Crizotinib Versus Chemotherapy on ALK-positive NSCLC: A Systematic Review of Efficacy and Safety

2018 ◽  
Vol 19 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Mingxia Wang ◽  
Guanqi Wang ◽  
Haiyan Ma ◽  
Baoen Shan
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Objective Response Rate ◽  
Retrospective Studies ◽  
Response Rate ◽  
Objective Response ◽  
Treated Group ◽  
Efficacy And Safety ◽  
Alk Positive

Introduction: Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)- positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011.We conducted a systematic review of clinical trials and retrospective studies to compare the efficacy and safety of crizotinib with chemotherapy. </P><P> Methods: We searched electronic databases from inception to Dec. 2016. Clinical trials and retrospective studies regarding crizotinib and crizotinib versus chemotherapy in treatment of NSCLC were eligible. The primary outcomes were the objective response rate (ORR) and disease control rate (DCR). Results: Nine studies (five clinical trials and four retrospective studies) including 729 patients met the inclusion criteria. Crizotinib treatment revealed 1-year OS of 77.1% and PFS of 9.17 months. And crizotinib had a better performance than chemotherapy in ORR (OR: 4.97, 95%CI: 3.16 to 7.83, P<0.00001, I2=35%). DCR revealed superiority with crizotinib than chemotherapy (OR: 3.42, 95% CI: 2.33 to 5.01, P<0.00001, I2=0%). PR (partial response) were significant superior to that of chemotherapy through direct systematic review. No statistically significant difference in CR (complete response) was found between crizotinib-treated group and chemotherapy-treated group. Regarding SD (stable disease), chemotherapy-treated group had a better performance than crizotinib-treated group. Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, nausea, and hematologic toxicity. This systematic review revealed improved objective response rate and increased disease control rate in crizotinib group comparing with chemotherapy group. Crizotinib treatment would be a favorable treatment option for patients with ALK-positive NSCLC. ALK inhibitors may have future potential applications in other cancers driven by ALK or c-MET gene mutations.

A randomized phase III study comparing carboplatin with nab-paclitaxel versus docetaxel for elderly patients with squamous-cell lung cancer: Capital study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9031-9031
Author(s):  
Yoichiro Hamamoto ◽  
Yoshihito Kogure ◽  
Akiko Kada ◽  
Hiroya Hashimoto ◽  
Shinji Atagi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Adverse Events ◽  
Elderly Patients ◽  
Cell Lung Cancer ◽  
Primary Endpoint ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Phase Iii

9031 Background: Cytotoxic monotherapy is one of the standard treatments for elderly patients with advanced non-small cell lung cancer (NSCLC). Carboplatin plus nab-paclitaxel demonstrated significantly higher objective response rate (ORR) than carboplatin plus paclitaxel in patients with squamous histology and could improve overall survival (OS) in patients aged ≥70 years. Here, we compared carboplatin plus nab-paclitaxel with docetaxel in elderly patients with squamous NSCLC. Methods: The CAPITAL study is a multicenter, open-label, phase 3, randomized trial at 92 institutions in Japan. Eligible patients had advanced squamous NSCLC with no prior systemic chemotherapy, aged ≥70 years, and had an ECOG performance status of 0 or 1. Patients were randomized 1:1 to docetaxel 60 mg/m2 (D arm) or carboplatin AUC 6 mg/mL/min plus nab-paclitaxel 100 mg/m2 weekly (nab-PC arm) for each 21-day cycle. The primary endpoint was OS. This trial is registered with the UMIN Clinical Trials Registry (UMIN000019843) and the Japan Registry of Clinical Trials (jRCTs041180110). Results: Between December 2015 and August 2020, 196 patients were randomly assigned to the two treatment arms (D arm, n=98; nab-PC arm, n=98). The median follow-up and age were 11.5 months and 76 years (range: 70–88 years), respectively, and 87% of the patients were male. After the planned interim analysis, the independent data monitoring committee confirmed that the study met the primary endpoint of improved OS in August 2020, and this report represents the final analysis. The nab-PC arm showed significant superiority in OS versus the D arm (hazard ratio [HR], 0.52; 90% CI, 0.38-0.70; median, 16.9 vs. 10.9 months; p<0.001). There were also significant improvements in progression-free survival (median, 5.8 vs. 4.0 months; HR, 0.42; 95% CI, 0.30-0.58; p<0.001) and objective response rate (66.3 vs. 28.0 %; p<0.001) in the nab-PC arm versus the D arm. The most common grade 3 or 4 adverse events were leukopenia (46.3 %), neutropenia (63.2 %), and anemia (38.9 %) in the nab-PC arm, and leukopenia (56.7 %), neutropenia (77.3 %), and febrile neutropenia (17.5 %) in the D arm. As notable adverse events, grade ≥2 sensory peripheral neuropathy was observed in 15 (15.8%) and 1 (1.0%) patient in the nab-PC and D arms, respectively. Moreover, serious treatment-related adverse events and treatment-related deaths occurred in 14 (14.7%) and 12 (12.4%) patients and in two and one patient in the nab-PC and D arms, respectively. Conclusions: The nab-PC arm had a significantly improved OS than the D arm among elderly patients with squamous NSCLC. Carboplatin plus nab-paclitaxel became a new standard treatment for these patients. Clinical trial information: UMIN000019843.

Safety and efficacy of nivolumab plus recombinant human endostatin in previously treated advanced non-small cell lung cancer: A prospective and multicenter phase 2 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21079-e21079
Author(s):  
Weize Lv ◽  
Beilong Zhong ◽  
Wenhua Zhao ◽  
Zhong Lin ◽  
Xiaofeng Pei ◽  
...  
Keyword(s):  
Adverse Events ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
First Line ◽  
Recombinant Human Endostatin ◽  
Phase 2 Trial

e21079 Background: Although the administration of immune checkpoint inhibitors (ICIs) and antiangiogenic agents in advanced non–small-cell lung cancer (NSCLC) has been well established, evidence supporting the combination of immune checkpoint inhibitors plus antiangiogenic drugs in previous treatment patients with advanced NSCLC is insufficient. We aimed to investigate the efficacy and safety of nivolumab combined with recombinant human endostatin (rh-Endostatin) as second-line or later treatment for advanced NSCLC. Methods: In this prospective and multicentre phase 2 trial we enrolled patients with advanced NSCLC who had not responded to standardized first-line treatment regimen from two cancer centres in China. Eligible patients were those aged 18-75 years without ICIs in first-line treatment who received nivolumab (3mg/kg, intravenous drip, day 1) every 2 weeks and rh-Endostatin (30 mg, 24-hour continous intravenous infusion，day 1–7) every 4 weeks till disease progression or discontinuation. The primary end points were objective response rate and safety. This study is registered with Chinese Clinical Trial Registry, number ChiCTR1900023664. Results: A total of 35 patients (median age, 60 years; range, 37-72 years) received nivolumab and rh-Endostatin. Median previous treated line of eligible patients was 2 lines (range, 1-7 lines). Patients received a median of 2 cycles of therapy (range, 1-14 cycles). Eleven of 33 evaluable patients achieved confirmed partial response with an objective response rate of 33.3% (11/33, 95% confidence interval [CI]: 17.2% – 49.4%) and disease control rate of 60.6% (20/33,95%CI:43.9%–77.3%). Median follow-up was 8.2 months (range: 0.9 –17.1). Median progression-free survival was 7.1 months (95% CI: 1.2m–13.0m), median overall survival was not reached and the 6-month overall survival rate was 54.5% (95% CI:37.6%–71.4%). The predominant grade 1-2 adverse events were thyroiditis, arrhythmia, hypertension. The grade 3 treatment-related adverse events were pneumonitis (3/35, 8.6%), hypertension (1/35, 2.9%) and atrial fibrillation (1/35, 2.9%), respectively. No grade 4 or 5 treatment-related adverse events were observed. Conclusions: To the best of our knowledge, this is the first prospective study that assessed nivolumab combined with rh-Endostatin as second-line or later treatment in pretreated patients with advanced NSCLC. In view of its encouraging efficacy and safety profile, nivolumab plus rh-Endostatin represents a promising treatment regimen in this patient population. Clinical trial information: ChiCTR1900023664.

scholarly journals Impact of Baseline ALBI Grade on the Outcomes of Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Multicenter Study

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 952 ◽  
Author(s):  
Kazuomi Ueshima ◽  
Naoshi Nishida ◽  
Satoru Hagiwara ◽  
Tomoko Aoki ◽  
Tomohiro Minami ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Adverse Events ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Treatment Discontinuation ◽  
The Impact ◽  
Group 1

Background: This study investigated the impact of baseline liver function according to the Child–Pugh score and ALBI (albumin-bilirubin) grade on the outcomes of patients with unresectable hepatocellular carcinoma treated with lenvatinib. Methods: A total of 82 lenvatinib treated patients were included. The correlations of baseline liver function according to the Child–Pugh score and ALBI grade with treatment outcomes, including objective response rate per mRECIST (modified Response Evaluation Criteria in the Solid Tumor), time to treatment failure, treatment duration, and likelihood of treatment discontinuation due to adverse events, were assessed in patients with hepatocellular carcinoma treated with lenvatinib. Patients were divided into four groups: (1) Child–Pugh score 5 and ALBI grade 1 (group 1), (2) Child–Pugh score 5 and ALBI grade 2 (group 2), (3) Child–Pugh score 6 (group 3), and (4) Child–Pugh score ≥7 (group 4). Univariate and multivariate analyses were performed to identify the factors contributing to the objective response rate and likelihood of discontinuation due to adverse events. Results: Among the 82 patients analyzed, group 1 had the highest objective response rate (57.1%) and the lowest likelihood of treatment discontinuation because of adverse events (11.1%) among the four groups (p < 0.05 and p < 0.05). Multivariate analysis identified ALBI grade 1 and baseline AFP level <200 ng/mL as the significant predictors of a high objective response rate (p < 0.05 and p < 0.01), and confirmed that patients with ALBI grade 1 had the lowest probability of treatment discontinuation due to adverse events (p < 0.01). Conclusions: Patients with Child–Pugh score of 5 and ALBI grade 1 predicted a higher response rate and lower treatment discontinuation due to adverse events by lenvatinib treatment.

scholarly journals Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Yufeng Yin ◽  
Mingjun Wang ◽  
Mengru Liu ◽  
Erye Zhou ◽  
Tian Ren ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ankylosing Spondylitis ◽  
Adverse Events ◽  
Response Rate ◽  
Phase Iii ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
End Point ◽  
Increased Risk ◽  
Severe Infections

Abstract Objectives: To systematically assess the efficacy and safety of IL-17 inhibitors in patients with active ankylosing spondylitis. Methods: A systematic review of the literature was performed for randomized controlled trials (RCTs) concerning IL-17 inhibitors in patients with ankylosing spondylitis. Meta-analyses were used to determine the efficacy and safety of the IL-17 inhibitors in the treatment of these patients. The primary end point was predefined as the proportion of patients with at least 20% improvement in the Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16, and the secondary end point was defined as ASAS40 at week 16. Results: Six phase III randomized, double-blind, placebo-controlled trials including 1733 patients (1153 patients received IL-17 inhibitors, including secukinumab or ixekizumab, whereas 580 patients received a placebo as comparators) were included. At week 16, the IL-17 inhibitor regimen produced a significant increase in the ASAS20 response rate (RR=1.63, 95% CI 1.45 to 1.84, p=0.00) and the secondary endpoint ASAS40 response rate (RR=2.12, 95% CI 1.75 to 2.56, p=0.00) versus those for the placebo. With respect to the safety profile, more treatment-emergent adverse events (RR=1.11, 95% CI 1.01 to 1.22, p=0.03) and non-severe infections (RR=1.82, 95% CI 1.40 to 2.37, p<0.001) were described after treatment with IL-17 inhibitors than after treatment with placebo, while no increased risk of other adverse events was indicated after IL-17 inhibitor therapy, including death, discontinuation due to adverse events, or serious adverse events. Conclusions: IL-17 inhibitors produced favourable response rates but an increased risk of non-severe infections in the treatment of active ankylosing spondylitis.

scholarly journals Efficacy and safety of lenvatinib in combination with everolimus in metastatic renal cell carcinoma resistant to antiangiogenic targeted therapy: Russian multicenter observational study ROSLERCM

2019 ◽  
Vol 15 (3) ◽  
pp. 56-69 ◽  
Author(s):  
M. I. Volkova ◽  
A. M. Abdelgafur ◽  
M. T. Aivazov ◽  
Z. V. Amoev ◽  
K. G. Babina ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Adverse Events ◽  
Observational Study ◽  
Response Rate ◽  
Objective Response ◽  
Tumor Control ◽  
Efficacy And Safety ◽  
Multicenter Observational Study ◽  
Grade Iii

Objective: an assessment of efficacy and safety of lenvatinib in combination with everolimus in unselected patients with metastatic renal cell carcinoma (mRCC) progressed during or following ≥1 line of antiangiogenic targeted therapy.Material. Russian multicenter observational study ROSLERCM included 73 consecutive patients with morphologically verified mRCC progressed during or following ≥1 line of antiangiogenic targeted therapy, treated with lenvatinib (18 mg/d) and everolimus (5 mg/d) in 20 Russian centers. Median age of the patients was 59 (23–73) years, a male-to-female ratio – 3:1. Most common histological type of kidney cancer was clear-cell RCC (71 (95.8 %)). More than 2 lines of previous therapy were administered in 45 (61.6 %) cases. Most patients were diagnosed with multiple metastases (71 (97.3 %)) in >1 site (61 (83.6 %)). Nephrectomy was performed in 87.7 % (64/73) of cases. At the combined therapy start ECOG PS 2–4 was registered in 16 (20.5 %), poor prognosis according to IMDC score – in 33 (45.2 %) patients. Median follow-up was 9.7 (1–26) months.Results. Median progression-free survival achieved 16.9 (95 % confidence intervals (CI) 12.1–20.6), overall survival – 20.8 (95 % CI 15.7–25.9) months. Objective response rate was 11 % (8/73); tumor control was reached in 93.2 % (68/73) of cases. Median objective response duration was 10.5 (4.3–16.8) months, tumor control duration – 10.0 (2.5–17.5) months. Any adverse events developed in 83.6 % (61/73), adverse events grade III–V – in 23.3 % (17/73) of cases. Most frequent AE grade III–IV were diarrhea (10 (13.6 %)) and arterial hypertension (6 (8.2 %)). Unacceptable toxicity demanded treatment cancellation in 4.2 % (3/73), therapy interruption – in 30.1 % (22/73) and dose reduction – in 32.9 % (24/73) of patients.Conclusion. Unselected mRCC patients administered with combined targeted therapy in the real world practice were registered with similar survival, lower objective response rate, and better tolerability comparing with population assigned for lenvatinib plus everolimus in the randomized phase II trial.

scholarly journals Phase 2 study of axicabtagene ciloleucel in Japanese patients with relapsed or refractory large B-cell lymphoma

2021 ◽  
Author(s):  
Koji Kato ◽  
Shinichi Makita ◽  
Hideki Goto ◽  
Junya Kanda ◽  
Nobuharu Fujii ◽  
...  
Keyword(s):  
B Cell ◽  
Objective Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Objective Response ◽  
B Cell Lymphoma ◽  
Japanese Patients ◽  
Efficacy And Safety ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background Axicabtagene ciloleucel (axi-cel) is an autologous chimeric antigen receptor T-cell based anti-CD19 therapy. The ZUMA-1 study, multicenter, single-arm, registrational Phase 1/2 study of axi-cel demonstrated high objective response rate in patients with relapsed/refractory large B-cell lymphoma. Here, we present the results of the bridging study to evaluate the efficacy and safety of axi-cel in Japanese patients (JapicCTI-183914). Methods This study was the phase 2, multicenter, open-label, single-arm trial. Following leukapheresis, axi-cel manufacturing and lymphodepleting chemotherapy, patients received a single infusion of axi-cel (2.0 × 106 cells/kg). Bridging therapy between leukapheresis and conditioning chemotherapy was not allowed. The primary endpoint was objective response rate. Results Among 17 enrolled patients, 16 received axi-cel infusion. In the 15 efficacy evaluable patients, objective response rate was 86.7% (95% confidence interval: 59.5–98.3%); complete response/partial response were observed in 4 (26.7%)/9 (60.0%) patients, respectively. No dose-limiting toxicities were observed. Grade ≥ 3 treatment-emergent adverse events occurred in 16 (100%) patients—most commonly neutropenia (81.3%), lymphopenia (81.3%) and thrombocytopenia (62.5%). Cytokine release syndrome occurred in 13 (81.3%) patients (12 cases of grade 1 or 2 and 1 case of grade 4). No neurologic events occurred. Two patients died due to disease progression, but no treatment-related death was observed by the data-cutoff date (October 23, 2019). Conclusion The efficacy and safety of axi-cel was confirmed in Japanese patients with relapsed/refractory large B-cell lymphoma who have otherwise limited treatment options. Trial registration JapicCTI-183914.

scholarly journals Pembrolizumab Monotherapy for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Arm Phase II Trial (KEYNOTE-629)

2020 ◽  
Vol 38 (25) ◽  
pp. 2916-2925 ◽  
Author(s):  
Jean-Jacques Grob ◽  
Rene Gonzalez ◽  
Nicole Basset-Seguin ◽  
Olga Vornicova ◽  
Jacob Schachter ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Free Survival ◽  
Duration Of Response

PURPOSE Treatment options are limited for patients with recurrent and/or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC); mortality rates exceed 70% in patients with distant metastases. Here, we present the first interim analysis of the R/M cSCC cohort from the 2-cohort—locally advanced and R/M—phase II KEYNOTE-629 study. PATIENTS AND METHODS Patients with R/M cSCC not amenable to surgery or radiation received pembrolizumab 200 mg every 3 weeks. The primary end point was objective response rate per RECIST v1.1. Secondary end points were duration of response, disease control rate, progression-free survival, overall survival, and safety. RESULTS At data cutoff (April 8, 2019), median follow-up of 105 enrolled patients in the R/M cohort was 11.4 months (range, 0.4 to 16.3 months). Objective response rate was 34.3% (95% CI, 25.3% to 44.2%; 4 complete responses, 32 partial responses), and disease control rate was 52.4% (95% CI, 42.4% to 62.2%). Median duration of response was not reached (range, 2.7 to 13.1+ months; ‘+’ refers to ongoing response at data cutoff). Median progression-free survival was 6.9 months (95% CI, 3.1 months to 8.5 months). Median overall survival was not reached (95% CI, 10.7 months to not reached). Treatment-related adverse events occurred in 66.7% of patients (n = 70), the most common of which were pruritus (n = 15; 14.3%), asthenia (n = 14; 13.3%), and fatigue (n = 13; 12.4%). Grade 3 to 5 treatment-related adverse events occurred in 5.7% (n = 6) of patients. One patient died of treatment-related cranial nerve neuropathy. CONCLUSION Pembrolizumab demonstrated effective antitumor activity; clinically meaningful, durable responses; and acceptable safety in primarily elderly patients with R/M cSCC, supporting its use in clinical practice. Pembrolizumab adverse events in this study were consistent with its established safety profile.

Efficacy and safety of localized concurrent chemoradiation therapy and sorafenib sequential therapy in advanced hepatocellular carcinoma: A prospective phase II trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15678-e15678
Author(s):  
Beom Kyung Kim ◽  
Do Young Kim ◽  
Hye Jin Choi ◽  
Seung-Hoon Beom ◽  
Hye Won Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Objective Response Rate ◽  
Median Overall Survival ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Sorafenib Treatment

e15678 Background: Patients with advanced hepatocellular carcinoma (HCC) have a particularly poor prognosis of the median overall survival of less than 12 months. Even though sorafenib has been approved for treating advanced stage HCC, the unsatisfactory objective response rate still remain unresolved. In the current study, we aimed to evaluate the efficacy and safety of localized concurrent chemoradiotherapy (CCRT) followed by sequential sorafenib treatment for advanced hepatocellular carcinoma. Methods: This study is an ongoing, phase II trial. Patients with advanced HCC not amenable for curative treatments were eligible. In the course of radiotherapy for 5 weeks, hepatic arterial infusion of 5-fluorouracil (500mg/day) via implanted port was applied during the first 5 days and the last 5 days of radiotherapy. Four weeks after localized CCRT, sorafenib (400mg bid) was maintained. The primary endpoint was overall survival. Results: A total of 47 patients were enrolled. After the completion of localized CCRT, the objective response rate was 31.9%. During the overall treatment course, the objective response rate was 46.8% respectively. Overall, 7 patients (14.9%) underwent curative resection or transplantation after down-staging. The median overall survival was 18.4 months and the progression-free survival was 6.8 months. Adverse events were predictable and manageable with conservative care. Conclusions: Localized CCRT followed by sequential sorafenib treatment in patients with advanced HCC showed significant activity and good tolerability. Furthermore, such a treatment modality, when compared to the use of sorafenib alone, might provide the additional therapeutic benefit through initial tumor reduction, allowing curative treatment after down-staging in 14.9% of patients, Further randomized trial should be required to make the more robust evidence. Clinical trial information: NCT02425605.

Envafolimab (KN035) in advanced tumors with mismatch-repair deficiency.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3021-3021
Author(s):  
Lin Shen ◽  
Jian Li ◽  
Yanhong Deng ◽  
Weijie Zhang ◽  
Aiping Zhou ◽  
...  
Keyword(s):  
Adverse Events ◽  
Mismatch Repair ◽  
Objective Response Rate ◽  
Interim Analysis ◽  
Response Rate ◽  
Objective Response ◽  
Open Label ◽  
Prior Therapy ◽  
Previously Treated

3021 Background: KN035 is a novel fusion protein of humanized anti-PD-L1 single domain antibody and human IgG1 Fc formulated for subcutaneous injection. This open-label phase II study evaluated the safety and antitumor activity of KN035 in patients with advanced microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) cancer. Methods: The study included patients aged ≥18 years with previously treated MSI-H/dMMR colorectal cancer (CRC) or other advanced solid tumors. MSI-H/dMMR status was assessed centrally for CRC and gastric cancer (GC) and locally for other tumors. KN035 was administered at 150 mg once weekly until progression, unacceptable toxicity, or withdrawal. Tumor assessments were every 8 weeks. The primary endpoint was the objective response rate per RECIST v1.1 by independent radiology review. The primary efficacy population (PEP) included patients with CRC who failed fluoropyrimidine (F), oxaliplatin (O), and irinotecan (I) plus those with advanced GC who had failed at least one prior systemic treatment. This was a planned interim analysis performed after the first 50 patients in the PEP had at least two on-study tumor assessments (PEPi). Results: As of December 17, 2019, 103 patients with MSI-H/dMMR advanced cancers were enrolled at 25 centers in China. The PEPi included 39 patients with CRC and 11 with GC, with a median follow-up of 7.5 months. The overall population included 65 patients with CRC (24 had prior therapy with F and O or I), 18 with GC, and 20 with other tumors, with a median follow-up of 6.7 months. The confirmed objective response rate was 30% (95% CI: 17.9%, 44.6%) in the PEPi, 54.2% (95% CI: 32.8%, 74.4%) in the CRC patients who had prior therapy with F and O or I, and 34.0% (95% CI: 24.9%, 44.0%) in the overall population. Of patients who had an objective response at the interim analysis, 80% of those in the PEPi, 84.6% of CRC patients who had prior therapy with F and O or I, and 85.7% of those in the overall population were still responding at the time of data cutoff. Median progression-free survival was 6.6 months in both the PEPi and the overall population. Median overall survival was not reached in either population. Fourteen (13.6%) patients had grade 3–4 treatment-related adverse events. No grade 5 treatment-related adverse events, pneumonitis, or colitis were reported. Local injection-site reactions, all grade 1 or 2, were reported in nine patients. Conclusions: Envafolimab demonstrated durable anti-tumor activity with a manageable safety profile in patients with previously treated advanced MSI-H/dMMR cancer. Clinical trial information: NCT03667170 .

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