Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Mitogens

Clinical utility of ctDNA analysis for treatment decision

Use of ctDNA for KRAS, NRAS and BRAF testing prior to potential anti-EGFR monoclonal antibody treatment for metastatic colorectal cancer

Clinical utility of ctDNA analysis for treatment decision

Plasma circulating DNA analysis

Karen-Lise G Spindler

The present study will investigate the feasibility and clinical value of using circulating tumor DNA as selection for anti-epidermal growth factor receptor treatment for metastatic colorectal cancer.

The primary aim of this prospective study is to investigate if cfDNA in plasma is feasible and reliable for selection of mCRC patients who will benefit of anti-EGFR monoclonal antibody therapy

Secondary, to analyze developments in mutational status as reflected by cfDNA in plasma during therapy and at time of progression

Plasma samles for circulating DNA analysis

OPTImal PALliative Anti-epidermal Growth Factor Receptor Treatment in Metastatic Colorectal Cancer -

OPTImal PALliative Anti-epidermal Growth Factor Receptor Treatment in Metastatic Colorectal Cancer - Feasibility Study Investigating Circulating Tumor DNA for Treatment Decisions

Feasibility measures

Identification of wildtype or mutated status and results delivered to clinicians

* Initial clinical test results i.e. ctDNA mutations or wildtype status within 7 days
* Detailed mutation type characterization is provided retrospectively.

Failure parameters

* Quality of samples; PB \> 5%, CPP1 major loss \< 10%
* Transportation \> 3 week days
* Analysis \> 3 working days
* Total results delivered \> 7 days.

Retrospective comparison of tumor mutation and plasma mutation analysis at baseline

Rate of Ectoderm mutations at time of progression

Calcualted lead time between radiologically detected progression and molecular biologically detected ( by Ectoderm and other resistance mutations) in the ctDNA.

Karen-Lise Garm Spindler

Professor

Skin and Connective Tissue Diseases

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Phase 1b: With a 3+3 dose escalation design, enrollment in Phase 1b will proceed until the MTD has been defined or the highest dose level has been reached. OKI-179 will be administered on a 4-days-on/3-days-off schedule, while binimetinib will be administered BID continuously.

Phase 2: Patients will be treated with the RP2D.

OKI-179 + binimetinib

Ryan Sullivan, MD

The NAUTILUS study is a Phase 1b/2, multi-center, open-label study in which patients with activating mutations in the RAS pathway (Phase 1b) and patients with NRAS-mutated Melanoma (Phase 2) will be treated with a combination of oral OKI-179 combined with the MEK inhibitor binimetinib.

NAUTILUS: OKI-179 Plus Binimetinib in Patients With Advanced Solid Tumors in the RAS Pathway (Phase 1b) and NRAS-mutated Melanoma (Phase 2)

NAUTILUS: A Phase 1b/2 Study of OKI-179 Plus Binimetinib in Patients With Advanced Solid Tumors and Activating Mutations in the RAS Pathway (Phase 1b) and in Patients With Advanced NRAS-Mutated Melanoma (Phase 2)

Incidence and severity of DLTs will be measured in the DLT-evaluable population during Cycle 1.

AEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Changes from baseline through study treatment will be analyzed using NCI CTCAE version 5.0 grade criteria

Objective responses will be determined per RECIST version 1.1 criteria, and the ORR will be defined as the proportion of patients with the best overall confirmed response of complete response (CR) or partial response (PR) in the Efficacy-Evaluable Population

PK parameters will be measured based on plasma concentration-time data of OKI-179 and OKI-006

Objective responses will be determined per RECIST version 1.1 criteria, and the ORR will be defined as the proportion of patients with the best overall confirmed response of complete response (CR) or partial response (PR) in the Efficacy-Evaluable Population.

Clinical benefit will be defined as the best overall confirmed response of CR, PR or stable disease for at least 3 months. The CBR will be defined as the proportion of patients with clinical benefit in the Efficacy-Evaluable Population.

The DOR will be calculated for all patients achieving a confirmed CR or PR and will be defined as the time from first disease assessment of PR or CR (whichever is first recorded) to the end of response, defined as occurrence of PD, death due to any cause, or relapse from CR.

Progression-free survival will be defined as the time from the first administration of OKI-179 to the date of progression or death due to any cause.

AEs will be graded according to the NCI CTCAE version 5.0

OnKure, Inc.

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Esophageal Neoplasms

Carcinoma

Cholangiocarcinoma

Pancreatic Neoplasms

Carcinoma, Non-Small-Cell Lung

Thyroid Neoplasms

Thyroid Diseases

Stomach Neoplasms

Glioblastoma

Head and Neck Neoplasms

Lung Neoplasms

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Urinary Bladder Neoplasms

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Esophageal Cancer

Pancreatic Cancer

Ovarian Cancer

Bile Duct Cancer

Stomach Cancer

Ovarian Epithelial Cancer

Small Intestine Cancer

Ulixertinib (BVD-523) is an oral, first-in-class ERK1/2 inhibitor

Ulixertinib (BVD-523)

xCures Clinical Operations

Louis B Nabors, MD

Marshall Schreeder, MD

Jose Galeas, MD

David Palchak, MD

Richard M Green, MD

Michael Demeure, MD

Naveed Wagle, MD

Benjamin A Weinberg, MD

Jennifer E. Tseng, MD

Joshua Lukenbill, DO

Jon Olson, MD

Philip L. Brooks, MD

Mohammad Mobayed, MD

Nathan B. Green, DO

Seth Cohen, MD

Carl J. Minniti Jr., MD

Bonni Guerin, MD

MInsig Choi, MD

Manish Bhandari, MD

Rex Mowat, MD

Suresh Nair, MD

Elena G Chiorean, MD

The objective of this expanded access program is to provide ulixertinib (BVD-523) for compassionate use in advanced cancer patients with MAPK pathway-altered solid tumor(s), including but not limited to KRAS, NRAS, HRAS, BRAF, MEK, and ERK mutations who have incomplete response to or have exhausted available therapies.

Ulixertinib is available for treatment as monotherapy or in combination with other clinically tolerable agent(s), conditionally approved by the drug manufacturer.

Expanded Access to Ulixertinib (BVD-523) in Patients With Advanced MAPK Pathway-Altered Malignancies

Cancer Commons

xCures

Anti-Infective Agents

Formaldehyde

KRAS, NRAS and BRAF mutations will be analyzed in circulating plasma DNA using ONCOBEAM technique.

KRAS, NRAS et BRAF mutation analysis from circulating plasma DNA

MERLIN JEAN LOUIS

HARLE ALEXANDRE

GAVOILLE CELINE, oncologist

RAS genotyping is mandatory for the prescription of anti-EGFR (epidermal growth factor receptor) therapies in patients with metastatic colorectal cancer. The standard genotyping is assessed on formalin-fixed paraffin embedded tumour tissue. This study compares RAS and BRAF genotyping results achieved in analyzing circulating plasma DNA using OncoBEAM™ technique with those achieved using the standard genotyping techniques and formalin-fixed paraffin embedded samples.

The study will be proposed to all patients with a metastatic colorectal cancer.

Study information will be given to the patient during a routine medical examination. The patient will be included after checking inclusion criteria and signature of the informed consent form

Blood sampling (30 ml) will be performed before the initiation of the first line metastatic chemotherapy.

Detection of KRAS, NRAS et BRAF Mutations in Plasma Circulating DNA From Patients With Metastatic Colorectal Cancer

Multicenter Prospective Study Comparing KRAS, NRAS and BRAF Mutation Testing Using OncoBEAM Technique in Plasma vs Conventional Techniques in Formalin Fixed Paraffin Embedded Tissues

Compare the results of KRAS (exons 2, 3 et 4), NRAS (exons 2, 3 et 4) and BRAF (V600) genes genotyping using OncoBeam technique in blood samples with results achieved routinely by the molecular genetics platforms of the recruiting centers.

Institut de Cancérologie de Lorraine

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
OPTImal PALliative Anti-epidermal Growth Factor Receptor Treatment in Metastatic Colorectal Cancer -	NCT03750175	Colorectal Canc... Circulating Tum... KRAS Gene Mutat... NRAS Gene Mutat... BRAF Gene Mutat... Epidermal Growt...	Plasma circulat...	18 Years -	Aarhus University Hospital
NAUTILUS: OKI-179 Plus Binimetinib in Patients With Advanced Solid Tumors in the RAS Pathway (Phase 1b) and NRAS-mutated Melanoma (Phase 2)	NCT05340621	RAS Mutation NRAS Gene Mutat... Melanoma	OKI-179 + binim...	18 Years -	OnKure, Inc.
Expanded Access to Ulixertinib (BVD-523) in Patients With Advanced MAPK Pathway-Altered Malignancies	NCT04566393	Pancreatic Canc... Small Bowel Can... Colorectal Canc... Melanoma Non Small Cell ... Thyroid Cancer Bladder Cancer Head and Neck C... Gastric Cancer Esophageal Canc... Cholangiocarcin... Ovarian Cancer Hepatocellular ... Glioblastoma MAPK Gene Mutat... KRAS Activating... BRAF Gene Mutat... NRAS Gene Mutat... HRAS Gene Mutat... MEK Mutation ERK Mutation	Ulixertinib (BV...	12 Years -	xCures
OPTImal PALliative Anti-epidermal Growth Factor Receptor Treatment in Metastatic Colorectal Cancer -	NCT03750175	Colorectal Canc... Circulating Tum... KRAS Gene Mutat... NRAS Gene Mutat... BRAF Gene Mutat... Epidermal Growt...	Plasma circulat...	18 Years -	Aarhus University Hospital
Detection of KRAS, NRAS et BRAF Mutations in Plasma Circulating DNA From Patients With Metastatic Colorectal Cancer	NCT02751177	Colorectal Canc...	KRAS, NRAS et B...	18 Years -	Institut de Cancérologie de Lorraine

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