Caimi, Paolo F.

Abstract 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. Central tumor profiling was performed with an investigational next-generation DNA–targeted sequencing assay of alterations in 143 genes, and protein expression of protein expression of phosphatase and tensin homolog, mutL homolog 1, mutS homolog 2, and RB transcriptional corepressor 1. Treatments were allocated with a validated computational platform (MATCHBOX). A preplanned interim analysis evaluated assumptions and feasibility in this novel trial. Results At interim analysis, accrual was robust, tumor biopsies were safe (<1% severe events), and profiling success was 87.3%. Actionable molecular alteration frequency met expectations, but assignment and enrollment lagged due to histology exclusions and mismatch of resources to demand. To address this lag, we revised estimates of mutation frequencies, increased screening sample size, added treatments, and improved assay throughput and efficiency (93.9% completion and 14-day turnaround). Conclusions The experiences in the design and implementation of the NCI-MATCH trial suggest that profiling from fresh tumor biopsies and assigning treatment can be performed efficiently in a large national network trial. The success of such trials necessitates a broad screening approach and many treatment options easily accessible to patients.

Abstract Background Long-term outcomes from autologous stem cell transplant (ASCT) in patients (pts) with relapsed/refractory (R/R) Hodgkin lymphoma (HL) are significantly better in patients who achieve a complete remission (CR) from salvage chemotherapy prior to ASCT. However, standard salvage therapy produces variable CR rates (19%-60%) and is associated with significant toxicity. Brentuximab vedotin and bendamustine are highly active when administered as single agents to pts with R/R HL (34% and 33% CR rates, respectively) and have manageable safety profiles. This phase 1/2, single-arm, 2-stage, open-label study was designed to evaluate the safety and efficacy of brentuximab vedotin in combination with bendamustine for the treatment of pts with primary refractory disease or in first relapse (ClinicalTrials.gov #NCT01874054). Methods Pts received an outpatient IV infusion of 1.8 mg/kg brentuximab vedotin on Day 1 with bendamustine on Days 1 and 2 of 3-week cycles for up to 6 cycles. Pts could undergo ASCT any time after Cycle 2 and post-transplant resume treatment with brentuximab vedotin as monotherapy for up to 16 total doses. Phase 1 was designed to determine the recommended dose of bendamustine, with an initial dose of 90 mg/m2 and a de-escalation scheme to be implemented if it exceeded the maximum tolerated dose. During phase 2, bendamustine was administered at the recommended dose in order to assess the CR rate of the combination. Response was assessed by the investigator per Cheson 2007. Enrollment is complete and long-term follow-up for PFS and OS continues. Results Fifty-five pts (56% female) with a median age of 36 yrs (range, 19-79) were enrolled. Fifty-one percent of pts had relapsed disease and 49% of pts had primary refractory disease after frontline therapy. A median of 13.8 mos (range, 3-98) had elapsed since initial diagnosis. No dose-limiting toxicities were observed in the safety cohort, thus the recommended dose of bendamustine in combination with brentuximab vedotin was 90 mg/m2. Pts received a median of 2 cycles (range, 1-6) of the combination and a median of 9 cycles (range, 1-14) of single-agent brentuximab vedotin. The main toxicity observed with the combination was infusion-related reactions (56% overall). The most common symptoms (≥10%) were pyrexia (26%), chills (20%), dyspnea and nausea (15% each), flushing (13%), and hypotension (11%). Premedication with corticosteroids and antihistamines was instituted with a protocol amendment and appeared effective. Before the amendment, 6 pts (24% of treated pts) discontinued treatment prematurely because of IRRs; post-amendment, IRRs led to treatment discontinuation for 2 pts (7%). The CR rate of the combination was 74% (39/53 pts evaluable for response) and the overall objective response rate (CR and partial remission) was 93% (49/53 pts). The CR rate was 64% and 84% for refractory and relapsed pts, respectively. Stem cell collection after first-line mobilization (G-CSF± plerixafor) was successful in 93% of pts (37/40). Median number of CD34+ cells collected was 4.1 x106 (Q1, Q3: 3.0, 5.4) in a median of 2 (range, 1-5) apheresis sessions. Median time to neutrophil and platelet engraftment was 11 days (range, 9-21) and 13 days (range, 9-39), respectively. Pts have been followed for a median of approximately 1 year from first dose (median = 418 days; range, 118-635) and approximately 10 mos (314 days; range, 13-553) from ASCT. To date, 12 progression events have been observed: 7 in the 40 pts who underwent transplant and 5 in the 13 pts who did not undergo transplant. The estimated 12-mos PFS is 80% for both the transplanted population (95% CI: 70%, 90%) and the overall population (95% CI: 60%, 90%). Three of the 12 progression events were deaths; 2 pts died from progression of their HL and 1 pt died from septic shock after transplant. Conclusions The outpatient regimen of brentuximab vedotin 1.8 mg/kg on Day 1 in combination with bendamustine 90 mg/m2 on Days 1 and 2 of 3-week cycles induced a very high CR rate that compares favorably with historical data. The regimen has a manageable safety profile, with the most significant side effect being IRRs that can be successfully managed by premedication. The estimated 12-mos PFS rate of 80% demonstrates response durability, making the combination a promising salvage regimen for pts with HL in the first relapse setting. Progression-Free Survival Figure 1. Figure 1. Disclosures Off Label Use: Brentuximab vedotin is indicated in the US for treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates and for the treatment of patients with systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen. This study evaluates brentuximab vedotin in HL patients with primary refractory disease or in first relapse. . Sawas:Seattle Genetics, Inc.: Research Funding. Agura:Seattle Genetics, Inc.: Research Funding. Matous:Takeda Pharmaceuticals International Co.: Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Seattle Genetics, Inc.: Research Funding, Speakers Bureau. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding. Crosswell:KIYATEC (employment); Gilead (common stock ownership and research funding): Employment, Equity Ownership, Research Funding. Islas-Ohlmayer:Seattle Genetics, Inc.: Research Funding. Behler:Seattle Genetics, Inc.: Research Funding; Onyx Pharmaceuticals: Speakers Bureau. Cheung:Seattle Genetics, Inc.: Research Funding. Forero-Torres:Seattle Genetics, Inc.: Research Funding. Vose:Seattle Genetics, Inc.: Honoraria, Research Funding. Josephson:Seattle Genetics, Inc.: Employment, Equity Ownership. Advani:Seattle Genetics, Inc.: Research Funding; Genetech: Consultancy.

Abstract Background: Bendamustine and rituximab (BR) is a commonly chosen frontline treatment for grade 1-2 (G 1-2) follicular lymphoma (FL). This regimen resulted in significantly longer progression-free survival (PFS) and less toxicity compared to R-CHOP in the STiL trial [Rummel et al., 2013] and similar results were observed when comparing BR vs. R-CHOP/R-CVP in the confirmatory BRIGHT trial [Flinn et al., 2014, updated ASCO 2017]. Importantly, patients (pts) with grade 3A (G 3A) FL were excluded from these studies, yet the conclusions are often extrapolated to the treatment of G 3A pts. Notably, G 3A pts were included in the GALLIUM trial which used both bendamustine as well as CHOP backbones. Several retrospective studies of FL pts treated with frontline R-CHOP have demonstrated equivalent or improved overall survival (OS) for G 3A relative to G 1-2 FL (Koch et al., 2016, Mustafa et al., 2017, Yuan et al., 2017, Maeshima et al., 2013). Early disease progression after diagnosis and treatment with frontline R-CHOP has been identified as a strong predictor of poor OS in FL pts [Casulo et al. 2015], but has not been assessed in pts treated with frontline BR. We retrospectively evaluated outcomes of a large cohort of FL pts treated with frontline BR and stratified the results based on histologic grade and early vs. late progression. Methods: We reviewed medical records of adult (age >18) pts with FL treated with frontline BR at 18 US cancer centers. There was no central pathology review; each academic institution confirmed the diagnosis and grade of FL. Pts with unknown grade, grade 3B, or cutaneous FL were excluded. Baseline characteristics between grades were evaluated with the Chi-Square test for categorical variables and the Mann-Whitney U for continuous variables. Outcomes were calculated from time of initiation of BR. Patients were grouped according to whether or not they had progression of disease within 24 months of BR initiation (POD24). OS and PFS were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: 687 pts were included (616 G 1-2, 71 G 3A). Median age at diagnosis was 60 years (range 21-94) with 53% men. The median time from diagnosis to treatment with BR was 1 month (range 0-139). The median duration of follow up for the entire cohort was 39 months. Characteristics including age, gender, ethnicity, ECOG, stage, LDH, and FLIPI are shown in the Table, and did not significantly differ between G 1-2 and G 3A pts. Rates of complete response (CR) and partial response (PR) to BR were similar between G 1-2 and G 3A (72%/22% vs. 66%/21%, respectively, p=0.114) but progressive disease (PD) was higher in G 3A pts (11.9%) relative to G 1-2 (4.8%, p=0.025). As shown in the Figure (A and B), 3-year PFS and OS was significantly longer for G 1-2 vs. G 3A pts (75% vs. 65%, log rank p= 0.035 and 90% vs. 86%, log rank p=0.007, respectively). Seventy-six (12.3%) of the 616 G 1-2 pts and 13 (18.3%) of the 71 G 3A pts experienced POD24 (p=0.19). For pts with both G 1-2 and G 3A FL, POD24 was associated with inferior OS (3-year OS 95% vs. 57% for G 1-2 pts, log rank p<0.0001 and 3-year OS 93% vs. 37% for G 3A pts, log rank p<0.0001) compared to patients without POD24. Conclusions: G 3A FL pts have an inferior OS and are significantly more likely to have PD to frontline BR compared to G 1-2, which differs from the published experience with R-CHOP. Similar to outcomes after frontline treatment with R-CHOP, POD24 after frontline BR for FL is associated with very poor OS. Future studies are needed to address optimal frontline management of pts with G3A as well as for pts with any grade FL with POD24 after frontline BR. Disclosures Nastoupil: Novartis: Honoraria; Genentech: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; TG Therappeutics: Research Funding; Karus: Research Funding; Merck: Honoraria, Research Funding; Spectrum: Honoraria; Janssen: Research Funding; Juno: Honoraria. Cerhan:Jannsen: Other: Scientific Advisory Board; Celgene: Research Funding; Nanostring: Research Funding. Maurer:Celgene: Research Funding; Nanostring: Research Funding; Morphosys: Research Funding. Smith:Genentech: Research Funding; Incyte Corporation: Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Merck Sharp and Dohme Corp.: Consultancy, Research Funding; Acerta Pharma BV: Research Funding; Seattle Genetics: Research Funding. Lossos:Affimed: Research Funding. Portell:TG therapeutics: Research Funding; Amgen: Consultancy; Kite: Research Funding; AbbVie: Research Funding; BeiGene: Research Funding; Acerta: Research Funding; Genentech/Roche: Consultancy, Research Funding; Infinity: Research Funding. Calzada:Seattle Genetics: Research Funding. Cohen:Bristol-Myers Squibb: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; BioInvent: Consultancy. Ghosh:Spectrum: Consultancy; SGN: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics, an Abbvie Company: Consultancy, Research Funding, Speakers Bureau; TG Therapeutics: Honoraria, Research Funding; Celgene: Consultancy; Juno: Consultancy, Research Funding; Abbvie: Consultancy, Speakers Bureau; Genentech: Research Funding; F. Hoffman-La Roche Ltd: Research Funding; PCYC: Consultancy, Research Funding, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Forty seven Inc: Research Funding. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Merck, Takeda, Celgene, Seattle Genetics, Bayer: Research Funding. Caimi:Kite Pharma: Other: Advisory Board Participation; Genentech: Other: Advisory Board PArticipation, Research Funding; Celgene: Speakers Bureau; Kite Pharma: Other: Advisory Board Participation. Danilov:Gilead Sciences: Consultancy, Research Funding; Aptose Biosciences: Research Funding; Bayer Oncology: Consultancy, Research Funding; Astra Zeneca: Consultancy; Genentech: Consultancy, Research Funding; Takeda Oncology: Research Funding; TG Therapeutics: Consultancy; Verastem: Consultancy, Research Funding. Martin:AstraZeneca: Consultancy; Seattle Genetics: Consultancy; Janssen: Consultancy; Kite: Consultancy; Gilead: Consultancy; Bayer: Consultancy. Kamdar:Seattle Genetics: Speakers Bureau; Genentech: Consultancy. Kahl:AstraZeneca: Consultancy; Acerta: Consultancy; Juno: Consultancy; CTI: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Seattle Genetics: Consultancy; Abbvie: Consultancy; Genentech: Consultancy; ADC Therapeutics: Consultancy. Hill:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Diffuse large B-cell lymphomas (DLBCLs) and follicular lymphoma (FL) are the most common subtypes of B-cell non-Hodgkin’s lymphomas in adults. Histologic transformation of FL to DLBCL (TFL) occurs in approximately 15% of patients and is generally associated with a poor clinical outcome. Phosphatidylinositol 3-kinase (PI3K) inhibitors have shown promising results in the treatment of relapsed/refractory FL. CAR T-cell therapy (axicabtagene ciloleucel and tisagenlecleucel) has emerged as a novel treatment option for relapsed/refractory DLBCL and TFL. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines for B-Cell Lymphomas regarding the treatment of TFL and relapsed/refractory FL and DLBCL.

PURPOSE Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score–weighted (PSW) analysis were performed. RESULTS Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.

SummaryBendamustine (B) with rituximab (R) is a standard frontline treatment for medically fit follicular lymphoma (FL) patients. The safety and efficacy of maintenance rituximab (MR) after BR induction has not been formally compared to observation for FL, resulting in disparate practice patterns. Prospective trials have shown benefit of MR after R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R‐CVP (rituximab, cyclophosphamide, vincristine, prednisone), yet recent data from the GALLIUM study comparing outcomes of patients treated with chemotherapy with R or obinutuzumab (G) showed higher than anticipated fatal adverse events with BR/BG. In order to assess the efficacy and tolerability of MR after BR, we retrospectively collected data on 640 newly diagnosed patients treated with FL. We found that patients who achieved partial remission (PR) after ≥4 cycles of BR had improved duration of response (DOR) with MR vs. no maintenance, whereas those in complete remission did not. These findings were confirmed in a validation cohort. In the entire study population, the known fatal adverse event rate after BR was 2·5% and did not significantly differ in those receiving MR versus no maintenance. [Correction added on 14 January 2019, after online publication: The preceding sentence has been corrected in this current version.] Within the limitations inherent to retrospective analysis, these data suggest that FL patients with a PR to BR experience prolongation of remission with MR with an acceptable safety profile.

Abstract Oncology has undergone major changes in systemic treatment options, from chemotherapy to antiangiogenic agents to tyrosine-kinase inhibitors to immunotherapy. Historically, a therapeutic agent is tested in separate trials as monotherapy or combined with investigational or approved agents/modalities, to determine antitumor activity in each histology based on the premise that each histology responds differently to the same treatment. This paradigm is time consuming and may or may not make use of molecular characterization to test each agent in each histology. However, with the expansion of biologic understanding and development of various biomarkers, e.g., estrogen receptor and Her 2 amplification, we move beyond the basic paradigm of general histology to one in which treatment is based upon molecular characteristics of the tumor. Examples of recent discoveries from this more modern paradigm are (1) multiple histologies sharing a common molecular profile and (2) a subset within a single histology having a given molecular characteristic. Various agents have been tested singularly in terms of molecular aberrations and histology, e.g., ALK inhibitors and NSCLC. However, with the rapid increase in the number of targeted agents in development, more facile and efficient clinical trial designs are needed. The National Cancer Institute (NCI) and ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) collaborated in designing the Molecular Analysis for Therapy Choice trial (NCI-MATCH or EAY131), the first large-scale signal-finding precision medicine oncology trial in the United States to incorporate centralized NGS testing to direct patients to parallel (nonrandomized) phase II treatment arms under a master protocol. The trial is being conducted by the NCI National Clinical Trials Network (NCTN), with ECOG-ACRIN leading the trial. More than 100 investigators from across the NCTN adult cancer-oriented member groups (Alliance for Clinical Trials in Oncology, ECOG-ACRIN, NRG Oncology, and SWOG) have worked collaboratively to design and lead what is currently 30 treatment arms (subprotocols), with more arms in development. Wide-scale NCTN investigator involvement ensures use of the latest knowledge to define the actionable mutations required for eligibility and to make evidence-based selections of experimental agents. In NCI-MATCH, patients are assigned treatment based on the genomic alterations found in their tumors through genomic sequencing and other tests at the time of initial enrollment for screening. Unlike other phase II trials, each arm is open to advanced solid tumors, lymphomas, or myeloma that share a set of molecular aberrations, not restricted to a single histology. This strategy accommodates and encourages enrollment of rare tumors for which there are often no standard treatments and limited clinical trial options. NCI-MATCH has 10-30 concurrent treatment arms available to patients at any given time, testing both investigational agents and FDA-approved drugs for new indications. Most treatment arms have an enrollment goal of 35 patients, with some arms that address tumor gene variants of higher prevalence expanded to 70 patients. Together, the NCTN and NCI Community Oncology Research Program provide infrastructure for many clinical sites (&gt;1100) to participate, providing ready access to physicians and patients; screening enrollment has occurred in all 50 states in the U.S, the District of Columbia, and Puerto Rico. A specific assay was developed for the trial (the MATCH assay), and a laboratory network was organized to rapidly process the tissue and efficiently interrogate for mutations. NCI and ECOG-ACRIN statisticians developed the analysis plan and are currently maintaining data that are closely monitored by safety experts for any adverse event signals. Lastly, a bioinformatics system (MATCHbox) was developed to coordinate molecular data collection and support rule-based decision-making based on those data. Because genomics in oncology is rapidly expanding and evolving, NCI-MATCH required flexibility to accommodate brisker screening accrual than anticipated, and adaptation to constantly emerging information about new drugs and new molecular alterations. The goal to sequence the tumors of 6,000 patients with NCI funding was achieved two years ahead of schedule, but that cohort was not sufficient to fill all the arms—in particular, those aimed at the most rarely occurring tumor gene aberrations. Currently, the goal for the trial is to complete the open treatment arms by allowing for designated commercial and academic laboratories to notify ordering physicians when genomic tests they ordered to guide clinical care indicate a potential eligibility to a NCI-MATCH arm with a rare variant and allow for enrollment to the relevant treatment subprotocol if the patient meets all subprotocol eligibility criteria. The tissue confirmation of the molecular abnormality on the MATCH assay by the central laboratories will be accomplished after subprotocol enrollment so that patient treatment will not be delayed for confirmation. A demonstration project is now under way to test the applicability of this approach and potentially develop common standards for future use. With tumor sequencing becoming a more and more common practice in oncology, this may allow patients with mutations of low prevalence to have investigational treatment options. NCI-MATCH is expanding its panel and definition of actionable mutations to allow greater flexibility to incorporate in real time new mutations supported with adequate levels of evidence. The valuable genomic and clinical outcome data collected in the trial will permit evaluation of efficacy of targeting certain actionable mutations with a specific agent. In addition, biospecimens are being collected to build a rich resource for conducting auxiliary biology studies that may answer questions about prevalence of mutations in the metastatic setting, prevalence of mutations in rare histologies, and resistance mechanisms of various targeted therapy. At this meeting, two abstracts will provide an overall trial update and present information about the prevalence of mismatch repair deficiency (dMMR) in the centrally screened population. Citation Format: Alice P. Chen, Peter J. O'Dwyer, Lyndsay Harris, Barbara A. Conley, Stanley R. Hamilton, Mickey Williams, Robert J. Gray, Shuli Li, Lisa M. McShane, Lawrence V. Rubinstein, Susanna I. Lee, Shaji Kumar, Edith P. Mitchell, James A. Zwiebel, Constantine A. Gatsonis, Lalitha K. Shankar, Paolo F. Caimi, Carlos L. Arteaga, A John Iafrate, Jeffrey Sklar, Richard F. Little, Keith T. Flaherty. NCI-MATCH: A new paradigm in the era of genomic oncology [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr PL03-01.