KEYNOTE-799: Phase 2 trial of pembrolizumab plus platinum chemotherapy and radiotherapy for unresectable, locally advanced, stage 3 NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8512-8512
Author(s):  
Salma K. Jabbour ◽  
Ki Hyeong Lee ◽  
Nicolaj Frost ◽  
Valeriy Vladimirovich Breder ◽  
Dariusz M. Kowalski ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Stage Iii ◽  
Advanced Stage ◽  
Phase 2 ◽  
Open Label ◽  
Tumor Histology ◽  
Phase 2 Trial ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
Carboplatin Auc

8512 Background: KEYNOTE-799 (NCT03631784) is an ongoing study of the anti‒PD-1 antibody pembrolizumab (pembro) plus concurrent chemoradiation therapy (cCRT) in patients (pts) with unresectable, locally advanced stage III NSCLC. Prior results from this study in a subset of pts (primary efficacy population) showed an ORR of 69.6% in cohort A (squamous and nonsquamous, n = 112) and 70.5% in cohort B (nonsquamous, n = 61), and grade ≥3 pneumonitis in 8.0% and 7.9% of pts, respectively. Here, we present results for all pts enrolled in KEYNOTE-799. Methods: This nonrandomized, multisite, open-label phase 2 trial enrolled pts aged ≥18 y with previously untreated, unresectable, pathologically confirmed, stage IIIA‒C NSCLC with measurable disease per RECIST v1.1. Pts in cohort A (squamous and nonsquamous) received 1 cycle of carboplatin AUC 6 and paclitaxel 200 mg/m2 and pembro 200 mg. After 3 wks, pts received carboplatin AUC 2 and paclitaxel 45 mg/m2 QW for 6 wks and 2 cycles of pembro 200 mg Q3W plus standard thoracic radiotherapy (TRT). Pts in cohort B (nonsquamous only) received 3 cycles of cisplatin 75 mg/m2, pemetrexed 500 mg/m2,and pembro 200 mg Q3W, and TRT in cycles 2 and 3. All pts received an additional 14 cycles of pembro 200 mg Q3W. Primary endpoints were ORR per RECIST v1.1 by blinded independent central review (BICR) and the incidence of grade ≥3 pneumonitis (per NCI CTCAE v4.0). Efficacy and safety were assessed in all pts as-treated. Results: Of 216 pts enrolled in KEYNOTE-799 (cohort A, n = 112; cohort B, n = 104), 112 in cohort A and 102 in cohort B received treatment. As of October 28, 2020, the median (range) time from first dose to database cutoff was 18.5 (13.6–23.8) mo in cohort A and 13.7 (2.9–23.5) mo in cohort B. ORR (95% CI) was 70.5% (61.2%‒78.8%) in cohort A and 70.6% (60.7%‒79.2%) in cohort B. Median DOR was not reached in either cohort (Table). ORR was similar regardless of PD-L1 status ([TPS <1% and TPS ≥1%]; Cohort A, 66.7% and 75.8%; Cohort B, 71.4% and 72.5%) and tumor histology (Cohort A, squamous, 71.2% and nonsquamous, 69.2%). Grade ≥3 pneumonitis occurred in 9 pts (8.0%) in cohort A and 7 (6.9%) in cohort B. Grade 3‒5 treatment-related AEs occurred in 72 pts (64.3%) in cohort A and 51 (50.0%) in cohort B. Conclusions: Pembro plus cCRT continues to demonstrate promising antitumor activity, regardless of PD-L1 TPS and tumor histology, and manageable safety in pts with previously untreated, locally advanced, stage III NSCLC with longer follow-up. Clinical trial information: NCT03631784. [Table: see text]

Phase II study of pembrolizumab (pembro) plus platinum doublet chemotherapy and radiotherapy as first-line therapy for unresectable, locally advanced stage III NSCLC: KEYNOTE-799.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9008-9008 ◽  
Author(s):  
Salma K. Jabbour ◽  
Ki Hyeong Lee ◽  
Nicolaj Frost ◽  
Dariusz Kowalski ◽  
Valeriy Vladimirovich Breder ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Stage Iii ◽  
Advanced Stage ◽  
Open Label ◽  
First Line Therapy ◽  
Recist 1.1 ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
Carboplatin Auc

9008 Background: KEYNOTE-799 (NCT03631784) evaluates pembro plus concurrent chemoradiation therapy (CCRT) in pts with unresectable, locally advanced stage III NSCLC. Methods: In this phase 2, nonrandomized, open-label trial, pts with previously untreated, unresectable, pathologically confirmed stage IIIA–C NSCLC with measurable disease (RECIST 1.1) received up to 17 cycles of pembro 200 mg Q3W starting with cycle 1 plus standard thoracic radiotherapy (60 Gy in 30 daily 2-Gy fractions) in cycles 2–3 and investigator’s choice of paclitaxel 200 mg/m2 + carboplatin AUC 6 Q3W for cycle 1, then paclitaxel 45 mg/m2 + carboplatin AUC 2 QW for cycles 2–3 (cohort A), or cisplatin 75 mg/m2 + pemetrexed 500 mg/m2 Q3W (nonsquamous only) in cycles 1–3 (cohort B). Primary endpoints were ORR (CR/PR per RECIST 1.1 by blinded independent central review) and rate of grade ≥3 pneumonitis (per NCI CTCAE v4.0). CIs were estimated using the Clopper-Pearson method. Safety was assessed in all treated patients; efficacy was assessed in pts with ≥15 wks follow-up. Results: As of Jan 3, 2020, 112 and 73 pts have been enrolled in cohorts A and B, respectively; 63 in cohort A and 52 in cohort B continue on treatment. Median (range) follow up was 8.3 (0.7–14.0) mo in cohort A and 5.8 (0.2–13.7) mo in cohort B. ORR (90% CI) was 67.0% (58.9%–74.3%) in cohort A and 56.6% (44.4%–68.2%) in cohort B (Table). Grade ≥3 pneumonitis occurred in 9 pts (8.0%; 90% CI, 4.3%–13.6%) in cohort A and 4 pts (5.5%; 90% CI, 1.9%–12.1%) in cohort B. Treatment-related grade ≥3 AEs occurred in 72 pts (64.3%) in cohort A and 30 pts (41.1%) in cohort B. 4 pts had treatment-related grade 5 pneumonitis (all in cohort A). Enrollment is complete for cohort A and ongoing in cohort B. Conclusions: Pembro plus CCRT shows promising antitumor activity in pts with unresectable, locally advanced stage III NSCLC. Toxicity was as anticipated with pembro plus CCRT. Clinical trial information: NCT03631784. [Table: see text]

Phase 2 trial of first-line pembrolizumab with platinum doublet chemotherapy and radiotherapy in patients (pts) with unresectable, locally advanced stage III non–small-cell lung cancer (NSCLC): KEYNOTE-799.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS8575-TPS8575 ◽  
Author(s):  
Salma K. Jabbour ◽  
Keunchil Park ◽  
Dosinda Cohn ◽  
Hong Liu ◽  
Steven M. Keller ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Stage Iii ◽  
Clinical Activity ◽  
Advanced Stage ◽  
Phase 2 ◽  
First Line ◽  
Recist 1.1 ◽  
Stage Iii Nsclc ◽  
Doublet Chemotherapy ◽  
Platinum Doublet

TPS8575 Background: Standard therapy for pts with unresectable stage III NSCLC is concurrent platinum doublet chemotherapy with radiotherapy (CCRT); however, this therapy does not reduce the risk of distant relapse, and the 5-y survival rate is low. The anti–PD-1 checkpoint inhibitor pembrolizumab has durable clinical activity as first-line therapy for advanced/metastatic NSCLC: as monotherapy for PD-L1–positive tumors and in combination with chemotherapy irrespective of PD-L1 status. KEYNOTE-799 evaluates the safety/efficacy of first-line pembrolizumab plus CCRT for unresectable, locally advanced stage III NSCLC. Methods: This nonrandomized, open-label phase 2 study enrolls pts ≥18 y with previously untreated, unresectable, pathologically confirmed stage IIIA–C NSCLC with measurable disease per RECIST 1.1. Pts receive 17 cycles of pembrolizumab 200 mg Q3W plus standard thoracic radiotherapy in cycles 2 and 3 (60 Gy in 30 daily 2 Gy fractions). In cycles 1–3, treatment also includes investigator’s choice of either paclitaxel 200 mg/m2 and carboplatin area under the curve (AUC) 6 Q3W for 1 cycle, followed by paclitaxel 45 mg/m2 and carboplatin AUC 2 weekly for 6 weeks, or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 Q3W (nonsquamous only). Tumor imaging occurs at baseline and Q9W until week 54, verified PD, initiation of new cancer therapy, study withdrawal, or death. AEs are graded by NCI CTCAE v4.0. Primary endpoints are the rate of grade ≥3 pneumonitis and ORR (RECIST 1.1 by blinded independent central review [BICR]); confidence intervals for both will be estimated by the Clopper-Pearson method. Secondary endpoints are PFS (RECIST 1.1 modified to follow ≤10 target lesions; ≤5 per organ by BICR), OS, and safety. PFS and OS will be analyzed by Kaplan-Meier method. Approximately 216 pts (108 per cohort) will be enrolled in 59 sites in 10 countries beginning on Nov 5, 2018. As of Feb 12, 2019, 30 pts have enrolled. Continuous interim analyses using binomial sequential testing will be performed after ≥36 pts have ≥15 weeks of follow up in each cohort, to allow earlier treatment discontinuation, if required. Clinical trial information: NCT03631784.

Nilotinib in locally advanced pigmented villonodular synovitis: a multicentre, open-label, single-arm, phase 2 trial

2018 ◽  
Vol 19 (5) ◽  
pp. 639-648 ◽  
Author(s):  
Hans Gelderblom ◽  
Claire Cropet ◽  
Christine Chevreau ◽  
Richard Boyle ◽  
Martin Tattersall ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Pigmented Villonodular Synovitis ◽  
Villonodular Synovitis ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Pigmented Villonodular

Observed survival benefit with limited exposure of durvalumab in unresectable stage III non-small cell lung cancer at a large community-based institution.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20539-e20539
Author(s):  
Deepak Vadehra ◽  
Christopher R Pallas ◽  
Donald Moore ◽  
Jeryl Jean Villadolid ◽  
Myra M. Robinson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Benefit ◽  
Locally Advanced ◽  
Small Cell ◽  
Stage Iii ◽  
Advanced Stage ◽  
Small Cell Lung ◽  
Fda Approval ◽  
The Pacific ◽  
Stage Iii Nsclc

e20539 Background: The PACIFIC trial ushered in a paradigm shift in the management of unresectable, non-metastatic non-small cell lung cancer (NSCLC), demonstrating improvement in 12,24,36-month overall survival (OS) and leading to the 2018 FDA approval for durvalumab in unresectable or locally advanced stage III NSCLC. With almost 3 years of FDA approval, we performed a retrospective analysis of patient experiences and outcomes at Levine Cancer Institute analyzing patient data to assess survival and potential points of clinical significance. Methods: Patients over the age of 18, who met criteria similar to the PACIFIC trial (i.e. unresectable or locally advanced stage III NSCLC) from February 2018 through September 2020 were analyzed. Those who were receiving active treatment at the data cutoff were excluded. Patient characteristics, prior treatment, durvalumab administration, immune-related adverse events (irAEs), and efficacy data were summarized and evaluated. OS and progression free survival (PFS) were evaluated with Kaplan Meier methods. Results: A total of 159 patients were evaluated. 40.9% were female and 59.1% were male. The median age was 67 (range 38-83 years). Of note, 86.8% of patients were white, whereas 13.2% were nonwhite. 50.3% patients experienced an irAE. The most common reasons for discontinuation of durvalumab were completion (at least 24 doses), progressive disease, or toxicity (33.3%, 30.8%, 26.4%, respectively). The median number of doses of durvalumab received was 14 (range 1-26 doses). The median PFS was 15.3 months with 12-and 24-month PFS being 54% and 41.1 %, respectively. Median OS was 42 months with 12-and 24-month OS being 78.1% and 67.8%, respectively. Our analysis compared outcomes in those who completed adjuvant durvalumab versus those who did not complete adjuvant therapy (Table). Conclusions: Data shows the best survival in those who completed durvalumab (comparable to historic values) and novel data shows a perceived survival benefit in those completing 12 doses compared to those who did not. Thus, partial treatment may provide a survival advantage. Further multivariate analysis will look for possible correlations to increased immune events and inability to complete therapy. Further investigation will delve into this cohort’s small proportion of non-white patients, evaluating for possible barriers to care that may lead to more patients being diagnosed with stage IV NSCLC.[Table: see text]

Phase I study of capecitabine combined with weekly carboplatin and intensity modulated radiation therapy (IMRT) for treatment of locally advanced squamous cell carcinomas of the head and neck (HNSCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15522-15522
Author(s):  
C. Y. Thomas ◽  
P. Read ◽  
K. Sheng ◽  
D. Bliesner ◽  
P. Levine ◽  
...  
Keyword(s):  
Phase I ◽  
Locally Advanced ◽  
Intensity Modulated Radiation Therapy ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Stage Iii ◽  
Fixed Dose ◽  
Parotid Sparing ◽  
Grade 3 ◽  
Carboplatin Auc

15522 Background: Chemoradiotherapy (CRT) programs for locally advanced HNSCC that reduce toxicity but maintain efficacy are needed. Methods: A two-step phase I trial to determine the maximum tolerated dose (MTD) of capecitabine combined with fixed dose carboplatin, given prior to and during concomitant IMRT. Start dose of capecitabine =1500 mg/m2/d p.o. BID days 1–14 and 22–35 with carboplatin AUC =2 IV weekly x 6. With IMRT, the doses were adjusted to 1000 mg/m2/d and AUC =1.5, respectively. Parotid-sparing IMRT = 50 and 45 Gy/25 fractions to gross disease (GD) and low risk nodes, respectively; 3D conformal boost of 20 Gy/10 fractions to GD. Dose limiting toxicity (DLT) defined as ANC <750, ≥ grade 3/4 thrombocytopenia or selected non-hematologic toxicities. Results: 11 patients (pts) with stage III/IV (T2–4,N1–2C) HNSCCs of the oropharynx (7), oral cavity (2), both (1), or hypopharynx (1) were studied. 10/9 pts evaluable for toxicity after induction/concomitant chemotherapy, respectively; 2 pts had early disease progression (d22 and 43). During radiation, the MTD for capecitabine established as 825 mg/m2/d. At start dose, 2/3 pts developed thrombocytopenia as DLT; CRT-related toxicities = grade 3 mucositis (3), dysphagia (3), fatigue (1), anemia (1), and dermatitis (1). For induction chemotherapy, DLTs seen in 0/3 pts at capecitabine =1750 mg/m2 and 1/6 at lower doses (grade 4 diarrhea; no other Gr3/4 drug-related toxicities). Response of primary (or neck) tumors to induction: CR 3 (3), PR 6 (3), SD 1 (3), and PD 2 (2). After CRT, 8/9 pts achieved CR and are alive without disease (mean follow-up 6 months). Conclusions: Capecitabine 825 mg/ m2/d and carboplatin AUC =1.5 weekly given on the described schedule and in combination with IMRT produce moderate toxicity and a high complete response rate in stage III/IV HNSCC pts that received the same drugs as induction therapy. The latter combination was also well tolerated and had anti-tumor activity (capecitabine Y=1500–1750 mg/m2/d). Additional studies are warranted to determine if these regimens provide an effective but less toxic alternative to cisplatin or taxane-based CRT programs. Supported in part by Bristol-Myers-Squibb. No significant financial relationships to disclose.

Safety study of induction chemotherapy and synchronous radiotherapy (RT) and cetuximab in stage III non-small cell lung cancer (NSCLC): SCRATCH (Cohort I)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18032-18032 ◽  
Author(s):  
S. R. Hughes ◽  
J. L. Liong ◽  
A. Miah ◽  
S. Ahmad ◽  
M. Leslie ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Initial Dose ◽  
Performance Status ◽  
Locally Advanced ◽  
Skin Toxicity ◽  
Stage Iii ◽  
Study Cohort ◽  
Neck Carcinoma ◽  
Stage Iii Nsclc ◽  
Grade 3

18032 Background: The addition of cetuximab can increase the efficacy of chemotherapy for advanced NSCLC. Concomitant cetuximab and RT is superior to RT alone for locally advanced squamous cell head & neck carcinoma. The SCRATCH study (cohort I) is a phase I study to assess the safety of synchronous cetuximab and radical RT in patients with Stage III NSCLC. Methods: Cohort I will contain 12 patients with inoperable stage III NSCLC. Inclusion criteria are performance status 0–1, adequate organ function, and disease encompassable within a radical RT volume. Exclusion criteria are previous malignancy, thoracic RT or treatment with EGFR targeted therapy. Patients receive platinum-based induction chemotherapy, followed by weekly intravenous cetuximab (initial dose 400mg/m2; maintenance dose 250mg/m2) and concomitant RT (64Gy/32fractions/45days). The primary end-point is toxicity. NCI Common Toxicity Criteria (CTC) V3.0 assessments are performed weekly during radiotherapy, and at regular follow-up visits. Results: Data from the first 9 patients is available. 2 patients stopped receiving cetuximab early due to toxicity. 1 experienced grade 3 fatigue following the initial dose, and the other declined further treatment after developing grade 2 skin toxicity. 2 patients have died, 1 from disease progression and 1 from thromboembolic disease. Both deaths occurred between months 2 and 4 post RT and were not attributed to the cetuximab therapy. Of the 7 living patients, 2 have survived 1 year (measured from the first day of induction chemotherapy). The maximum NCI CTC V3.0 scores are summarised in the table below. Conclusions: The results suggest that the early and late toxicities of synchronous cetuximab and radical RT are acceptable. Data on all 12 patients will be available by June 2007. SCRATCH Study cohorts II-IV follow on and will recruit sequentially. They will assess the safety of adding concomitant cisplatin (±vinorelbine) to cetuximab and radical RT. [Table: see text] No significant financial relationships to disclose.

TROPHY-u-01: A phase II open-label study of sacituzumab govitecan (IMMU-132) in patients with advanced urothelial cancer after progression on platinum-based chemotherapy and/or anti-PD-1/PD-L1 checkpoint inhibitor therapy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS495-TPS495 ◽  
Author(s):  
Scott T. Tagawa ◽  
Daniel Peter Petrylak ◽  
Petros Grivas ◽  
Neeraj Agarwal ◽  
Cora N. Sternberg ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Checkpoint Inhibitor ◽  
Objective Response ◽  
Locally Advanced ◽  
Low Grade ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy

TPS495 Background: Patients (pts) with unresectable locally advanced or metastatic urothelial cancer (mUC) who progress after platinum-based chemotherapy and checkpoint inhibitor (CPI) therapy and pts ineligible for platinum-based chemotherapy who progress after CPI have limited treatment options and poor outcomes. Trop-2 is an epithelial cell surface antigen that is overexpressed in UC. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate that targets Trop-2 and delivers the active metabolite (SN38) of the topoisomerase I inhibitor irinotecan to tumor cells. In a phase 1/2 single-arm trial, pts with advanced cancers received SG 10 mg/kg intravenously on days 1 and 8 of a 21-day cycle; preliminary results in the cohort of 41 evaluable pts with mUC and a median of 3 (range 1–6) prior therapies showed an objective response rate (ORR) of 34%. Adverse events (AE) were mostly low grade, including diarrhea (63%), nausea (56%), and fatigue (49%). Neutropenia (all grades) occurred in 49% of pts (≥ grade 3/4, 39%; treatment-related serious AE of febrile neutropenia, 5%). Median overall survival was 16.1 months, and median progression-free survival was 7.1 months. These results warrant further investigation in a dedicated phase 2 trial. Methods: TROPHY-U-01 is a single-arm, open-label, global phase 2 trial evaluating the antitumor activity and safety of SG in 140 pts with advanced UC. The primary cohort (progression after platinum chemotherapy and CPI) will enroll 100 pts in a Simon 2-stage design with > 90% power accounting for dropouts to exclude the null hypothesis or ORR < 12%, while a second cohort (40 pts) will comprise cisplatin-ineligible pts who received prior CPI. The primary objective is ORR per RECIST 1.1, assessed by central review. Secondary objectives include response duration, PFS, OS, and safety/tolerability. Enrollment began in August 2018. Clinical trial information: NCT03547973.

scholarly journals Concurrent chemoradiotherapy with cisplatin/vinorelbine and cisplatin/docetaxel in locally advanced stage III NSCLC

2015 ◽  
Vol 26 ◽  
pp. vii124
Author(s):  
Makoto Nagamata ◽  
Yusuke Okuma ◽  
Kuniko Sunami ◽  
Kageaki Watanabe ◽  
Satoshi Takahashi ◽  
...  
Keyword(s):  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Stage Iii ◽  
Advanced Stage ◽  
Stage Iii Nsclc
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