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Objective: The aim of this study was to assess the seroconversion rate and percent inhibition of neutralizing antibodies against the wild-type and Omicron variants of SARS-CoV-2 in patients with solid cancer who received two COVID-19 vaccine doses by comparing chemotherapy and nonchemotherapy groups., Methods: This prospective cohort study enrolled 115 cancer patients from Maharaj Nakorn Chiang Mai Hospital, Sriphat Medical Center, Faculty of Medicine, Chiang Mai University, and Chiang Mai Klaimor Hospital, Chiang Mai, Thailand, between August 2021 and February 2022, with data from 91 patients who received two COVID-19 vaccine doses analyzed. Participants received vaccines as part of their personal vaccination programs, including various mRNA and non-mRNA vaccine combinations. Blood samples were collected at baseline, on day 28, and at 6 months post-second dose to assess neutralizing antibodies. The primary outcome was the seroconversion rate against the wild-type and Omicron variants on day 28. Secondary outcomes included seroconversion at 6 months, factors associated with seroconversion, and safety., Results: Among the participants, 45% were receiving chemotherapy. On day 28, seroconversion rates were 77% and 62% for the wild-type and Omicron variants, respectively. Chemotherapy did not significantly affect seroconversion rates (p = 0.789 for wild type, p = 0.597 for Omicron). The vaccine type administered was positively correlated with seroconversion, with an adjusted odds ratio (95% confidence interval) of 25.86 (1.39-478.06) for the wild type and 17.38 (3.65-82.66) for the Omicron variant with the primary heterologous vaccine regimen. Grades 1 and 2 adverse events were observed in 34.0% and 19.7% of participants, respectively., Conclusions: Despite the lower seroconversion rate against the Omicron variant, no significant difference was observed between the chemotherapy and nonchemotherapy groups. COVID-19 vaccinations demonstrated good tolerability in this cohort. These findings highlight the importance of vaccine safety and immunogenicity in cancer patients and can inform tailored vaccination strategies for this vulnerable population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chewaskulyong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background/Objectives : The prolonged time to reach investigation and management decisions in non-small cell lung cancer (NSCLC) patients can negatively impact long-term outcomes. This retrospective cohort study aims to assess the impact of a multidisciplinary team conference (MDT) on NSCLC care quality and outcomes. Methods : This retrospective study included resectable NSCLC patients who underwent pulmonary resection at Chiang Mai University Hospital, Thailand, from 1 January 2009 to 31 December 2021. Patients were divided into two groups: non-MDT and MDT groups, based on the initiation of MDT on 1 March 2018. The study compared overall survival, disease-free survival, and waiting times for investigation and surgery between the two groups. The effect of MDT on these outcomes was analyzed using multivariable analysis with inverse-probability weighting propensity scores. Results : The study included 859 patients, with 583 in the non-MDT group and 276 in the MDT group. MDT groups had a higher proportion of stage I and II NSCLC patients undergoing pulmonary resection (78.6% vs. 59.69%, p < 0.001). In multivariable analysis, patients in the MDT group had a significantly higher likelihood of longer survival compared to the non-MDT group (adjusted HR 0.23, 95% CI 0.09-0.55). Median waiting times for bronchoscopy (3 days vs. 12 days, p = 0.012), pathologic report (7 days vs. 13 days, p < 0.001), and surgery scheduling (18 days vs. 25 days, p = 0.001) were significantly shorter in the MDT group. Conclusions : An MDT has a survival benefit in NSCLC care and improves waiting times for investigation and treatment steps. Further studies are needed to validate these results.

Background: Malnutrition harms treatment outcomes, QoL, and survival in lung cancer patients. Effective dietary counseling can improve nutrition, but few randomized controlled trials have focused on lung cancer patients. The objective of this study was to determine if dietary counseling improves nutritional and treatment outcomes when compared to routine care. Methods : This open-label parallel RCT was conducted at Maharaj Nakorn Chiang Mai Hospital in Thailand. The investigators used computer-generated blocked randomization to assign patients to dietary counseling by a nutritionist or routine care. The nutritionist sessions occurred before treatment, with follow-ups at 3-4 weeks and 12 weeks. The primary outcome was the mean percentage change in the body weight of patients at 12 weeks. Secondary outcomes included changes in the BMI, nutrition score, QoL, serum albumin level, lymphocyte count, energy and protein intake, treatment response, PFS, and OS. Results : Between April 2020 and May 2022, after completing recruitment, 80 lung cancer patients were randomized: 43 to dietary counseling and 37 to routine care. The dietary counseling group showed significant benefits, with smaller decreases in body weight at 3-4 weeks (-0.8% vs. -2.6%, p = 0.05) and 12 weeks (-1.1% vs. -4.3%, p = 0.05). They also had higher energy and protein intake levels and better treatment response rates. The secondary outcomes and significant adverse events did not differ significantly between the groups. Conclusions : Dietary counseling helps to maintain body weight, maintain dietary intake, and enhance treatment responses in lung cancer patients. Although not all nutritional markers or survival outcomes were affected, these findings highlight the importance of early nutritional interventions.

Background: In the preplanned interim analysis of the TOPAZ-1 study, durvalumab plus gemcitabine-cisplatin significantly improved overall survival versus placebo plus gemcitabine-cisplatin in participants with advanced biliary tract cancer. We aimed to report updated overall survival and safety data from TOPAZ-1 with additional follow-up and data maturity beyond the interim analysis., Methods: TOPAZ-1 was a phase 3, randomised, double-masked, placebo-controlled, global study done at 105 sites in 17 countries. Participants aged 18 years or older with unresectable, locally advanced, or metastatic biliary tract cancer were randomly assigned (1:1) to durvalumab plus gemcitabine-cisplatin or placebo plus gemcitabine-cisplatin using a computer-generated randomisation scheme, stratified by disease status and primary tumour location. Participants received durvalumab (1500 mg) or placebo on day 1 of each cycle every 3 weeks for up to eight cycles, plus gemcitabine (1000 mg/m 2 ) and cisplatin (25 mg/m 2 ) intravenously on days 1 and 8 of each cycle every 3 weeks for up to eight cycles, followed by durvalumab (1500 mg) or placebo monotherapy every 4 weeks until disease progression or other discontinuation criteria were met. Investigators and participants were masked to study treatment. The primary endpoint was overall survival. TOPAZ-1 met its primary endpoint at the preplanned interim analysis, and the study is active but no longer recruiting participants. Updated overall survival and safety data from TOPAZ-1, with additional follow-up (data cutoff Feb 25, 2022) and data maturity beyond the interim analysis, are reported here. Efficacy was assessed in the full analysis set (all randomly assigned participants). Safety was assessed in the safety analysis set (all participants who received at least one dose of study treatment). The TOPAZ-1 study is registered with ClinicalTrials.gov, NCT03875235., Findings: From April 16, 2019, to Dec 11, 2020, 914 participants were enrolled, 685 of whom were randomly assigned (341 to the durvalumab plus gemcitabine-cisplatin group and 344 to the placebo plus gemcitabine-cisplatin group). 345 (50%) participants were male and 340 (50%) were female. Median follow-up at the updated data cutoff was 23·4 months (95% CI 20·6-25·2) in the durvalumab plus gemcitabine-cisplatin group and 22·4 months (21·4-23·8) in the placebo plus gemcitabine-cisplatin group. At the updated data cutoff, 248 (73%) participants in the durvalumab plus gemcitabine-cisplatin group and 279 (81%) participants in the placebo plus gemcitabine-cisplatin group had died (median overall survival 12·9 months [95% CI 11·6-14·1] vs 11·3 months [10·1-12·5]; hazard ratio 0·76 [95% CI 0·64-0·91]). Kaplan-Meier-estimated 24-month overall survival rates were 23·6% (95% CI 18·7-28·9) in the durvalumab plus gemcitabine-cisplatin group and 11·5% (7·6-16·2) in the placebo plus gemcitabine-cisplatin group. Maximum grade 3 or 4 adverse events occurred in 250 (74%) of 338 participants in the durvalumab plus gemcitabine-cisplatin group and 257 (75%) of 342 in the placebo plus gemcitabine-cisplatin group. The most common maximum grade 3 or 4 treatment-related adverse events were decreased neutrophil count (70 [21%] vs 86 [25%]), anaemia (64 [19%] vs 64 [19%]), and neutropenia (63 [19%] vs 68 [20%])., Interpretation: Durvalumab plus gemcitabine-cisplatin showed robust and sustained overall survival benefit with no new safety signals. Findings continue to support the regimen as a standard of care for people with untreated, advanced biliary tract cancer., Funding: AstraZeneca., Competing Interests: Declaration of interests D-YO reports advisory fees from Arcus Biosciences, Aslan Pharmaceuticals, AstraZeneca, Basilea, Bayer, BeiGene, Bristol Myers Squibb/Celgene, Genentech/Roche, Halozyme, IQVIA, Merck Serono, Novartis, Taiho Pharmaceutical, Turning Point Therapeutics, Yuhan, and Zymeworks; and institutional research funding from Array BioPharma, AstraZeneca, BeiGene, Eli Lilly, Handok, MSD, Novartis, and Servier. ARH reports consulting fees from AstraZeneca, Bristol Myers Squibb, and Genentech/Roche; research funding from Genentech and Merck; and speakers bureau fees from Eisai and Bristol Myers Squibb. MB reports consulting fees from AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Ipsen, MSD, Roche, and Sirtex Medical; speakers bureau fees from Bayer, Eisai, and Roche; and support for travel and attending meetings from AstraZeneca, Bayer, and Sirtex Medical. TO reports advisory fees from AstraZeneca, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Incyte, Meiji Seika Pharma, Mundipharma, Nihon Servier, Nippon Shinyaku, Pfizer, Taiho Pharmaceutical, and Takara Bio; and speaker fees from AstraZeneca, Baxter, Bayer, Bristol Myers Squibb, Chugai Pharma, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, MSD, Nihon Servier, Novartis, Ono Pharmaceutical, Taiho Pharmaceutical, Teijin Pharma, and Yakult Honsha. L-TC reports personal speaker fees from Bristol Myers Squibb, CStone, Eli Lilly, Ipsen, Ono Pharmaceutical, Novartis, PharmaEngine, and TTY; fees for medical monitoring for clinical trials for Taivex; fees received as a data and safety monitoring committee member for clinical trials for OBI Pharma; advisory fees from AstraZeneca, MSD, and SynCoreBio; speaker fees from AstraZeneca, HuniLife Biotechnology, Ono Pharmaceutical, ScinoPharm Taiwan, SynCoreBio, and TTY; and research funding from Celgene. MK reports research funding from AbbVie and Takeda; and honoraria from EA Pharma and AstraZeneca. JWK reports research funding from inno.N and Jeil Pharmaceutical; and consulting fees from AstraZeneca, BeiGene, BeyondBio, Bristol Myers Squibb/Celgene, Eisai, GC Cell, MSD Ono, Sanofi-Aventis, Servier, and TCUBEit. TS reports speaker fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Baxter, Eli Lilly, Mundipharma (Thailand), Janssen, MSD, Novartis, Roche, and Takeda; and advisory fees from Novartis and Roche. MI reports grant or research support from Aslan Pharmaceuticals, AstraZeneca, Bayer, Bristol Myers Squibb, Chiome Bioscience, Chugai Pharma, Delta-Fly Pharma, EA Pharma, Eisai, Eli Lilly Japan, J-Pharma, Merck, Merus NV, Nihon Servier, Novartis, Ono Pharmaceutical, Pfizer, Takeda, and Yakult; fees or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Astellas Pharma, Bayer, Bristol Myers Squibb, Chugai Pharma, Eisai, Eli Lilly Japan, MSD, Nihon Servier, Novartis, Otsuka, Dainippon Sumitomo Pharma, Taiho Pharmaceutical, Takeda, Teijin Pharma, and Yakult; and fees for participation on a data safety monitoring board or advisory board from Aslan Pharmaceuticals, Bayer, Bristol Myers Squibb, Chugai Pharma, Eisai, Eli Lilly Japan, GlaxoSmithKline, Nihon Servier, Novartis, and Takeda. J-SC reports grant or research support from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Janssen, Eli Lilly, Merck KGaA, MSD, MSD Oncology, Oncologie, Ono Pharmaceutical, Roche, Senhwa Biosciences, SynCore, and TTY; and consulting fees from Ono Pharmaceutical. PP reports personal fees for an advisory board from AstraZeneca, Sanofi-Aventis, Bristol Myers Squibb, Janssen Oncology, MSD, Pierre Fabre, Roche, and Servier; personal fees as an invited speaker from AstraZeneca, Ipsen, Pierre Fabre, and Merck; and being a principal investigator for AstraZeneca and Roche. HAB reports research funding from AbbVie, Agios, Arch Pharmalabs, ARMO BioSciences, Array BioPharma, Arvinas, AstraZeneca, Bayer, BIND Therapeutics, BioAtla, BioMed Valley Discoveries, Biotheryx, Boehringer Ingelheim, Bristol Myers Squibb, CALGB, CicloMed, Coordination Pharmaceuticals, CytomX, eFFECTOR Therapeutics, Eli Lilly, EMD Serono, Foundation Medicine, Gossamer Bio, Gilead Sciences, GlaxoSmithKline, Harpoon Therapeutics, Incyte, Infinity Pharmaceuticals, Janssen, Jiangsu Hengrui Pharmaceuticals, Jounce Therapeutics, Kymab, MacroGenics, MedImmune, Merck, Millennium/Takeda, miRNA Therapeutics, Moderna, NGM Bio, Novartis, Pfizer, Revolution Medicine, Roche/Genentech, Ryvu Therapeutics, Seattle Genetics, Tesaro, TG Therapeutics, Verastem Oncology, Vertex Pharmaceuticals, XBiotech, and Zymeworks; and consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Forma Therapeutics, Grail, Incyte, Novartis, Pfizer, and Vincerx Pharma. VO reports grant or research support from Dr Reddy's Laboratories and Zydus Cadila; institutional fees for advisory board participation from AstraZeneca, Panacea Biotec, Dr Reddy's Laboratories, and Zydus Cadila; travel reimbursement as an invited speaker from AstraZeneca; other institutional financial interests with Alkem Laboratories, Eisai, Intas Pharmaceuticals, and Micro Labs; and non-financial interests with the Indian Association of Supportive Care in Cancer. ST reports honoraria from AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, MSD, Novartis, and Roche; speaker fees from Bristol Myers Squibb, Ipsen, and Novartis; and non-financial interests with AstraZeneca, Bristol Myers Squibb, Ipsen, Janssen, and Roche. CM reports institutional grant or research support from AstraZeneca, Daiichi Sankyo, Eisai, J-Pharma, Hitachi, Merck BioReliance, MSD, Kyowa Kirin, Ono Pharmaceutical, Taiho Pharmaceutical, and Yakult Honsha; personal fees for advisory board participation from AstraZeneca, Boehringer Ingelheim, Merck BioReliance, MSD, Servier, Taiho Pharmaceutical, and Yakult; and personal fees received as an invited speaker from AstraZeneca, Eisai, Kyowa Kirin, MSD, Novartis, Servier, Taiho Pharmaceutical, Teijin Pharma, and Yakult Honsha. REZ reports speaker fees from Bristol Myers Squibb, Ipsen, and Novartis; and travel grants from Pierre Fabre. MGM reports grant or research support from Ipsen, NuCana, and Servier; consulting fees from AstraZeneca and Incyte; and honoraria from Advanced Accelerator Applications and AstraZeneca. AA reports research funding from Amgen, Bayer, and Bristol Myers Squibb; and advisory fees from AstraZeneca, Amgen, Eisai, and MSD. JEC reports advisory fees from MSD; and fees as an invited speaker for AstraZeneca, Boehringer Ingelheim, Takeda, and Roche. VB reports consulting fees from Bayer, Bristol Myers Squibb Russia, Eisai, MSD, Novartis, Pfizer, Roche Russia, and Takeda; and travel expenses from Bayer, Bristol Myers Squibb Russia, MSD, and Roche Russia. BT reports research funding from Adaptimmune, AstraZeneca, Bristol Myers Squibb, and Exelixis. SS reports grant or research support from Delta-Fly Pharma and Incyte. DT reports personal fees for advisory board participation from Amgen, AstraZeneca, MSD, Pierre Fabre, Roche, Sanofi, and Servier. LE reports personal fees for advisory board participation from Amgen, Merk, MSD, and Servier. MP reports personal fees for advisory board participation from Roche and Servier; personal fees as an invited speaker from AstraZeneca, Ewopharma, and Takeda; and non-financial interests with AstraZeneca and Sanofi. DBZ reports advisory fees from Cornerstone Pharmaceuticals, Ipsen, Jazz Pharmaceuticals/Zymeworks, and QED Therapeutics; and research funding from AstraZeneca, Bayer, Bristol Meyers Squibb, Cornerstone Pharmaceuticals, Daiichi Sankyo, Eli Lily, Ipsen, Roche/Genentech, Legend Biotech, Merck, and Seagen. VGG holds stock in RPG Life Sciences and Zydus Lifesciences. FD reports grant or research support from Amgen, AstraZeneca, Bristol Myers Squibb, Exelixis, Genentech, Ipsen, Signatera, and Taiho Pharmaceutical; consulting fees from AstraZeneca, Eisai, Exelixis, Genentech, and Ipsen; and payment or honoraria from Astellas, Eisai, Exelixis, Ipsen, Servier, and Sirtex Medical. JOP reports advisory board fees from Adicet Bio, AstraZeneca, Bristol Myers Squibb (Celgene), MediRama, MedPacto, Merck Serono, and Servier; support for travel to meetings from Minneamrita Therapeutics; and grant or research support from ABL Bio, Bristol Myers Squibb (Celgene), Eutilex, MedPacto, and Servier. HK, CM, and MŻ are employees of AstraZeneca. JW and NR are employees of and hold stock in AstraZeneca. AV reports speaker fees from BeiGene, Bristol Myers Squibb, Eisai, Imaging Equipment, Incyte, Ipsen, Jiangsu Hengrui Pharmaceuticals, Eli Lilly, MSD, Novartis, Pierre Fabre, and Roche; and advisory fees from AstraZeneca, Bayer, Bristol Myers Squibb, Boston Scientific, Daiichi Sankyo, Eisai, Ipsen, Incyte, Lilly, MSD, Pierre Fabre, Roche, and Sirtex Medical. JWV reports advisory fees from Agios, AstraZeneca, Autem Therapeutics, Baxter, Hutchison MediPharma, Image Equipment, NuCana, QED Therapeutics, Sirtex Medical, Servier, and Zymeworks; speaker fees from Incyte, Ipsen, and Mylan; and research funding from AstraZeneca and Redx. All other authors declare no competing interests., (2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

What Is This Summary About?: This is a summary describing the results of a Phase III study called TOPAZ-1. The study looked at treatment with durvalumab (a type of immunotherapy) and chemotherapy to treat participants with advanced biliary tract cancer (BTC). Advanced BTC is usually diagnosed at late stages of disease, when it cannot be cured by surgery. This study included participants with advanced BTC who had not received previous treatment, or had their cancer come back at least 6 months after receiving treatment or surgery that aimed to cure their disease. Participants received treatment with durvalumab and chemotherapy or placebo and chemotherapy. The aim of this study was to find out if treatment with durvalumab and chemotherapy could increase the length of time that participants with advanced BTC lived, compared with placebo and chemotherapy., What Were the Results of the Study?: Participants who took durvalumab and chemotherapy had a 20% lower chance of experiencing death at any point in the study compared with participants who received placebo and chemotherapy. The side effects experienced by participants were similar across treatment groups, and less than 12% of participants in either treatment group had to stop treatment due to treatment-related side effects., What Do the Results of the Study Mean?: Overall, these results support durvalumab and chemotherapy as a new treatment option for people with advanced BTCs. Based on the results of this study, durvalumab is now approved for the treatment of adults with advanced BTCs in combination with chemotherapy by government organizations in Europe, the United States and several other countries.

Background: Although immune checkpoint inhibitors (ICIs) have become the frontline treatment option for patients with various advanced cancers due to improved survival, they can be associated with a spectrum of cutaneous immune-related adverse events (cirAEs). However, little is known regarding the occurrence and patterns of cirAE-related ICI therapy in patients of different races other than white populations. Therefore, we investigated the incidence and associated factors of cirAEs among cancer patients in northern Thailand., Methods: A referral-center-based ambispective cohort study was conducted from January 1, 2017, to March 31, 2021. Based on a linked database and merged patient-level data, adult patients with pathologically confirmed cancer who were diagnosed and received ICI therapy regardless of cancer type and followed up through August 31, 2021, were included. All cirAE-related ICI therapy was based on clinical evaluation and ascertainment by a board-certified dermatologist. The incidence of cirAE-related ICI therapy with confidence intervals (CIs) across cancer- and ICI therapy-specific groups was estimated. Factors associated with cirAEs were evaluated using multivariable modified Poisson regression to estimate risk ratios (RRs) and 95% CIs., Results: The study included 112 patients (67 men [59.8%]; mean age, 65.0 [range, 31.0-88.0] years), who were mainly diagnosed with lung cancer (56.3%), followed by liver cancer (19.6%). The overall incidence of cirAE-related ICI therapy was 32.1% (95% CI, 24.1-41.4); however, there was no substantial difference in sex, cancer type, or individual ICI therapy. The two identified prognostic risk factors of cirAE-related ICI therapy were age >75 years (adjusted RR, 2.13; 95% CI, 1.09-4.15; P =0.027) and pre-existing chronic kidney disease stages 3-4 (adjusted RR, 3.52; 95% CI, 2.33-5.31; P <0.001)., Conclusions: The incidence of cirAE-related ICI therapy among Thai cancer patients was comparable to that in white populations. Early identification, particularly in elderly patients and those with CKD, should be implemented in clinical practice to help optimize therapeutic decision-making and patient health outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luangnara, Kiratikanon, Ketpueak, Suksombooncharoen, Charoentum, Chewaskulyong, Tovanabutra, Chiewchanvit, Nochaiwong and Chuamanochan.)

BACKGROUND: Patients with advanced biliary tract cancer have a poor prognosis, and first-line standard of care (gemcitabine plus cisplatin) has remained unchanged for more than 10 years. The TOPAZ-1 trial evaluated durvalumab plus chemotherapy for patients with advanced biliary tract cancer. METHODS: In this double-blind, placebo-controlled, phase 3 study, we randomly assigned patients with previously untreated unresectable or metastatic biliary tract cancer or with recurrent disease 1:1 to receive durvalumab or placebo in combination with gemcitabine plus cisplatin for up to eight cycles, followed by durvalumab or placebo monotherapy until disease progression or unacceptable toxicity. The primary objective was to assess overall survival. Secondary end points included progression-free survival, objective response rate, and safety. RESULTS: Overall, 685 patients were randomly assigned to durvalumab (n=341) or placebo (n=344) with chemotherapy. As of data cutoff, 198 patients (58.1%) in the durvalumab group and 226 patients (65.7%) in the placebo group had died. The hazard ratio for overall survival was 0.80 (95% confidence interval [CI], 0.66 to 0.97; P=0.021). The estimated 24-month overall survival rate was 24.9% (95% CI, 17.9 to 32.5) for durvalumab and 10.4% (95% CI, 4.7 to 18.8) for placebo. The hazard ratio for progression-free survival was 0.75 (95% CI, 0.63 to 0.89; P=0.001). Objective response rates were 26.7% with durvalumab and 18.7% with placebo. The incidences of grade 3 or 4 adverse events were 75.7% and 77.8% with durvalumab and placebo, respectively. CONCLUSIONS: Durvalumab plus chemotherapy significantly improved overall survival versus placebo plus chemotherapy and showed improvements versus placebo plus chemotherapy in prespecified secondary end points including progression-free survival and objective response rate. The safety profiles of the two treatment groups were similar. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT03875235.)