chimeric antigen receptor T) cells, and present the most significant clinical trials of some FRα-based drugs. Furthermore, we discuss the pros and cons of different FR-based therapies, highlighting mirvetuximab soravtansine (MIRV) as the currently most promising EOC-targeting drug."

Biomarker • IO biomarker • Journal • Review • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

The Royal Flying Doctor Service Initiation of Helicopter Video Simulation Orientation Training for Air Medical Crews in Western Australia: A Pilot Study. (PubMed, Air Med J) - "Implementing a comprehensive educational strategy including classroom and practical elements for clinical staff in their orientation to new aircraft improves their confidence in performing critical care procedures if required in flight. The addition of in-flight prerecorded videos demonstrating these critical care procedures is a useful adjunct to simulation training for flight crew in air medical retrieval, and further analytical studies may indeed show a statistically significant improvement in staff confidence."

Journal • Video • Critical care

Integrating antibody drug conjugates in the management of gynecologic cancers. (PubMed, Int J Gynecol Cancer) - "The clinical development of antibody drug conjugates (ADCs) in ovarian cancer began in 2008 with farletuzumab, a humanized monoclonal antibody, and vintafolide, an antigen drug conjugate, both targeting alpha folate receptor...In September 2021, the FDA approved tisotumab vedotin (TV) in recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. This was followed in November 2022, by the approval of mirvetuximab soravtansine (MIRV) for adult patients with folate receptor alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens...We also outline new concepts in the field of ADCs, including promising targets such as NaPi2 and novel drug delivery platforms such as dolaflexin with a scaffold-linker. Finally, we briefly present challenges in the clinical management of ADC toxicities and the emerging role of ADC combination..."

Journal • Review • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Uterine Cancer • FOLR1 • HER-2

Active Targeted Nanoformulations via Folate Receptors: State of the Art and Future Perspectives. (PubMed, Pharmaceutics) - "Two strategies have been used to achieve this folate receptor targeting: (i) the use of ligands with high affinity to FRs (e.g., folic acid or anti-FRs monoclonal antibodies) linked to the therapeutic agents or (ii) the use of nanocarriers whose surface is decorated with these ligands and in which the drug is encapsulated. This manuscript analyzes the use of FRs as a target to develop new therapeutic tools in the treatment of cancer and inflammatory diseases with an emphasis on the nanoformulations that have been developed for both therapeutic and imaging purposes."

Journal • Review • Immunology • Inflammation • Inflammatory Arthritis • Oncology • Ovarian Cancer • Rheumatoid Arthritis • Rheumatology • Solid Tumor

Study for Women With Platinum Resistant Ovarian Cancer Evaluating EC145 in Combination With Doxil® (PROCEED) (clinicaltrials.gov) - P3; N=441; Terminated; Sponsor: Endocyte; N=640 ➔ 441; Suspended ➔ Terminated; DSMB decision

Clinical • Combination therapy • Enrollment change • Trial termination • Oncology • Ovarian Cancer • Solid Tumor

TARGET: Phase 2 Study of EC145 Alone Versus EC145+Docetaxel Versus Docetaxel Alone in Participants With FR(++) 2nd Line Non Small Cell Lung Cancer (clinicaltrials.gov) - P2; N=203; Active, not recruiting; Sponsor: Merck Sharp & Dohme Corp.; Completed ➔ Active, not recruiting

Clinical • Enrollment closed • P2 data • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MRI

TARGET: Phase 2 Study of EC145 Alone Versus EC145+Docetaxel Versus Docetaxel Alone in Participants With FR(++) 2nd Line Non Small Cell Lung Cancer (clinicaltrials.gov) - P2; N=203; Active, not recruiting; Sponsor: Merck Sharp & Dohme Corp.

Clinical • New P2 trial • P2 data • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MRI

TARGET: Phase 2 Study of EC145 Alone Versus EC145+Docetaxel Versus Docetaxel Alone in Participants With FR(++) 2nd Line Non Small Cell Lung Cancer (clinicaltrials.gov) - P2; N=203; Completed; Sponsor: Endocyte; Active, not recruiting ➔ Completed

Clinical • P2 data • Trial completion • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MRI

First Report of Atypical Scab Caused by Venturia asperata on Apple in China. (PubMed, Plant Dis) - "BLAST analysis showed that the amplified sequences were identical and had 99.3% sequence identity with V. asperata (AF333447, MT459450 and MT459451), 95.4% sequence identity with V. cerasi (MK810963 and MK810964) and 94.3% sequence identity with V. carpophila (MN958609, MN958610 and MN958611)...To the best of our knowledge, this is the first report of V. asperata associated with apple scab-like lesions in China. This information augments our knowledge of the spectrum of Venturia species associated with disease on apple fruit and will be a valuable foundation underpinning management strategies for this cultivar."

Journal

Pre-clinical studies of EC2629, a highly potent folate- receptor-targeted DNA crosslinking agent. (PubMed, Sci Rep) - "Folate receptor (FR)-targeted small molecule drug conjugates (SMDCs) have shown promising results in early stage clinical trials with microtubule destabilizing agents, such as vintafolide and EC1456...Complete responses were also observed against FR-positive paclitaxel (KB-PR) and cisplatin (KB-CR) resistant models. When evaluated against FR-positive patient derived xenograft (PDX) models of ovarian (ST070), endometrial (ST040) and triple negative breast cancers (ST502, ST738), EC2629 showed significantly greater anti-tumor activity compared to their corresponding standard of care treatments. Taken together, these studies thus demonstrated that EC2629, with its distinct DNA reacting mechanism, may be useful in treating FR-positive tumors, including those that are classified as drug resistant."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

J&J’s Doxil/Caelyx shortages affect ovarian cancer trials (Financial Times) - J&J limited supply of Doxil/Caelyx is impacting Amgen’s TRINOVA-2 & Endocyte’s PROCEED in ovarian cancer; The supply of doxorubicin for independent pharmaceutical companies is currently on hold due to unplanned down time because of production equipment failures at the contract manufacturing firm Ben Venue Laboratories

Product shortage • Oncology • Ovarian Cancer

[Late breaking abstract] TARGET: A randomized, phase II trial comparing vintafolide versus vintafolide plus docetaxel, versus docetaxel alone in second-line treatment of folate-receptor-positive non-small cell lung cancer (NSCLC) patients (ESMO 2014) - Presentation time: 27.09.2014, 16:00 - 17:45; Abstract #LBA40_PR; P2, N=199; NCT01577654; Sponsor: Merck; "With the pre-specified stratified analysis adjusting for baseline factors (time since last chemotherapy, best response and stage), the OS HR for vintafolide+DTX vs. DTX were 0.75 (1-sided p=0.1066) for all patients, and 0.51 (1-sided p=0.0147) for the predefined adenocarcinoma patient subgroup....Vintafolide+DTX showed clinically meaningful improvement across all efficacy endpoints (ORR, PFS and OS) over single-agent DTX,...."

P2 data • Non Small Cell Lung Cancer • Oncology

Merck: Annual Report 2013 (Merck (MSD)) - Anticipated patent expiry in US in 2024

Anticipated patent expiry • Ovarian Cancer

Merck and Endocyte enter exclusive worldwide agreement to develop and commercialize phase III cancer candidate Vintafolide (EC145) (Endocyte) - Merck & Endocyte announce they have entered into an agreement to develop & commercialize Endocyte's novel investigational therapeutic candidate vintafolide (EC145); Vintafolide is currently being evaluated in a P3 clinical trial for platinum-resistant ovarian cancer, (PROCEED trial) & a P2 trial for cancer NSCLC

Commercial agreement • Non Small Cell Lung Cancer • Ovarian Cancer

Q2 ’11 Results (Endocyte) - EC145 / Endocyte; Anticipated P2 trial initiation; Anticipated EU MAA in Q1 ’12

Anticipated P2 trial initiation • MAA filing • Oncology

PRECEDENT subset analysis: safety and disease control with vintafolide monotherapy following discontinuation of pegylated liposomal doxorubicin (PLD) (ESMO 2014) - Presentation time: 27.09.2014, 12:45 - 13:45; Abstract #894P; P2, N=149; PRECEDENT (NCT00722592); "Twenty-two pts from the combination arm discontinued PLD and continued on Vinta alone. The most common reasons for PLD discontinuation were maximum permitted dose (n=6) and hand-foot syndrome (n=9). Median number of cycles of Vinta alone was 4 (range: 1-16). In pts receiving only Vinta, median time from monotherapy to progression, death, or treatment discontinuation was 4.3 months, and median survival time was 18 months."

P2 data • Ovarian Cancer

Endocyte reports fourth quarter and year end 2011 financial results and operations update (Endocyte) - First pt enrollment in P2b/3 NSCLC trial in early Q2 2012

Anticipated patient enrollment • Non Small Cell Lung Cancer

Endocyte: Q3 2014 Results (Endocyte) - Anticipated final OS data from P2b TARGET trial for NSCLC by early 2015; Anticipated initiation of P3 trial for NSCLC in H1 2015

Anticipated new P3 trial • Anticipated P2b data • Non Small Cell Lung Cancer • Oncology

A Study of MK-8109 (Vintafolide) Given Alone or With Chemotherapy in Participants With Advanced Cancers (MK-8109-001) (clinicaltrials.gov) - P1; N=37; Terminated; Sponsor: Merck Sharp & Dohme Corp.; N=94 -> 37 ; Active, not recruiting -> Terminated

Enrollment change • Trial termination • Biosimilar • Oncology • Prostate Cancer

Merck: ASCO 2013 (Merck (MSD) Press Release) - Anticipated regulatory submission in US based on P3 PROCEED trial for platinum-resistant ovarian cancer in 2015

Anticipated FDA event • Ovarian Cancer

Endocyte reports first quarter financial results and provides clinical update (Endocyte Press Release) - P2, N=203; Sponsor: Merck Sharp & Dohme Corp; NCT01577654; “Full results of Phase 2b TARGET trial, including latest overall survival data, to be presented at an upcoming medical conference in 2014.”

Anticipated P2 data • Non Small Cell Lung Cancer

A dose finding study with oral LDK378 in patients with tumors characterized by genetic abnormalities in anaplastic lymphoma kinase (ALK) (clinicaltrials.gov) - P1, N=70

Not yet recruiting → Recruiting

Company Presentation (Endocyte) - "Met primary endpoint of clinical benefit & significant improvements in OS in FR (++) patients"

P2 data • Non Small Cell Lung Cancer

In vivo Pharmacokinetics and Pharmacodynamics of ZTI-01 (Fosfomycin for Injection) in the Neutropenic Murine Thigh Infection Model against E. coli, K. pneumoniae, and P. aeruginosa. (PubMed) - Antimicrob Agents Chemother - "Survival in mice infected with EC 145 was maximal at 24 h AUC/MIC exposures of 9-43, which is comparable to the stasis exposures identified in the PK/PD studies. These results should prove useful for the design of clinical dosing regimens for ZTI-01 in the treatment of serious infections due to Enterobacteriaceae and Pseudomonas."

Journal • Biosimilar • Immunology

Results of phase II PRECEDENT trial for investigational folate receptor therapy vintafolide in patients with platinum-resistant ovarian cancer published in Journal of Clinical Oncology (Merck (MSD) Press Release) - P2, N=162; PRECEDENT (NCT00722592); Sponsor: Merck; "...administration of vintafolide plus pegylated liposomal doxorubicin (PLD) versus PLD alone...resulted in a median progression-free survival (PFS) of 5.0 months compared to 2.7 months for those treated with PLD alone (HR=0.63; 95% CI 0.41–0.96; p=0.031) in the intent-to-treat (ITT) population....Median PFS benefit in...[patients shown to have folate receptor-positive tumors] was 5.5 months compared to 1.5 months for PLD alone (HR=0.38; 95% CI 0.17–0.85; p=0.013)."

P2 data • Ovarian Cancer