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Purpose: Chronic graft-versus-host disease (cGVHD) remains the major cause of late morbidity after allogeneic hematopoietic cell transplantation. Colony-stimulating factor 1 receptor (CSF-1R)-dependent macrophages promote cGVHD fibrosis, and their elimination in preclinical studies ameliorated cGVHD. Axatilimab is a humanized monoclonal antibody that inhibits CSF-1R signaling and restrains macrophage development., Patients and Methods: This phase I (phI)/phase II (phII) open-label study (ClinicalTrials.gov identifier: NCT03604692) evaluated safety, tolerability, and efficacy of axatilimab in patients age ≥ 6 years with active cGVHD after ≥ 2 prior systemic therapy lines. Primary objectives in phI were to identify the optimal biologic and recommended phII dose and in phII to evaluate the overall (complete and partial) response rate (ORR) at the start of treatment cycle 7., Results: Forty enrolled patients (17 phI; 23 phII) received at least one axatilimab dose. In phI, a dose of 3 mg/kg given once every 4 weeks met the optimal biologic dose definition. Two dose-limiting toxicities occurred at the 3 mg/kg dose given once every 2 weeks. At least one treatment-related adverse event (TRAE) was observed in 30 patients with grade ≥ 3 TRAEs in eight patients, the majority known on-target effects of CSF-1R inhibition. No cytomegalovirus reactivations occurred. With the 50% ORR at cycle 7 day 1, the phII cohort met the primary efficacy end point. Furthermore, the ORR in the first six cycles, an end point supporting regulatory approvals, was 82%. Responses were seen in all affected organs regardless of prior therapy. Fifty-eight percent of patients reported significant improvement in cGVHD-related symptoms using the Lee Symptom Scale. On-target activity of axatilimab was suggested by the decrease in skin CSF-1R-expressing macrophages., Conclusion: Targeting profibrotic macrophages with axatilimab is a therapeutically promising novel strategy with a favorable safety profile for refractory cGVHD., Competing Interests: Carrie L. KitkoConsulting or Advisory Role: Horizon TherapeuticsTravel, Accommodations, Expenses: Mallinckrodt Mukta AroraEmployment: AmgenStock and Other Ownership Interests: AmgenResearch Funding: Syndax (Inst), Kadmon (Inst), Pharmacyclics (Inst) Zachariah DeFilippConsulting or Advisory Role: Kadmon, Omeros, Incyte, MorphoSysResearch Funding: Incyte, REGiMMUNE, Taiho Oncology Mohammad Abu ZaidStock and Other Ownership Interests: Pieris PharmaceuticalsConsulting or Advisory Role: Syndax, Ossium HealthResearch Funding: Syndax (Inst), Pharmacyclics (Inst), Janssen (Inst), Incyte (Inst), AlloVir (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/1350343 Vedran RadojcicEmployment: Syndax Pharmaceuticals, IncStock and Other Ownership Interests: Syndax Pharmaceuticals, IncConsulting or Advisory Role: Regeneron, AllakosOpen Payments Link: https://openpaymentsdata.cms.gov/physician/114735 Courtney B. BettsOther Relationship: Akoya Biosciences Lisa M. CoussensEmployment: Oregon Health & Science University (OHSU)Honoraria: Lustgarten Foundation for Pancreatic Cancer Research, Syndax, Carisma Therapeutics, Verseau Therapeutics, Inc, Scientific Advisory Board, Zymeworks, CytomX Therapeutics, Inc, Kineta Inc, Starr Cancer Consortium, Therapeutics Working Group:, Susan G Komen Foundation, Komen Scholar, AACR: Cancer Immunology ResearchConsulting or Advisory Role: Cell Signaling Technologies, Pharmacyclics, CytomX Therapeutics, Carisma Therapeutics, Verseau Therapeutics, Zymeworks, Kineta, Inc, AbbVie, Shasqi Inc, HiberCell, Alkermes, AstraZeneca Partner of Choice Network, OHSU site leader:, Genenta Science, Susan G Komen Foundation, Komen Scholar, Syndax, PDX Pharmaceuticals, Inc, Pio Therapeutics Pty LtdResearch Funding: Syndax, Pharmacyclics, Cell Signaling Technologies, Innate Pharma, Acerta Pharma (Inst), Susan G. Komen for the Cure (Inst), ZellBio, Inc, HiberCellOther Relationship: Prospect Creek Foundation, Lustgarten Foundation for Pancreatic Cancer Research, (P30) Koch Institute for Integrated Cancer Research, Massachusetts Institute of Technology (2012-present; honorarium), (P30) Salk Institute Cancer Center (2016-2020; honorarium), Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (2016-present; honorarium), Dana Farber Cancer Center Breast SPORE (2017-present; honorarium), (P30) Dana Farber/Harvard Cancer Center (2019-present; honorarium), (P30) University of California, San Diego Moores Cancer Center (2019-present; honorarium), Cancer Research Institute (CRI; 2013-present; unpaid), The V Foundation for Cancer Research (2013-present; unpaid), Starr Cancer Consortium (2011-present, honorarium), Therapeutics Working Group (2019-present; paid), NIH/NCI-Frederick National Laboratory Advisory Committee (FNLAC; 2016-present; daily honorarium), Susan G Komen Foundation, Komen Scholar (2020-2023; honorarium), (P50) Dana Farber Cancer Center Breast SPORE, (P30) The Jackson Laboratory Cancer Center, (P01) Columbia University Medical Center, Prostate P01, (P50) MDACC GI SPORE, American Association for Cancer Research, AACR: Cancer Discovery, Cancer Cell, National Foundation for Cancer Research Michael L. MeyersEmployment: SyndaxLeadership: SyndaxStock and Other Ownership Interests: Syndax, Nuvalent, IncConsulting or Advisory Role: Syndax, Nuvalent, IncPatents, Royalties, Other Intellectual Property: Syndax, Nuvalent, Inc Peter OrdentlichEmployment: SyndaxLeadership: SyndaxStock and Other Ownership Interests: SyndaxConsulting or Advisory Role: Patrys, Twentyeight-Seven TherapeuticsPatents, Royalties, Other Intellectual Property: Issued patents and patents pending Christine QuarantoEmployment: Syndax, Aerovate TherapeuticsStock and Other Ownership Interests: Syndax Pharmaceuticals, Aerovate Therapeutics Aaron SchmittEmployment: Syndax Pharmaceuticals IncStock and Other Ownership Interests: Syndax Yu GuEmployment: Syndax, AstraZenecaStock and Other Ownership Interests: Syndax, AstraZeneca Bruce R. BlazarStock and Other Ownership Interests: BlueRock Therapeutics, Tmunity Therapeutics, Inc, Magenta TherapeuticsConsulting or Advisory Role: BlueRock Therapeutics, Magenta Therapeutics, Obsidian Therapeutics, Editas MedicineResearch Funding: BlueRock Therapeutics, Rheos Medicines, Équilibre Biopharmaceuticals Corp, Carisma TherapeuticsPatents, Royalties, Other Intellectual Property: Inducible regulatory T-cell generation for hematopoietic cell transplants (UMN Z09026), US 9,228,172, TALEN-based gene correction, Patent No. 9,393,257, Generation of natural killer cells and lymphoid tissue inducer–like (LTI-like) NK-22 cells, 9,862,928, Method for correcting a genetic sequence, 10,648,002Travel, Accommodations, Expenses: Incyte, Magenta Therapeutics, Rheos Medicines Amandeep SalhotraConsulting or Advisory Role: Kadmon, Syros Pharmaceuticals, SobiResearch Funding: Bristol Myers Squibb Iskra PusicConsulting or Advisory Role: Kadmon, Incyte, Syndax Madan JagasiaEmployment: Iovance BiotherapeuticsStock and Other Ownership Interests: Iovance BiotherapeuticsConsulting or Advisory Role: Kadmon Stephanie J. LeeHonoraria: Wolters Kluwer, PERConsulting or Advisory Role: EMD Serono, Pfizer, 4SC, Mallinckrodt/Therakos, Almirall Hermal GmbH, Rain Therapeutics, Kadmon, EquilliumResearch Funding: Kadmon, Amgen, Bristol Myers Squibb, EMD Serono, Incyte, Syndax, Pfizer, AstraZenecaPatents, Royalties, Other Intellectual Property: Patent pending for high-affinity T-cell receptors that target the Merkel polyomavirusOther Relationship: National Marrow Donor Program, Society for Investigative Dermatology (SID)No other potential conflicts of interest were reported.

Purpose: Despite recognition of both the growing cancer burden in low- and middle-income countries and the disproportionately high mortality rates in these settings, delivery of high-quality cancer care remains a challenge. The disparities in cancer care outcomes for many geographic regions result from barriers that are likely complex and understudied. This study describes the development and use of a streamlined needs assessment questionnaire (NAQ) to understand the barriers to providing quality cancer care, identifies areas for improvement, and formulates recommendations for implementation., Methods: Using a comprehensive NAQ, in-depth interviews were conducted with 17 hospital staff involved in cancer care at two teaching hospitals in Nigeria. Data were analyzed using content analysis and organized into a framework with preset codes and emergent codes, where applicable., Results: Data from the interviews were organized into six broad themes: staff, stuff, system, space, lack of palliative care, and provider bias, with key barriers within themes including: financial, infrastructural, lack of awareness, limited human capacity resources, lack of palliative care, and provider perspective on patient-related barriers to cancer care. Specific solutions based on ability to reasonably implement were subcategorized into short-, medium-, and long-term goals., Conclusion: This study provides a framework for a streamlined initial needs assessment and a unique discussion on the barriers to high-quality oncology care that are prevalent in resource-constrained settings. We report the feasibility of collecting and organizing data using a streamlined NAQ and provide a thorough and in-depth understanding of the challenges in this setting. Knowledge gained from the assessments will inform steps to improve oncology cancer in these settings.

Background: The highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers. In the current study, the authors describe the clinical course of children with locally advanced TRK fusion sarcoma who were treated preoperatively with larotrectinib and underwent subsequent surgical resection., Methods: A total of 24 children were treated on a pediatric phase 1 trial of larotrectinib (ClinicalTrials.gov identifier NCT02637687). Five children who had a documented TRK fusion sarcoma and underwent surgical resection were included in the current analysis. Tumor response (Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1) and surgical outcomes were collected prospectively., Results: A total of 5 patients (median age, 2 years; range, 0.4-12 years) had locally advanced infantile fibrosarcoma (3 patients) or soft-tissue sarcoma (2 patients). Four patients had disease that was refractory to standard therapy. All 5 patients achieved a partial response to larotrectinib by version 1.1 of RECIST and underwent surgical resection after a median of 6 cycles (range, 4-9 cycles) of treatment. Surgical resections were R0 (negative resection margins with no tumor at the inked resection margin) in 3 patients, R1 (microscopic residual tumor at the resection margin) in 1 patient, and R2 (macroscopic residual tumor at the resection margin) in 1 patient. Three patients achieved complete (2 patients) or near-complete (>98% treatment effect; 1 patient) pathologic responses. These patients remained in follow-up and were no longer receiving larotrectinib for a minimum of 7 to 15 months postoperatively. Two patients had viable tumor at the time of surgical resection and positive resection margins and continued to receive adjuvant larotrectinib. No patients experienced postoperative complications or wound healing issues., Conclusions: Children with locally advanced TRK fusion sarcomas may proceed to surgical resection after treatment with the selective TRK inhibitor larotrectinib, thereby sparing them the potentially significant morbidity noted with current approaches. These results support the evaluation of larotrectinib as presurgical therapy in children with newly diagnosed TRK fusion sarcomas., (© 2018 American Cancer Society.)