Publications by authors named "Barbara A Conley"
Purpose: The NCI-MATCH trial assigned patients with solid tumors, lymphomas, or multiple myeloma to targeted therapies on the basis of identified genetic alterations from tumor biopsies. In preclinical models, ()-inactivated tumors display sensitivity to focal adhesion kinase (FAK) inhibition. The EAY131-U subprotocol evaluated the efficacy of defactinib, a FAK inhibitor, in patients with -altered tumors.
View Article and Find Full Text PDFPurpose: The NCI-MATCH study is a tumor-agnostic platform trial enrolling patients to targeted therapies on the basis of genomic alterations. Subprotocol V investigated sunitinib in patients with tumors harboring - mutations.
Methods: EAY131-V, is an open-label, single-arm, phase II study.
Purpose: Amplification of CDK4 and CDK6 is a feature of a variety of malignancies, and preclinical evidence suggests inhibition of CDK4/6 is a plausible treatment strategy in these tumors. Subprotocol Z1C of the NCI-MATCH trial was designed to evaluate the CDK4/6 inhibitor palbociclib in CDK4- or CDK6-amplified tumors.
Patients And Methods: Patients had a solid malignancy with progression on at least one systemic therapy for advanced disease.
Purpose: National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) was a multicohort phase 2 trial that assigned patients with advanced pretreated cancers to molecularly targeted therapies on the basis of tumor genomic testing. NCI-MATCH Arm A evaluated afatinib, an EGFR tyrosine kinase inhibitor (TKI) approved for advanced non-small cell lung cancer, in patients with tumors other than lung cancer harboring mutations.
Methods: Patients with advanced pretreated cancers other than lung cancer found to have selected actionable mutations were offered participation in Arm A.
Purpose: Despite fibroblast growth factor receptor () inhibitors being approved in tumor types with select rearrangements or gene mutations, amplifications of represent the most common alteration across malignancies. Subprotocol K1 (EAY131-K1) of the National Cancer Institute-MATCH platform trial was designed to evaluate the antitumor efficacy of the oral inhibitor, erdafitinib, in patients with tumors harboring amplification.
Methods: EAY131-K1 was an open-label, single-arm, phase II study with central confirmation of presence of amplification in tumors.
Purpose: Subprotocol K2 (EAY131-K2) of the NCI-MATCH platform trial was an open-label, single-arm, phase II study designed to evaluate the antitumor efficacy of the oral FGFR1-4 inhibitor, erdafitinib, in patients with tumors harboring FGFR1-4 mutations or fusions.
Methods: Central confirmation of tumor FGFR1-4 mutations or fusions was required for outcome analysis. Patients with urothelial carcinoma were excluded.
Purpose: The National Cancer Institute Molecular Analysis for Therapy Choice trial is a signal-finding genomically driven platform trial that assigns patients with any advanced refractory solid tumor, lymphoma, or myeloma to targeted therapies on the basis of next-generation sequencing results. Subprotocol E evaluated osimertinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with mutations.
Methods: Eligible patients had mutations (T790M or rare activating) and received osimertinib 80 mg once daily.
Purpose: NCI-MATCH assigned patients with advanced cancer and progression on prior treatment, based on genomic alterations in pretreatment tumor tissue. Arm J (EAY131-J) evaluated the combination of trastuzumab/pertuzumab (HP) across HER2-amplified tumors.
Patients And Methods: Eligible patients had high levels of HER2 amplification [copy number (CN) ≥7] detected by central next-generation sequencing (NGS) or through NCI-designated laboratories.
The NCI-MATCH (Molecular Analysis for Therapy Choice) trial ( NCT02465060 ) was launched in 2015 as a genomically driven, signal-seeking precision medicine platform trial-largely for patients with treatment-refractory, malignant solid tumors. Having completed in 2023, it remains one of the largest tumor-agnostic, precision oncology trials undertaken to date. Nearly 6,000 patients underwent screening and molecular testing, with a total of 1,593 patients (inclusive of continued accrual from standard next-generation sequencing) being assigned to one of 38 substudies.
View Article and Find Full Text PDFPurpose: NCI-MATCH is a precision medicine trial using genomic testing to allocate patients with advanced malignancies to targeted treatment subprotocols. This report combines two subprotocols evaluating trametinib, a MEK1/2 inhibitor, in patients with ([S1] or [S2]) altered tumors.
Methods: Eligible patients had tumors with deleterious inactivating or mutations by the customized Oncomine AmpliSeq panel.
Purpose: Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, the gene encoding cyclin D, is known to be amplified in a variety of solid tumors. Palbociclib is an oral CDK4/6 inhibitor, approved in advanced breast cancer in combination with endocrine therapy.
View Article and Find Full Text PDFIntroduction: The Exceptional Responders Initiative (ERI) at the National Cancer Institute attempts to correlate unusually good outcomes in patients with cancer with genetic targets in tumors and the therapies the patients received. It is not known if other factors might contribute to exceptional responses or outcomes. We explored aspects of the medical history, lifestyle changes, complementary and alternative medicine (CAM) use and communication between health care practitioners and patients who experienced an exceptional response following cancer treatment.
View Article and Find Full Text PDFPurpose: National Cancer Institute-Molecular Analysis for Therapy Choice is a multicohort trial that assigns patients with advanced cancers to targeted therapies on the basis of central tumor genomic testing. Arm B evaluated afatinib, an ErbB family tyrosine kinase inhibitor, in patients with -activating mutations.
Methods: Eligible patients had selected single-nucleotide variants or insertions/deletions detected by the National Cancer Institute-Molecular Analysis for Therapy Choice next-generation sequencing assay.
Purpose: mutations frequently contribute to oncogenesis in solid tumors. Taselisib, a potent and selective inhibitor of phosphoinositide 3-kinase, has demonstrated clinical activity in -mutant breast cancer. Whether mutations predict sensitivity to taselisib in other cancer types is unknown.
View Article and Find Full Text PDFPurpose: Activating mutations in are observed across multiple tumor types. The NCI-MATCH (EAY131) is a tumor-agnostic platform trial that enrolls patients to targeted therapies on the basis of matching genomic alterations. Arm Z1F evaluated copanlisib, an α and δ isoform-specific phosphoinositide 3-kinase (PI3K) inhibitor, in patients with mutations (with or without loss).
View Article and Find Full Text PDFPurpose: Preclinical and clinical data suggest that downstream inhibition with an MEK inhibitor, such as binimetinib, might be efficacious for -mutated cancers.
Patients And Methods: Patients enrolled in the NCI-MATCH trial master protocol underwent tumor biopsy and molecular profiling by targeted next-generation sequencing. Patients with -mutated tumors, except melanoma, were enrolled in subprotocol Z1A, a single-arm study evaluating binimetinib 45 mg twice daily.
Article Synopsis
- - The NCI-MATCH trial investigated the effectiveness of the drug capivasertib in patients with AKT1 E17K-mutated metastatic tumors, specifically focusing on its objective response rate (ORR).
- - A total of 35 patients were studied, primarily women with a median age of 61, and the most common cancer types among them were breast and gynecologic cancers.
- - The study found that the ORR for capivasertib was 28.6%, indicating a partial or complete response in a portion of the patients treated.
A small fraction of cancer patients with advanced disease survive significantly longer than patients with clinically comparable tumors. Molecular mechanisms for exceptional responses to therapy have been identified by genomic analysis of tumor biopsies from individual patients. Here, we analyzed tumor biopsies from an unbiased cohort of 111 exceptional responder patients using multiple platforms to profile genetic and epigenetic aberrations as well as the tumor microenvironment.
View Article and Find Full Text PDFPurpose: Therapeutically actionable molecular alterations are widely distributed across cancer types. The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial was designed to evaluate targeted therapy antitumor activity in underexplored cancer types. Tumor biopsy specimens were analyzed centrally with next-generation sequencing (NGS) in a master screening protocol.
View Article and Find Full Text PDFPurpose: mutations are commonly found in melanoma and thyroid cancers and to a lesser degree in other tumor types. Subprotocol H (EAY131-H) of the NCI-MATCH platform trial sought to investigate the selective BRAF inhibitor dabrafenib and the MEK1/2 inhibitor trametinib in patients with solid tumors, lymphomas, or multiple myeloma whose tumors harbored a mutation.
Patients And Methods: EAY131-H is an open-label, single-arm study.
Purpose: NCI-MATCH is a nationwide, histology-agnostic, signal-finding, molecular profile-driven trial for patients with refractory cancers, lymphomas, or myelomas. Patients with tumors harboring actionable aberration(s) in fibroblast growth factor receptor () were treated with AZD4547, an oral FGFR1-3 inhibitor.
Methods: Patients' tumors were screened by next-generation sequencing for predefined amplification, activating mutations, or fusions.
Background: Tumor molecular profiling from patients experiencing exceptional responses to systemic therapy may provide insights into cancer biology and improve treatment tailoring. This pilot study evaluates the feasibility of identifying exceptional responders retrospectively, obtaining pre-exceptional response treatment tumor tissues, and analyzing them with state-of-the-art molecular analysis tools to identify potential molecular explanations for responses.
Methods: Exceptional response was defined as partial (PR) or complete (CR) response to a systemic treatment with population PR or CR rate less than 10% or an unusually long response (eg, duration >3 times published median).
Purpose: Substantial preclinical evidence and case reports suggest that MEK inhibition is an active approach in tumors with mutations outside the V600 locus, and in fusions. Thus, Subprotocol R of the NCI-MATCH study tested the MEK inhibitor trametinib in this population.
Patients And Methods: The NCI-MATCH study performed genomic profiling on tumor samples from patients with solid tumors and lymphomas progressing on standard therapies or with no standard treatments.
Background: The proportion of tumors of various histologies that may respond to drugs targeted to molecular alterations is unknown. NCI-MATCH, a collaboration between ECOG-ACRIN Cancer Research Group and the National Cancer Institute, was initiated to find efficacy signals by matching patients with refractory malignancies to treatment targeted to potential tumor molecular drivers regardless of cancer histology.
Methods: Trial development required assumptions about molecular target prevalence, accrual rates, treatment eligibility, and enrollment rates as well as consideration of logistical requirements.
Purpose: The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial, the largest national precision oncology study to date (> 1,100 sites) of patients with relapsed or refractory malignancies, assigned patients to targeted therapy in parallel phase II studies based on tumor molecular alterations. The anti-programmed death receptor 1 inhibitor nivolumab previously showed activity in mismatch repair (MMR)-deficient colon cancer. We hypothesized that nivolumab would have activity in patients with MMR-deficient, noncolorectal tumors.
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