scholarly journals Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing

2020 ◽  
Vol 8 (1) ◽  
pp. e000775 ◽  
Author(s):  
Danny Rischin ◽  
Michael R Migden ◽  
Annette M Lim ◽  
Chrysalyne D Schmults ◽  
Nikhil I Khushalani ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Antitumor Activity ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Phase 2 ◽  
Primary Analysis ◽  
Link Type ◽  
Phase 2 Study ◽  
Group 3 ◽  
Group 1

BackgroundCemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).MethodsThe primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability.ResultsFor Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined. Per ICR, Kaplan–Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1. Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%).ConclusionIn patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses.Trial registration numberClinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498

scholarly journals Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis

2021 ◽  
Vol 9 (8) ◽  
pp. e002757
Author(s):  
Danny Rischin ◽  
Nikhil I Khushalani ◽  
Chrysalyne D Schmults ◽  
Alexander Guminski ◽  
Anne Lynn S Chang ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Squamous Cell Carcinoma ◽  
Objective Response ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Phase 2 ◽  
Kaplan Meier ◽  
Phase 2 Study ◽  
Group 3

BackgroundTo provide pooled longer term data from three groups of a phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC), and to determine duration of response (DOR) and impact on quality of life (QoL).MethodsPatients received cemiplimab 3 mg/kg every 2 weeks (group 1, metastatic CSCC [mCSCC], n=59; group 2, locally advanced CSCC, n=78) or cemiplimab 350 mg every 3 weeks (group 3, mCSCC, n=56). Primary endpoint was objective response rate (ORR) per independent central review (ICR). QoL was repeatedly measured at day 1 of each treatment cycle (groups 1 and 2: 8 weeks; group 3: 9 weeks).ResultsMedian duration of follow-up was 15.7 months. Overall, ORR per ICR was 46.1% (95% CI: 38.9% to 53.4%). Complete response (CR) rates were 20.3%, 12.8%, and 16.1% for groups 1, 2, and 3, respectively. Median time to CR was 11.2 months. Among patients with partial response or CR, the estimated proportion of patients with ongoing response at 12 months from the first objective response was 87.8% (95% CI: 78.5% to 93.3%), with median DOR not reached. Kaplan-Meier estimated probability of overall survival (OS) was 73.3% (95% CI: 66.1% to 79.2%) at 24 months, with median OS not reached. Global Health Status (GHS)/QoL improvements were observed as early as cycle 2 and were significantly improved and durable until last assessment. Kaplan-Meier estimate of median time to first clinically meaningful improvement for pain was 2.1 (95% CI: 2.0 to 3.7) months and was significantly improved in responders versus non-responders (p<0.0001).ConclusionsThis is the largest (n=193) clinical dataset for a programmed cell death-1 inhibitor against advanced CSCC, confirming the sustained substantial clinical activity of cemiplimab in these patients, including new findings of improved CR rates over time, increasing DOR, and durable pain control and GHS/QoL improvement.Trial registration numberClinicalTrials.gov Registry (NCT02760498), https://clinicaltrialsgov/ct2/show/NCT02760498.

Phase 2 study of cemiplimab, a human monoclonal anti-PD-1, in patients (pts) with metastatic cutaneous squamous cell carcinoma (mCSCC; Group 1): 12-month follow-up.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9526-9526 ◽  
Author(s):  
Alexander David Guminski ◽  
Annette May Ling Lim ◽  
Nikhil I. Khushalani ◽  
Chrysalyne D. Schmults ◽  
Leonel Fernando Hernandez-Aya ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Adverse Events ◽  
Median Duration ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase 2 ◽  
Primary Analysis ◽  
Phase 2 Study ◽  
Grade 3

9526 Background: Primary analysis (Oct 2017) of cemiplimab (REGN2810) in pts with mCSCC in a Phase 2 study demonstrated substantial antitumor activity, durable responses, and acceptable safety profile. We now report 12-month follow-up data from these pts (NCT02760498; data cutoff date: Sep 20, 2018). Methods: Pts with mCSCC received cemiplimab 3 mg/kg IV every 2 weeks (Q2W). Tumor measurements were performed Q8W. The primary objective was to evaluate objective response rate (ORR; complete response [CR] + partial response [PR]) according to independent central review (per RECIST 1.1 for scans; modified WHO criteria for photos). Results: 59 pts (median age: 71 years) were enrolled. Median duration of follow-up was 16.5 months (range: 1.1–26.6). ORR by central review was 49.2% (95% CI: 35.9–62.5; 10 CRs and 19 PRs [4 CRs and 25 PRs by investigator-assessment (INV)]). Median duration of response (DOR) has not been reached. The longest DOR at data cut-off was 21.6 months and was still ongoing. Observed DOR exceeded 12 months in 22/29 pts (75.9%) with response. Durable disease control rate (stable disease or response for ≥16 weeks) was 62.7% (95% CI: 49.1–75.0). Median observed time to response was 1.9 months (range: 1.7–9.1). Median progression-free survival was 18.4 months (95% CI: 7.3–not evaluable); median overall survival has not been reached. The most common treatment-emergent adverse events (all grades, Grade ≥3) were diarrhea (28.8%, 1.7%), fatigue (25.4%, 1.7%), and nausea (23.7%, 0%). By INV, grade ≥3 immune-related adverse events occurred in 13.6% of pts. Conclusions: This analysis demonstrates substantial antitumor activity and increasing DOR with cemiplimab 3 mg/kg Q2W in pts with mCSCC. There were no new safety signals. These data strongly support the recent FDA approval of cemiplimab-rwlc for pts with mCSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation. Clinical trial information: NCT02760498.

scholarly journals Phase 2 Study of Cemiplimab in Patients with Advanced Cutaneous Squamous Cell Carcinoma (CSCC): Longer Follow-Up

2020 ◽  
Vol 4 (6) ◽  
pp. s124
Author(s):  
Danny Rischin ◽  
Nikhil Khushalani ◽  
Chryslalyne Schmults ◽  
Alexander Guminski ◽  
Anne Lynn Chang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Phase 2 ◽  
Phase 2 Study

Abstract not available.

Tislelizumab in combination with chemotherapy in Chinese patients with advanced gastric or gastroesophageal junction (G/GEJ) cancer: Results from one cohort of an ongoing phase 2 study.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 11-11
Author(s):  
Yu-Xian Bai ◽  
En Xiao Li ◽  
Buhai Wang ◽  
Xianglin Yuan ◽  
Nong Xu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Gastroesophageal Junction ◽  
Chinese Patients ◽  
Phase 2 ◽  
First Line ◽  
Cancer Data ◽  
Cell Clearance ◽  
Phase 2 Study ◽  
Target Disease

11 Background: Tislelizumab, a humanized IgG4 mAb with high affinity and specificity for PD-1, was specifically engineered to minimize FcγR binding on macrophages, thus abrogating antibody-dependent phagocytosis, a potential mechanism of T-cell clearance and resistance to anti-PD-1 therapy. This phase 2 study (NCT03469557) evaluated safety, tolerability, and antitumor activity of first-line tislelizumab plus chemotherapy in Chinese pts with advanced G/GEJ or esophageal cancer; data from the G/GEJ cohort are presented here. Methods: Adult pts with histologically or cytologically confirmed HER2 negative G/GEJ were treated with tislelizumab (200 mg IV Q3W) + oxaliplatin (130 mg/m² IV Q3W for up to 6 cycles) + capecitabine (1000 mg/m² BID, Days 1–14 Q3W). AEs were assessed per CTCAE v4.03; tumor responses were assessed every 9 wks. Results: As of 13 June 2018, 15 G/GEJ pts (median age, 59 yr; M/F, 11/4) were enrolled; median treatment duration was 171 days (range 21-251). AEs in > 2 pts considered related to chemotherapy and/or tislelizumab are detailed in the Table. No fatal AEs occurred. Three pts discontinued treatment due to ascites or increased ALT, AST, or total bilirubin. With a median follow up of 181 days, 46.7% (n = 7) had confirmed PR, 20% (n = 3) had SD, 13.3% (n = 2) with non-target disease only at baseline had non-CR/non-PD, 6.7% (n = 1) had PD, and 13.3% (n = 2) did not have evaluable disease. ORR and DCR were 46.7% (n = 7/15) and 80% (n = 12/15), respectively. Conclusions: First-line tislelizumab plus chemotherapy was generally well tolerated and antitumor activity was observed in pts with advanced G/GEJ cancer. Clinical trial information: NCT03469557. [Table: see text]

Update on KEYNOTE-199, cohorts 1-3: Pembrolizumab (pembro) for docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 104-104 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Josep M. Piulats ◽  
Marine Gross-Goupil ◽  
Jeffrey C. Goh ◽  
Ulka N. Vaishampayan ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Response Rate ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Phase 2 Study ◽  
Previously Treated ◽  
Grade 3 ◽  
Clinical Trial Information

104 Background: The KEYNOTE-199 multicohort phase 2 study (NCT02787005) showed that pembro monotherapy has antitumor activity and acceptable safety in patients (pts) with mCRPC previously treated with a next-generation hormonal agent (NHA) and docetaxel in cohort 1 (C1) (RECIST-measurable, PD-L1+ disease), C2 (RECIST-measurable, PD-L1− disease), and C3 (bone-predominant disease, irrespective of PD-L1). Updated results with additional follow-up for C1-3 are presented. Methods: Pts previously received ≥1 NHAs and 1 or 2 chemotherapies, including docetaxel. Pts received pembro 200 mg Q3W for 35 cycles or until progression or intolerable toxicity. Primary end point was ORR. Key secondary end points were DCR, DOR, PSA (≥50%) response rate, rPFS, OS, and safety. Results: Of 258 pts enrolled (C1=133; C2=67; C3=58), 6 completed (C1=4; C3=2) and 252 discontinued (C1=129; C2=67; C3=56) therapy, primarily due to progression (C1=106; C2=61; C3=45). Median follow-up was 9.6 mo (C1, 9.5; C2, 7.9; C3, 14.2). ORR (95% CI) for pts with measurable disease was 6% (2.6-11.5) in C1 and 3% (0.4-10.4) in C2 (Table; includes other efficacy results). Treatment-related AEs of any grade/grade 3-5 occurred in 57%/16% in C1, 60%/15% in C2, and 71%/17% in C3. 1 pt in each cohort died of a treatment-related AE (C1, sepsis; C2, unknown; C3, immune-related pneumonitis). Conclusions: With additional follow-up, pembro monotherapy continued to show antitumor activity and disease control in pts with RECIST-measurable and bone-predominant mCRPC previously treated with both NHA and docetaxel. Pts experienced durable responses. Safety was consistent with the known safety profile of pembro. Clinical trial information: NCT02787005. [Table: see text]

Primary analysis of phase 2 results for cemiplimab, a human monoclonal anti-PD-1, in patients with metastatic cutaneous squamous cell carcinoma (mCSCC).

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 9519-9519 ◽  
Author(s):  
Danny Rischin ◽  
Michael Robert Migden ◽  
Anne Chang ◽  
Christine H. Chung ◽  
Lara Dunn ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Phase 2 ◽  
Primary Analysis

Primary Analysis of Phase 2 Results for Cemiplimab, a Human Monoclonal Anti-PD-1, in Patients with Metastatic Cutaneous Squamous Cell Carcinoma

2018 ◽  
Vol 2 ◽  
pp. S79
Author(s):  
Danny Rischin ◽  
Michael R Migden ◽  
Anne Lynn S Chang ◽  
Et Al.
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Phase 2 ◽  
Primary Analysis

Abstract not available. Disclosures: Study sponsored by Regeneron Pharmaceuticals and Sanofi. Copyright 2018 SKIN

scholarly journals Effects of posterior tibial slope on the mid-term results of medial unicompartmental knee arthroplasty

Arthroplasty ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Zhijie Chen ◽  
Kaizhe Chen ◽  
Yufei Yan ◽  
Jianmin Feng ◽  
Yi Wang ◽  
...  
Keyword(s):  
Knee Flexion ◽  
Tibial Slope ◽  
Posterior Tibial ◽  
Significant Difference ◽  
Medial Unicompartmental Knee Arthroplasty ◽  
Group 3 ◽  
Group 2 ◽  
Postoperative Knee ◽  
Group 1

Abstract Objective To evaluate the effect of medial posterior tibial slope (PTS) on mid-term postoperative range of motion (ROM) and functional improvement of the knee after medial unicompartmental knee arthroplasty (UKA). Methods Medical records of 113 patients who had undergone 124 medial UKAs between April 2009 through April 2014 were reviewed retrospectively. The mean follow-up lasted 7.6 years (range, 6.2–11.2 years). Collected were demographic data, including gender, age, height, weight of the patients. Anteroposterior (AP) and lateral knee radiographs of the operated knees were available in all patients. The knee function was evaluated during office follow-up or hospital stay. Meanwhile, postoperative PTS, ROM, maximal knee flexion and Hospital for Special Surgery (HSS) knee score (pre−/postoperative) of the operated side were measured and assessed. According to the size of the PTS, patients were divided into 3 groups: group 1 (<4°), group 2 (4° ~ 7°) and group 3 (>7°). The association between PTS and the knee function was investigated. Results In our cohort, the average PTS was 2.7° ± 0.6° in group 1, 5.6° ± 0.9° in group 2 and 8.7° ± 1.2° in group 3. Pairwise comparisons showed significant differences among them (p < 0.01). The average maximal flexion range of postoperative knees in each group was 112.4° ± 5.6°, 116.4° ± 7.2°, and 117.5° ± 6.1°, respectively, with significant difference found between group 1 and group 2 (p < 0.05), and between group 1 and group 3 (p < 0.05). However, the gender, age, and body mass index (BMI) did not differ between three groups and there was no significant difference between groups in terms of pre−/postoperative HSS scores or postoperative knee ROM. Conclusion A mid-term follow-up showed that an appropriate PTS (4° ~ 7°) can help improve the postoperative flexion of knee. On the other hand, too small a PTS could lead to limited postoperative knee flexion. Therefore, the PTS less than 4° should be avoided during medial UKA.

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