A randomized phase III study of immune checkpoint inhibition with chemotherapy in treatment-naive metastatic anal cancer patients: A trial of the ECOG-ACRIN cancer research group (EA2176).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS3614-TPS3614
Author(s):  
Marc Thomas Roth ◽  
Paul J. Catalano ◽  
Kristen Keon Ciombor ◽  
Al Bowen Benson ◽  
Xin Yao ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cancer Progression ◽  
Phase Ii ◽  
Anal Cancer ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Phase Iii ◽  
Curative Intent ◽  
Platinum Based Chemotherapy ◽  
Treatment Naïve

TPS3614 Background: Anal cancer is growing in annual incidence globally and human papillomavirus (HPV) remains the predominant risk factor underlying its development. Due to its relative rarity, clinical trials in anal cancer have historically been difficult to conduct and treatment options for metastatic disease remain limited. Carboplatin/paclitaxel (CP) was compared to cisplatin/5-fluorouracil (historical standard of care) in a recent randomized phase II clinical trial (InterAACT; EA2133) in treatment-naïve metastatic anal cancer, finding that response rates were equivocal, but that overall survival (OS) was significantly longer in the CP arm (20 months vs 12.3 months, p = 0.014). Additionally, reduced grade 3/4 toxicities were seen in the CP arm. NCI9673, a single-arm phase II study, established safety and efficacy of nivolumab in previously-treated metastatic anal cancer. Progression-free survival (PFS) was 4.1 months (95% CI 3.0-7.9) and OS was 11.5 months (95% CI 7.1-not estimable). Multiple randomized trials in lung cancer have demonstrated efficacy of platinum-based chemotherapy combined with checkpoint inhibitors. Together these studies form the rationale behind combining CP and nivolumab in treatment-naïve metastatic anal cancer. Methods: EA2176 (NCT04444921) is the first NCTN phase III randomized clinical trial in treatment-naïve metastatic anal cancer. Stratification factors include HIV status and history of chemoradiation for curative intent. Patients will be randomized to carboplatin (AUC = 5, Day 1) plus paclitaxel (80mg/m2, Days 1, 8, 15) +/- nivolumab 240mg IV (Cycle 1 = Days 1, 15; Cycle ≥2 = Day 1, 480mg) q 28-days until disease progression or treatment intolerance. CP will be given for up to 6 cycles, while nivolumab will be continued as maintenance for up to 2 years. The primary endpoint is PFS. Secondary objectives include OS, response rate, and toxicity. Goal enrollment is 205 patients and the study continues accrual. This sample size will provide 80% power at a two-sided α of 0.05 to detect a 4.8-month improvement in PFS assuming 8 months in the control arm. Novel correlative studies include sequential quantitative tumor-derived cell-free HPV ctDNA levels (serotypes 16 and 18; Sysmex-Inostics SafeSEQ NGS assay). Correlative funding provided in part by the Farrah Fawcett Foundation and Sysmex Inostics, Inc. Clinical trial information: NCT04444921.

Cyto-KIK: A phase II trial of cytoreductive surgery in kidney cancer plus immunotherapy (nivolumab) and targeted kinase inhibition (cabozantinib).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4598-TPS4598
Author(s):  
Karie Runcie ◽  
Eric A. Singer ◽  
Moshe Chaim Ornstein ◽  
Christopher B. Anderson ◽  
Matthew Dallos ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Cytoreductive Nephrectomy ◽  
Open Label ◽  
Orthotopic Mouse Model

TPS4598 Background: Despite recent therapeutic advancements in metastatic renal cell carcinoma (mRCC), only 5-10% of patients will achieve a complete response (CR) to therapy. Cytoreductive nephrectomy removes a large portion of the tumor which may be a source of immunosuppression driven by tumor cell-intrinsic factors in the tumor microenvironment. A pre-clinical orthotopic mouse model of aggressive metastatic triple negative breast cancer showed that neoadjuvant anti-PD-1 checkpoint inhibition generated enhanced and sustained antitumor immune responses with improved survival compared to adjuvant therapy (Liu J et al. Cancer Discov. 2016:1382). Clinical validation of improved outcomes with neoadjuvant compared to adjuvant immune checkpoint inhibitors has been demonstrated in trials for patients with non-small cell lung cancer, advanced melanoma, and recurrent glioblastoma (Forde, P.M., et al. N Engl J Med. 2018:1976; Amaria, R.N., et al Nat Med. 2018:1649; Cloughesy T.F., et al. Nat Med 2019:477). Recent data from a phase III trial in subjects with untreated mRCC, demonstrated the superiority of combination cabozantinib and nivolumab over sunitinib and established a new standard of care for mRCC (Choueiri T.K., et al. Annals of Onc, 2020;31 (suppl; abstr 6960). We hypothesize that if tumor specific immune responses to immunotherapy are greatest prior to nephrectomy, then treatment with nivolumab (nivo) and cabozantinib (cabo) prior to cytoreductive nephrectomy will lead to maximal peripheral and intra-tumoral specific immune responses and higher rates of CR during the course of treatment. Methods: This is an open label phase II, multicenter clinical trial of combination nivo and cabo prior to cytoreductive nephrectomy in patients with mRCC (NCT04322955). 48 treatment- naïve subjects with radiological or histological diagnosis of mRCC will be enrolled with the primary endpoint of CR rate according to RECIST version 1.1. Subjects will receive cabo (40mg) daily and nivo (480mg) every 4 weeks for 12 weeks prior to nephrectomy and a 3+3 design will be used to evaluate the safety of the interval (21 or 14 days) between the discontinuation of cabo and nephrectomy. Post-operatively, subjects will resume treatment with cabo and nivo until evidence of disease progression. Secondary endpoints include median size reduction of the primary tumor, response rate, PFS, OS, and surgical outcomes using the Clavien-Dindo classification system. Tissue based assays will quantify treatment related changes in the renal tumor microenvironment through polychromatic immunofluorescence, single cell RNA sequencing of the biopsy and nephrectomy specimen, and multiplex assessment of circulating serum cytokines. Dynamic contrast-enhanced MRI will be performed in a subset of subjects to assess radiologic correlates of response. The study is currently open to enrollment. Clinical trial information: NCT04322955.

Phase II trial of cytoreductive surgery in kidney cancer plus immunotherapy (nivolumab) and targeted kinase inhibition (cabozantinib) (Cyto-KIK).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS371-TPS371
Author(s):  
Karie Runcie ◽  
Eric A. Singer ◽  
Moshe Chaim Ornstein ◽  
Christopher B. Anderson ◽  
Matthew Dallos ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Cytoreductive Nephrectomy ◽  
Open Label ◽  
Orthotopic Mouse Model

TPS371 Background: Despite recent therapeutic advancements in metastatic renal cell carcinoma (mRCC), only 5-10% of patients will achieve a complete response (CR) to therapy. Cytoreductive nephrectomy removes a large portion of the tumor which may be a source of immunosuppression driven by tumor cell-intrinsic factors in the tumor microenvironment. A pre-clinical orthotopic mouse model of aggressive metastatic triple negative breast cancer showed that neoadjuvant anti-PD-1 checkpoint inhibition generated enhanced and sustained antitumor immune responses with improved survival compared to adjuvant therapy (Liu J et al. Cancer Discov. 2016:1382). Clinical validation of improved outcomes with neoadjuvant compared to adjuvant immune checkpoint inhibitors has been demonstrated in trials for patients with non-small cell lung cancer, advanced melanoma, and recurrent glioblastoma (Forde, P.M., et al. N Engl J Med. 2018:1976; Amaria, R.N., et al Nat Med. 2018:1649; Cloughesy T.F., et al. Nat Med 2019:477). Recent data from a phase III trial in subjects with untreated mRCC, demonstrated the superiority of combination cabozantinib and nivolumab over sunitinib and established a new standard of care for mRCC (Choueiri T.K., et al. Annals of Onc, 2020;31 (suppl; abstr 6960). We hypothesize that if tumor specific immune responses to immunotherapy are greatest prior to nephrectomy, then treatment with nivolumab (nivo) and cabozantinib (cabo) prior to cytoreductive nephrectomy will lead to maximal peripheral and intra-tumoral specific immune responses and higher rates of CR during the course of treatment. Methods: This is an open label phase II, multicenter clinical trial of combination nivo and cabo prior to cytoreductive nephrectomy in patients with mRCC (NCT04322955). 48 treatment- naïve subjects with radiological or histological diagnosis of mRCC will be enrolled with the primary endpoint of CR rate according to RECIST version 1.1. Subjects will receive cabo (40mg) daily and nivo (480mg) every 4 weeks for 12 weeks prior to nephrectomy and a 3+3 design will be used to evaluate the safety of the interval (21 or 14 days) between the discontinuation of cabo and nephrectomy. Post-operatively, subjects will resume treatment with cabo and nivo until evidence of disease progression. Secondary endpoints include median size reduction of the primary tumor, response rate, PFS, OS, and surgical outcomes using the Clavien-Dindo classification system. Tissue based assays will quantify treatment related changes in the renal tumor microenvironment through polychromatic immunofluorescence, single cell RNA sequencing of the biopsy and nephrectomy specimen, and multiplex assessment of circulating serum cytokines. Dynamic contrast-enhanced MRI will be performed in a subset of subjects to assess radiologic correlates of response. The study is currently open to enrollment. Clinical trial information: AAAS6927 .

A randomized phase II study of durvalumab and tremelimumab compared to doxorubicin in patients with advanced or metastatic soft tissue sarcoma (MEDISARC, AIO-STS 0415).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS11075-TPS11075
Author(s):  
Viktor Grünwald ◽  
Sebastian Bauer ◽  
Barbara Hermes ◽  
Philipp Ivanyi ◽  
Lars H Lindner ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Soft Tissue ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Soft Tissue Sarcomas ◽  
Predictive Biomarkers ◽  
Ecog Performance Status ◽  
Curative Intent

TPS11075 Background: Soft tissue sarcomas (STS) are rare tumors and exhibit substantial histological diversity. Efficacious targeted 1st line treatment for advanced or metastatic STS is not available, and the standard therapy has been anthracycline-based for decades. This strategy shows poor efficacy, as demonstrated by a median Overall Survival (OS) of 12-20 months. Several STS subtypes, however, have been shown to express PD-L1, and immune checkpoint inhibitors (ICI) have demonstrated principle anti-tumor activity in pretreated STS. Our ongoing clinical trial tests the activity and safety of ICI combination therapy in the first-line setting. We hypothesize that the dual checkpoint blockade with Durvalumab (PD-L1) and Tremelimumab (CTLA-4) improves overall survival in STS when compared to the standard of care doxorubicin. Methods: MEDISARC is a multi-center phase II trial that is enrolling adult treatment-naïve patients with histologically confirmed STS of intermediate or high grade (FNCLCC grade 2 or 3) not amenable to surgery with curative intent and ECOG performance status 0-2. Chemosensitive histologic STS are eligible. 100 patients will be randomized 1:1, stratified by ECOG status (0 vs. 1/2). Patients in the experimental arm are treated with fixed doses of durvalumab (1.5 g Q4W) and tremelimumab (75 mg Q4W for 3 cycles, then Q12W) until Progressive Disease (PD) or for a maximum of 12 months. Doxorubicin treatment in the standard arm is at 75 mg/m2 Q3W and limited to 6 cycles. OS is the primary endpoint. Secondary endpoints include 2-year OS rate, PFS, ORR according to conventional and modified RECIST 1.1, safety and tolerability and health-related quality of life (EORTC QLQ-C30). OS analysis may be performed when the required number of events (E=70) has been observed. All randomized and treated subjects will be included in the efficacy and safety analysis. The accompanying translational research aims to identify prognostic and predictive biomarkers in blood and tumor tissue. Enrollment of patients started in April 2018 and is ongoing. As of February 2019, 32 patients have been enrolled. The study is sponsored by AIO-Studien-gGmbH, Berlin, Germany. Clinical trial information: 2016-004750-15.

Anlotinib plus sintilimab in patients with recurrent advanced cervical cancer: A prospective, multicenter, single-arm, phase II clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5524-5524
Author(s):  
Qin Xu ◽  
Chuanben Chen ◽  
Yang Sun ◽  
Zhangzhou Huang ◽  
Yibin Lin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cervical Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Checkpoint Inhibitors ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Advanced Cervical Cancer ◽  
Median Response ◽  
Platinum Based Chemotherapy

5524 Background: It is difficult for patients with recurrent advanced cervical cancer to obtain clinical benefits after the failure of standard chemotherapy. However, antiangiogenic therapy combined with immune checkpoint inhibitors have become a promising strategy for advanced cervical cancer. Anlotinib is a novel multi-target tyrosine kinase inhibitor, inhibiting tumour angiogenesis and proliferative signalling. Sintilimab is a fully humanized, high-affinity monoclonal antibody against programmed cell death-1 (PD-1). This phase II, single-arm study (ChiCTR1900023015) aims to evaluate the efficacy and safety of anlotinib plus sintilimab in patients with recurrent advanced cervical cancer. Methods: Patients who have received at least once platinum-based chemotherapy, histopathologically confirmed recurrent advanced cervical cancer (including squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma), more than 1% PD-L1 expression, ECOG 0-1 were considered eligible for enrollment. Anlotinib was taken orally (10mg mg qd, d1-14, 21 days per cycle), and sintilimab was administered intravenously (200mg once every 3 weeks). The treatment was continued until disease progression, death or intolerant toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. Results: Between September 2019 and February 2021, 42 patients with a median age of 52 years (range:47-58), FIGO histopathological stage I (11.9%), II (31.0%), III (33.3%), IV (9.5%) and undiagnosed (14.3%) were enrolled. 39 of these patients were evaluable. In the efficacy-evaluable population (n = 39), the therapeutic evaluation showed that 2 and 20 patients achieved complete response and partial response respectively, yielding the ORR of 56.4% (22/39, 95% CI:40.2 to 71.5). The DCR was 94.9% (37/39, 95% CI:80.7 to 98.8). The median response time was 1.6 months. The median PFS was not reached. The most common adverse events (AEs) were grade 1 or 2, which included hypothyroidism (33.3%), hypertension (23.8%), AST (21.4%), diarrhea (19.0%), ALT (16.7%), hand-foot syndrome(14.3%), hypertriglyceridemia (14.3%) and anemia (11.9%). The grade 3 AEs were hypertension (4.8%), hyponatremia (4.8%), immune pneumonia (2.4%) and immune myocarditis (2.4%). No higher AEs and treatment-related death were observed. Conclusions: Anlotinib plus sintilimab showed a promising efficacy with a favorable toxicity profile for patients with recurrent advanced cervical cancer. We will report more data in the future. Clinical trial information: ChiCTR1900023015.

scholarly journals Predictive Biomarkers for Checkpoint Inhibitor-Based Immunotherapy in Hepatocellular Carcinoma: Where Do We Stand?

2021 ◽  
Vol 11 ◽  
Author(s):  
Alessandro Rizzo ◽  
Angela Dalia Ricci ◽  
Alessandro Di Federico ◽  
Giorgio Frega ◽  
Andrea Palloni ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Anticancer Agents ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Phase Iii ◽  
Cochrane Library ◽  
Advanced Hcc ◽  
Treatment Naïve

Hepatocellular carcinoma (HCC) remains the sixth most commonly diagnosed malignancy worldwide, still representing an important cause of cancer-related death. Over the next few years, novel systemic treatment options have emerged. Among these, immune checkpoint inhibitors (ICIs) have been widely evaluated and are under assessment, as monotherapy or in combination with other anticancer agents in treatment-naïve and previously treated patients. In particular, the approval of the PD-L1 inhibitor atezolizumab plus the antiangiogenic agent bevacizumab as front-line treatment for advanced HCC has led to the adoption of this combination in this setting, and the IMbrave 150 phase III trial has established a novel standard of care. However, several questions remain unanswered, including the identification of reliable predictors of response to ICIs in HCC patients. In the current paper, we will provide an updated overview of potentially useful predictive biomarkers of response to immunotherapy in advanced HCC. A literature search was conducted in September 2021 of Pubmed/Medline, Cochrane library and Scopus databases.

scholarly journals Unresectable pleural mesothelioma—hope or still an unmet medical need?

2021 ◽  
Author(s):  
Gudrun Absenger ◽  
Angelika Terbuch
Keyword(s):  
Overall Survival ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
Phase Iii ◽  
Pleural Mesothelioma ◽  
The European Union ◽  
Rare Tumour ◽  
Dismal Prognosis ◽  
Platinum Based Chemotherapy

SummaryMalignant pleural mesothelioma (MPM) is a rare tumour that originates from the inner linings of the pleural cavity. The majority of cases are associated with exposure to asbestos for what was banned in the European Union in 1991. Due to the long latency between exposure and onset (20–40 years) the peak of MPM in Western Europe will be reached within the next years. Often diagnosed at an unresectable stage, treatment options remain palliative in the majority of cases. The highly aggressive nature of MPM leads to a dismal prognosis with a median overall survival of approximately one year.Platinum-based chemotherapy in combination with pemetrexed has been the mainstay of first line treatment in unresectable MPM for many years. Only recently, check point inhibitors have found their way into MPM treatment. The results of the phase III CheckMate 743 trial last year have finally led to a paradigm shift in the treatment of unresectable MPM. This trial showed a significant overall survival benefit for the combination of nivolumab and ipilimumab over standard chemotherapy, especially in nonepithelioid histology. Apart from histology, predictive biomarkers have not been identified for the treatment of MPM so far. Several trials investigating combination therapies with checkpoint inhibitors are currently ongoing and give hope to further improve prognosis for our patients.

624 A PHASE III STUDY ON NEOADJUVANT TORIPALIMAB PLUS CHEMOTHERAPY VERSUS NEOADJUVANT CHEMOTHERAPY FOR LOCALLY RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Yan Zheng ◽  
Jiangong Zhang ◽  
Wenqun Xing
Keyword(s):  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
R0 Resection ◽  
Phase Iii Trial ◽  
Free Survival

Abstract   In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in our Hospital. Methods A two-arm phase III trial was launched in April 2020 in our Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future. Results Until Dec. 2021, one hundred and twenty ESCC patients recruited in the trial. The trial is ongoing. Conclusion This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment.

Anlotinib combined with pemetrexed and carboplatin as first-line treatment in advanced nonsquamous non-small cell lung cancer (NSCLC): ALTER L012.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21040-e21040
Author(s):  
Qiming Wang ◽  
Xiuli Yang ◽  
Tianjiang Ma ◽  
Qiumin Yang ◽  
Chenghui Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Treatment Naïve ◽  
Nsclc Patients ◽  
First Line Treatment

e21040 Background: The anti-angiogenic drug bevacizumab combined with chemotherapy has achieved positive results in previous studies. In particular, the median progression-free survival (PFS) for EGFR-negative patients was increased to 8.3 months in the BEYOND study. Unlike bevacizumab, anlotinib is a novel multitarget tyrosine kinase inhibitor and can be conveniently orally administered. In the phase III trial ALTER 0303, anlotinib significantly improved overall survival (OS) and PFS in advanced NSCLC patients. This exploratory study aims to establish the efficacy and safety of anlotinib in combination with pemetrexed and carboplatin as first-line treatment in advanced non-squamous NSCLC. Methods: This is a multi-center, single-arm clinical trial. Adults with treatment-naive, histologically confirmed stage IIIB-IV non-squamous NSCLC, ECOG 0-1, and without known sensitizing EGFR/ALK alterations are included. Patients received anlotinib (12 mg p.o., QD, d1 to 14, 21 days per cycle) combined with pemetrexed (500 mg/m2, iv, d15-21, Q3W) + carboplatin (AUC = 5, iv, d15-21, Q3W) for 4 cycles followed by anlotinib and pemetrexed maintenance until disease progression (PD). The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: Between Mar 2019 and Dec 2020, 40 patients were enrolled in six centers and 31 of them have received at least one tumor assessment. Median age was 62 (33, 75); 66.7% male, 11.1% brain metastasis. At data cutoff (Dec 31, 2020), patients were followed up for a median of 8.26 months. Median PFS was 10.5 months (95% CI: NE, NE); ORR was 67.7% (0 CR, 21 PR), DCR was 96.8% (0 CR, 21 PR, 9 SD) and median OS was NE. The most common Grade ≥ 3 AEs were hypertension 22.2%, neutropenia 19.44%, myelosuppression 11.1%, thrombocytopenia 8.33%, leukopenia 5.56%, hand-foot syndrome 5.56% and there were no Grade 5 toxicities. Conclusions: This study finds that anlotinib plus pemetrexed and carboplatin can significantly improve PFS and ORR compared to standard chemotherapy for treatment-naive non-squamous NSCLC patients. The combination was well tolerated, and the AEs were manageable. The follow-up time is not sufficient, and the OS outcomes need further evaluation. Clinical trial information: NCT03790228.

Tildrakizumab: A Review of Phase II and III Clinical Trials

2018 ◽  
Vol 53 (4) ◽  
pp. 413-418 ◽  
Author(s):  
Sree S. Kolli ◽  
Sarah D. Gabros ◽  
Adrian Pona ◽  
Abigail Cline ◽  
Steven R. Feldman
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Biological Therapy ◽  
Common Adverse Effect ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Severe Psoriasis ◽  
Phase Iii ◽  
Physician Global Assessment ◽  
Phase Ii And Iii

Objective: Tildrakizumab, an inhibitor of the p19 subunit of interleukin (IL)-23, was recently Food and Drug Administration (FDA) approved for patients with moderate to severe psoriasis. This article will review the phase II and III clinical trial data of tildrakizumab. Data Sources: A PubMed search from January 2000 to September 2018 was done with the search terms tildrakizumab, guselkumab, risankizumab, p19, interleukin-23, and psoriasis. Study Selection and Data Extraction: Articles discussing phase II and III clinical trial data for tildrakizumab were selected. Data Synthesis: In phase II and phase III trials, tildrakizumab was safe and efficacious compared with placebo and etanercept. More patients achieved Psoriasis Area and Severity Index 75 receiving tildrakizumab (200 mg, 62%-74%; 100 mg, 61%-66%; 25 mg, 64%; 5 mg, 33%) compared with placebo (4%-6%, P < 0.0001) and etanercept (48%, P = 0.01). More patients achieved Physician Global Assessment (PGA) response of “clear” or “minimal” receiving tildrakizumab (200 mg, 59%; 100 mg, 55%-58%) than the placebo group (4%-7%, P < 0.0001). 59% of patients who received tildrakizumab 200 mg achieved a PGA response of “clear” or “minimal” compared with etanercept (48%, P = 0.0031). The most common adverse effect was infection. Relevance to Patient Care and Clinical Practice: Tildrakizumab is a new, FDA-approved, physician-administered biological therapy for patients with moderate to severe psoriasis. It appears to be efficacious and safe so far. Conclusion: Tildrakizumab is efficacious and safe for the treatment of patients with moderate to severe psoriasis. IL-23/p19 inhibitors are a promising class of biological therapy.

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