Safety and activity of nivolumab monotherapy in advanced and metastatic (A/M) gastric or gastroesophageal junction cancer (GC/GEC): Results from the CheckMate-032 study.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 6-6 ◽  
Author(s):  
Dung T. Le ◽  
Johanna C. Bendell ◽  
Emiliano Calvo ◽  
Joseph W. Kim ◽  
Paolo Antonio Ascierto ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Gastroesophageal Junction Cancer ◽  
Duration Of Response

6 Background: Patients (pts) with GC/GEC often present with A/M disease, which has a poor prognosis, with 1-year survival < 30%, and few treatment options. Nivolumab is a fully human anti-PD-1 IgG4 monoclonal antibody with a favorable safety profile and efficacy in melanoma, non–small-cell lung cancer, and renal cell carcinoma. The phase I/II, open-label CheckMate-032 study evaluated nivolumab ± ipilimumab in pts with solid tumors. Here, we report initial results for pts with GEC/GC receiving nivolumab monotherapy. Methods: Pts with A/M histologically confirmed GC/GEC, irrespective of PD-L1 status, were assigned to receive nivolumab alone (3 mg/kg IV Q2W) and treated until disease progression (PD) or intolerable toxicity. The primary endpoint was objective response rate (ORR); other endpoints included safety, progression-free survival, overall survival (OS), and biomarker status. Results: 59 pts were enrolled and treated with single-agent nivolumab. Median age was 60 y (range 29–80), and 83% of pts received ≥ 2 prior regimens. At database lock, 10 pts were on active treatment; 49 pts discontinued (PD, n = 40; unrelated adverse events, n = 4; treatment-related adverse events [TRAEs], n = 2; other, n = 3). Pts received a median of 4 doses (range 1–25). ORR was 12% (n = 7/58; 1 complete response, 6 partial responses); 12 pts (21%) had stable disease. Among responders, median duration of response was 7.1 mo (95% CI, 3.0–13.2). Median OS was 6.8 mo (95% CI, 3.3–12.4); 12-mo OS rate was 38% (95% CI, 23.2–52.7). 39% of tumor samples were PD-L1 positive ( ≥ 1% cutoff). ORRs in pts with PD-L1-positive and -negative tumors were 18% and 12%, respectively. TRAEs occurred in 66% of pts; most were Grade 1/2. Grade 3/4 TRAEs occurred in 14% of pts and included pneumonitis, fatigue, diarrhea, vomiting, hypothyroidism, and increased aspartate and alanine aminotransferase and alkaline phosphatase levels. No treatment-related deaths occurred. Conclusions: Nivolumab monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated pts with GC/GEC. Objective responses occurred in pts with PD-L1-positive and -negative tumors. Clinical trial information: NCT01928394.

FIDES-01, a phase II study of derazantinib in patients with unresectable intrahepatic cholangiocarcinoma (iCCA) and FGFR2 fusions and mutations or amplifications (M/A).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS597-TPS597
Author(s):  
Milind M. Javle ◽  
Walid Labib Shaib ◽  
Stephan Braun ◽  
Marc Engelhardt ◽  
Mitesh J. Borad ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Current Status ◽  
Open Label ◽  
Open Label Phase ◽  
Duration Of Response ◽  
Symptom Response

TPS597 Background: Deregulation of the FGFR signaling pathway is implicated in various cancers. In iCCA, FGFR genetic aberrations include FGFR2 fusions and, less commonly, FGFR2 M/A. iCCA prognosis is poor, and chemotherapeutic and targeted treatment options are limited. While FGFR2 fusions are acknowledged oncogenic drivers, the oncogenic potential of FGFR2 M/A is less well defined. Derazantinib (DZB) is an investigational, oral small-molecule kinase inhibitor with activity against FGFR1, 2 and 3, which demonstrated antitumor activity in patients with unresectable iCCA with FGFR2 fusions. Based on preliminary efficacy data demonstrating durable responses of > 6 months and a clinically meaningful progression-free survival in a subset of iCCA patients harboring FGFR2 M/A (NCT01752920), the multicenter, multicohort open-label phase 2 study FIDES-01 is evaluating the effect of DZB in separate cohorts of iCCA patients with FGFR2 fusions or FGFR2 M/A. Methods: The new cohort evaluates 300 mg once daily dosing of DZB in patients with unresectable iCCA with FGFR2 M/A per liquid or tissue biopsy-based next generation sequencing and at least one previous systemic therapy. Treatment will continue until progressive disease, intolerance, withdrawal of informed consent, or death. Using a Simon’s two-stage design, the primary endpoint to assess the antitumor activity of DZB is the proportion of patients with PFS at 3 months (PFS3; per RECIST 1.1 central review). Secondary objectives are evaluation of median PFS, objective response rate, duration of response, safety profile, quality of life (incl., QLQ-C30, QLQ-BIL21, EQ-5D), and symptom response from baseline. Current status: The study was initiated in July 2019 with planned enrollment of 43 patients with confirmed FGFR2 M/A. Clinical trial information: NCT03230318.

scholarly journals HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric or gastroesophageal junction cancer: a multicenter, single-arm phase II trial

2020 ◽  
Vol 8 (2) ◽  
pp. e001279
Author(s):  
Yan Song ◽  
Ning Li ◽  
Qun Li ◽  
Xinjun Liang ◽  
Shu Zhang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Gastroesophageal Junction Cancer

BackgroundIrinotecan is used as second-line treatment in advanced gastric or gastroesophageal junction (G/GEJ) cancer. The role of anti-programmed death-1 (PD-1) antibody plus irinotecan, in this setting and population is unclear.MethodsThis multicenter, open-label, single-arm, phase II trial was conducted in 11 Chinese hospitals. Eligible patients had histologically confirmed advanced G/GEJ cancer that refractory to, or intolerant of, first-line chemotherapy with a platinum and/or fluoropyrimidine. Subjects received HX008 200 mg intravenously every 3 weeks plus irinotecan 160 mg/m2 intravenously every 2 weeks until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) as assessed according to Response Evaluation Criteria In Solid Tumors V.1.1.ResultsBetween October 2018 and September 2019, a total of 58 patients with advanced G/GEJ cancer were enrolled in this study. Median follow-up was 10.5 months (range 7.4–18.9) months. Confirmed ORR was observed in 16 patients, for an ORR of 27.6% (95% CI 16.1% to 39.1%); 19 patients experienced stable disease, leading to a disease control rate of 60.3% (95% CI 46.4% to 73.0%). ORR in patients with PD-ligand 1 (L1) positive (Combined Positive Score (CPS) ≥1) and negative (CPS＜1) tumors was 38.5% (5/13) and 37.5% (3/8), respectively. Median duration of response was 8.0 months (range 1.5–12.5), 6 of 16 (37.5%) responses were ongoing. Median progression-free survival (PFS) was 4.2 months (95% CI 2.2 to 5.5). Median overall survival (OS) was not reached (NR) (95% CI 8.7 to NR). Patients with PD-L1 positive tumors tended to have longer OS than those with PD-L1 negative tumors, but the difference was not statistically significant (NR vs 8.7 months, p=0.1858).The most common treatment-related adverse events of grade 3 or 4 included neutropenia (32.8%), leukopenia (31.0%), anemia (17.2%), decreased appetite (8.6%), vomit (6.9%), nausea (6.9%) and fatigue (5.2%). There were no treatment-related deaths.ConclusionThe combination of HX008 and irinotecan demonstrated promising activity and manageable safety as second-line treatment in patients with advanced G/GEJ cancer, which warrants further study.Trial registration numberNCT03704246

Checkmate 649: A randomized, multicenter, open-label, phase 3 study of nivolumab (Nivo) plus ipilimumab (Ipi) versus oxaliplatin plus fluoropyrimidine in patients (Pts) with previously untreated advanced or metastatic gastric (G) or gastroesophageal junction (GEJ) cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS213-TPS213 ◽  
Author(s):  
Yelena Yuriy Janjigian ◽  
Antoine Adenis ◽  
Jean-Sebastien Aucoin ◽  
Carlo Barone ◽  
Narikazu Boku ◽  
...  
Keyword(s):  
Phase 1 ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Open Label ◽  
Phase 3 ◽  
Multiple Tumor ◽  
Open Label Phase

TPS213 Background: The combination ofoxaliplatin and fluoropyrimidine is a standard-of-care (SOC) first-line treatment of pts with metastatic G/GEJ cancer, resulting in a median overall survival (OS) of 8–11 months and objective response rate (ORR) of 30%–50%. This is accompanied by up to 77% grade 3/4 toxicities. Therefore, new treatment options are needed to improve survival and decrease toxicity in G/GEJ cancer. Nivo, a fully human IgG4 monoclonal antibody (mAb) that targets programmed death 1 (PD-1) and ipi, a fully human IgG1 mAb that targets cytotoxic T-lymphocyte–associated protein 4, have demonstrated manageable safety profiles and efficacy in multiple tumor types and may have a synergistic effect. In a phase 1/2 study in chemotherapy-refractory pts with G/GEJ/esophageal cancer with or without PD-1 ligand 1 (PD-L1) expression, second-line nivo 1 mg/kg + ipi 3 mg/kg demonstrated a manageable safety profile and resulted in 26% ORR (44% ORR in pts with PD-L1+ tumors), median OS of 6.9 months, and a 34% OS rate at 12 months (Janjigian Y, et al. J Clin Oncol. 2016;34[suppl][abstract 4010]). This open-label, phase 3 trial will evaluate nivo + ipi as first-line therapy for pts with G/GEJ cancer (CheckMate 649; NCT02872116). Methods: In this study, 870 pts aged ≥ 18 years with untreated advanced or metastatic G/GEJ cancer with or without PD-L1 expression will be randomized to receive nivo + ipi (4 doses; followed by nivo monotherapy) or investigator’s choice of capecitabine/oxaliplatin (XELOX) or fluorouracil/leucovorin/oxaliplatin (FOLFOX). Tumor tissue for determination of PD-L1 status must be provided from ≤ 6 months before study treatment. Pts receiving chemotherapy or radiotherapy for G/GEJ cancer within the last 6 months or pts with suspected autoimmune disease, uncontrolled medical disorder, or active infection are excluded. Primary endpoint is OS in pts with PD-L1+ tumors. Secondary endpoints include OS in all pts and progression-free survival and time to symptom deterioration in all pts and pts with PD-L1+ tumors. Clinical trial information: NCT02872116.

scholarly journals 357 Toripalimab plus chemoradiotherapy in patients with recurrent or metastatic cervical cancer: a multicenter, open-label, single-arm, phase II trial

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A384-A384
Author(s):  
Xiaoting Xu ◽  
Jian Huan ◽  
Hui Miao ◽  
Hao Wang ◽  
Yue Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Treatment Options ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Nccn Guidelines ◽  
Significant Difference ◽  
Grade 3

BackgroundRecurrent or metastatic cervical cancer patients who progressed after standard therapy have limited treatment options and poor prognosis with a 1-year survival rate ranging between 15% and 20%. This study evaluates the efficacy and safety of toripalimab plus chemoradiotherapy in patients with recurrent or metastatic cervical cancer (Clinical trial ID: ChiCTR2000029068)MethodsIn this open-label, single-arm, phase 2 study conducted at four radiotherapy centers in East China, eligible patients were confirmed by pathology and/or imaging for recurrent or metastatic cervical cancer. According to the first-line therapies for cervical cancer recommended by NCCN guidelines, all patients were received paclitaxel plus cisplatin regimen, with or without bevacizumab, combined with radiotherapy. After seven fractions radiotherapy at the recurrent or metastatic regions, 240 mg toripalimab every three weeks for six cycles or more were given in combination.ResultsBetween Jan 14th, 2020, and May 1st, 2021, 24 patients were enrolled. All patients were staged at the first visit, as seven patients were with FIGO (2018) stage I, 10 with stage II, 2 with stage III, 1 with stage IV, and 2 with unclear stage. Of 24 included patients, 22 (91.67%) had squamous cervical cancer. The median age was 55 (range, 33–72) years. As of May 31, 2021, median follow-up time was 8.5 months [95% CI: 2.3–10.1]. 14 (58.3%) of 24 patients who achieved an objective response, including 10 (41.7%) complete response (CR) and 4 (16.7%) partial response (PR). The median duration of response was not reached and 7 (29.1%) patients continued toripalimab treatment after the previous 6-cycle immunotherapy. The disease control rate was 75% (18/24). Median progression-free survival (PFS) was 8.61 months (95% CI: 4.14–not reached). For subgroup analysis, the median PFS was significantly prolonged in the CR/PR group compared with that in the SD/PD group [not reached (95% CI: 6.21–not reached) versus 5.5 months (95% CI: 2.69–6.870), P = 0.023]. There was no significant difference in the median PFS between patients who previously received radiotherapy (8.61 months) and those who didn’t (6.87 months) (P = 0.641). 8 (33.3%) patients had grade 3–4 treatment-related adverse events (TRAEs). The most common grade 3-4 TRAEs were myelosuppression (29.2%), hypertriglyceridemia (8.3%), hypoalbuminemia (4.2%), pneumonia (4.2%), and hypercholesterolemia (4.2%).ConclusionsToripalimab plus chemoradiotherapy showed promising antitumor activity and tolerable toxicities in patients with recurrent or metastatic cervical cancer.

FRACTION (Fast Real-time Assessment of Combination Therapies in Immuno-Oncology)-gastric cancer (GC): A randomized, open-label, adaptive, phase 2 study of nivolumab in combination with other immuno-oncology (IO) agents in patients with advanced GC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4137-TPS4137 ◽  
Author(s):  
Praveen Aanur ◽  
Martin Gutierrez ◽  
Ronan Joseph Kelly ◽  
Jaffer A. Ajani ◽  
Geoffrey Yuyat Ku ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rapid Development ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
New Combination ◽  
Clinical Activity ◽  
Phase 2 ◽  
Open Label

TPS4137 Background: Nivolumab, a fully human IgG4 mAb that targets programmed death-1, alone and in combination with ipilimumab, a fully human IgG1 mAb that targets cytotoxic T-lymphocyte antigen 4, has demonstrated encouraging clinical activity in patients with advanced GC. These data support the rationale that nivolumab in combination with other IO agents or targeted therapies may improve treatment outcomes in patients with advanced GC. Given the rapid development of novel IO agents, traditional studies cannot efficiently evaluate all possible IO-IO and IO-targeted therapy combinations. FRACTION is an innovative clinical trial program with a rolling, adaptive platform design that allows for the addition of new combination regimens, as well as withdrawal of ineffective regimens. Here we describe the study concept, key design components, and the first IO treatment combinations of FRACTION-GC, a phase 2, randomized, open-label, adaptive study in advanced GC (NCT02935634). Methods: Patients with advanced GC or gastroesophageal junction (GEJ) cancer will be enrolled based on prior IO treatment and randomized to receive nivolumab plus BMS-986016 (fully human IgG4 mAb that targets lymphocyte activation gene 3) or nivolumab plus ipilimumab. Enrollment is continuous and may offer patients consecutive treatment options based on their treatment exposure and response. The primary endpoints are objective response rate, duration of response, and progression-free survival rate at 24 weeks. The secondary endpoint is safety. Comprehensive biomarker analyses will also be performed. New treatment combinations will be added over time to explore their potential benefits and to provide a continuous flow of treatment options for patients whose cancer progresses on existing treatments. In this way, FRACTION-GC is envisioned to accelerate the development of the next generation of IO combinations for patients with metastatic GC and GEJ cancer. Clinical trial information: NCT02935634.

First-line pembrolizumab (pembro) monotherapy in advanced clear cell renal cell carcinoma (ccRCC): Updated results for KEYNOTE-427 cohort A.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4570-4570 ◽  
Author(s):  
Scott S. Tykodi ◽  
Frede Donskov ◽  
Jae-Lyun Lee ◽  
Cezary Szczylik ◽  
Jahangeer Malik ◽  
...  
Keyword(s):  
Clear Cell ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Open Label ◽  
Cell Renal Cell Carcinoma ◽  
Duration Of Response ◽  
Prior Systemic Therapy

4570 Background: KEYNOTE-427 (NCT02853344) is an open-label, single-arm, phase 2 study to evaluate efficacy and safety of first-line single-agent pembro, a programmed death 1 (PD-1) inhibitor, in patients (pts) with ccRCC (cohort A) and non–clear cell RCC (cohort B). Updated follow up from cohort A are presented. Methods: Pts with histologically confirmed ccRCC, measurable per RECIST v1.1, and no prior systemic therapy were eligible. Pts received pembro 200 mg IV Q3W for 2 y or until confirmed progressive disease, unacceptable toxicity, or pt decision to withdraw. Primary end point was objective response rate (ORR; per RECIST v1.1 blinded independent central review). Additional end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: 110 pts enrolled; median (range) follow-up was 18.0 (2.5-22.7) mo. Median age (range) was 64 (29-87); 38.2%, 47.3%, and 14.5% had favorable, intermediate, and poor IMDC risk, respectively; 47.3% were PD-L1 positive. Confirmed ORR was 36.4% with 3 (2.7%) CRs and 37 (33.6%) PRs. Median DOR was not reached. Median PFS was 7.1 mo (95% CI, 5.6-11.0) and median OS was not reached. Results by IMDC category are outlined in the table. By PD-L1 status, confirmed ORR was 44.2% and 29.3% for positive and negative, respectively. By sarcomatoid differentiation (n=11), confirmed ORR was 63.6%. Treatment-related AEs occurred in 80.9%, with pruritus (28.2%) and fatigue (28.2%) most commonly reported. One pt died of treatment-related pneumonitis. Conclusions: With a median 18-months’ follow up, first-line pembro monotherapy continued to show antitumor activity in pts with ccRCC. Meaningful responses were observed in pts with intermediate/poor IMDC risk, PD-L1 positive and sarcomatoid differentiated tumors. Safety profile was comparable to previously reported. Clinical trial information: NCT02853344. [Table: see text]

Sacituzumab govitecan (IMMU-132) in patients with previously treated metastatic urothelial cancer (mUC): Results from a phase I/II study.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 354-354 ◽  
Author(s):  
Scott T. Tagawa ◽  
Bishoy Morris Faltas ◽  
Elaine Tat Lam ◽  
Philip James Saylor ◽  
Aditya Bardia ◽  
...  
Keyword(s):  
Phase I ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Complete Response ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Metastatic Urothelial Cancer

354 Background: Patients (pts) with mUC who progress after platinum (PLT)-based chemotherapy and immune checkpoint inhibitor (CPI) therapy have poor outcomes and limited treatment options. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate. It consists of a monoclonal antibody targeting Trop-2, an epithelial cell surface antigen overexpressed in UC, conjugated to the active metabolite of irinotecan (SN38). Methods: We performed a phase I/II basket study in pts with advanced solid tumors receiving intravenous SG administered on day 1 and 8 of 21-day cycles, until progression or unacceptable toxicity. CT/MRI scans were obtained at 8-week intervals for response assessment. We evaluated pts with mUC who progressed after ≥1 prior systemic therapy and were treated with SG at the 10 mg/kg dose level. Endpoints included safety, objective response rate (ORR) by RECIST 1.1, clinical benefit rate (CBR; complete response [CR], partial response [PR], or else SD ≥6-mo), and Kaplan-Meier estimated duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: 45 pts (41M/4F; median age 67, range 49-90; ECOG 0/1: 31%/69%) received a median of 2 (range: 1-6) prior treatment lines, including PLT-based chemotherapy (95%) and CPI (38%). 33 had visceral metastases involving liver (n=15), lung (n=27), and other organs (n=5). The ORR was 31% (14/45), with 2 CR and 12 PR. In pts with visceral involvement, the ORR was 27% (9/33). The ORR in CPI-treated pts was 23% (4/17). The median DOR was 12.6 mo (2 pts continuing >2 y), and the CBR was 47% (21/45). Median PFS and OS were 7.3 mo and 18.9 mo, respectively. The AE profile was consistent with prior reports. Grade ≥3 AEs in ≥5% of pts were neutropenia/neutrophil count decreased (38%), anemia (11%), hypophosphatemia (11%), diarrhea (9%), fatigue (9%), and febrile neutropenia (7%). Conclusions: SG demonstrated clinical activity in pts with relapsed/refractory mUC, including CPI-treated pts and pts with visceral disease. A single-arm, open-label, global phase 2 trial is underway to evaluate antitumor activity and safety of SG in advanced UC.(TROPHY-U-01; NCT03547973). Clinical trial information: NCT03547973.

FRACTION-RCC: Innovative, high-throughput assessment of nivolumab + ipilimumab for treatment-refractory advanced renal cell carcinoma (aRCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5007-5007 ◽  
Author(s):  
Toni K. Choueiri ◽  
Harriet M. Kluger ◽  
Saby George ◽  
Scott S. Tykodi ◽  
Timothy M. Kuzel ◽  
...  
Keyword(s):  
Partial Response ◽  
Adaptive Design ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Duration Of Response

5007 Background: The immuno-oncology (I-O) combination nivolumab + ipilimumab (NIVO+IPI) is approved for first-line (1L) and NIVO is approved for second-line treatment post TKI therapy in aRCC. The open-label, randomized, phase 2 Fast Real-Time Assessment of Combination Therapies in Immuno-Oncology (FRACTION-RCC; NCT02996110) platform study has an adaptive design allowing rapid evaluation of I-O therapies, including NIVO+IPI or other investigational combinations. This FRACTION analysis reports preliminary outcomes with NIVO+IPI in aRCC pts after progression on checkpoint inhibitor therapy. Methods: All pts, except 1, had previously received and progressed on checkpoint inhibitor treatment. Pts received NIVO+IPI (NIVO 3 mg/kg + IPI 1 mg/kg Q3W ×4, then after 6 weeks, NIVO 480 mg Q4W), up to 2 years or until progression, toxicity, or protocol-specified discontinuation. Primary endpoints were confirmed objective response rate (ORR; per investigator using RECIST v1.1), duration of response (DOR), and progression-free survival probability at week 24. Safety outcomes were reported. Results: 46 pts were randomized to NIVO+IPI. Pts had 0 (n = 1), 1 (n = 10), 2 (n = 12), 3 (n = 10), or ≥4 (n = 13) prior lines of therapy. All pretreated pts had prior anti-PD-(L)1-, none had prior anti-CTLA-4- therapy, and 37 had prior TKI-based therapy; 45 pts progressed on anti-PD-(L)1 as the most recent therapy. Most pts had clear cell aRCC (n = 44). After a median study follow-up of 8.9 months, ORR was 15.2%; no pts achieved complete response and 7 achieved partial response. DOR ranged from 2–19+ months (n = 7); 5 pts had ongoing response. Six of 7 responders had received ≥2 prior lines of therapy. Any-grade treatment-related adverse events (AEs) were reported in 36 pts (78.3%; fatigue, rash [both 19.6%], and diarrhea [17.4%] were most common). Grade 3–4 treatment-related AEs were reported in 13 pts (28.3%; diarrhea [8.7%], ↑amylase and ↑lipase [both 6.5%] were most common). Treatment-related immune-mediated AEs of any grade were reported in 22 pts (47.8%; rash [19.6%], diarrhea [17.4%], and ↑alanine aminotransferase [8.7%]). No treatment-related deaths were reported. Updated and expanded results with an additional 3 months of follow-up will be presented. Conclusions: These results suggest that NIVO+IPI may provide durable partial response in some pts with prior progression on checkpoint inhibitors, including some heavily pretreated pts. The safety profile of NIVO+IPI in FRACTION pts was similar to historic data in aRCC with this combination. Clinical trial information: NCT02996110 .

Pembrolizumab versus paclitaxel for previously treated patients with PD-L1–positive advanced gastric or gastroesophageal junction cancer (GC): Update from the phase III KEYNOTE-061 trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4503-4503 ◽  
Author(s):  
Charles S. Fuchs ◽  
Mustafa Özgüroğlu ◽  
Yung-Jue Bang ◽  
Maria Di Bartolomeo ◽  
Mario Mandalà ◽  
...  
Keyword(s):  
Standard Dose ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Analysis Data ◽  
Phase Iii ◽  
Second Line ◽  
Primary Analysis ◽  
Gastroesophageal Junction Cancer ◽  
Duration Of Response

4503 Background: KEYNOTE-061 ( NCT02370498) is a global phase 3 study of pembrolizumab vs paclitaxel as second-line therapy for GC. At the time of primary analysis (data cutoff: Oct 26, 2017), in patients with PD-L1–positive status (combined positive score [CPS] ≥1), pembrolizumab did not significantly prolong overall survival (OS) vs paclitaxel (9.1 months vs 8.3 months) but did elicit a longer duration of response (DOR) and a favorable safety profile vs paclitaxel. We present results of KEYNOTE-061 in patients with CPS ≥1, ≥5, and ≥10 after 2 additional years of follow-up (cutoff: Oct 7, 2019). Methods: Adult patients with GC that progressed after platinum + fluoropyrimidine chemotherapy were randomly assigned 1:1 to pembrolizumab 200 mg Q3W for up to 35 cycles (~2 y) or standard-dose paclitaxel. OS and progression-free survival (PFS) in the CPS ≥1 population were the primary end points. Comparisons were made using stratified log-rank tests. Results: At the time of this analysis, 366/395 patients with CPS ≥1 had died (92.6%). Pembrolizumab prolonged OS vs paclitaxel in PD-L1–positive patients (Table). No significant differences appeared between groups in PFS (Table). Objective response rate (ORR) was higher for pembrolizumab in the CPS ≥10 group, and DOR was longer with pembrolizumab using all CPS cutoffs (Table). There were fewer drug-related adverse events (AEs) with pembrolizumab than paclitaxel in the overall population (53% vs 84%). Conclusions: This long-term analysis found that second-line pembrolizumab prolonged OS among patients with PD-L1–positive GC and led to fewer drug-related AEs vs paclitaxel. Clinical trial information: NCT02370498 . [Table: see text]

Lenalidomide Oral Monotherapy Produces Durable Responses in Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

2009 ◽  
Vol 27 (32) ◽  
pp. 5404-5409 ◽  
Author(s):  
Thomas E. Witzig ◽  
Peter H. Wiernik ◽  
Timothy Moore ◽  
Craig Reeder ◽  
Craig Cole ◽  
...  
Keyword(s):  
Adverse Events ◽  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Wide Range

Purpose Lenalidomide is a novel immunomodulatory agent with antiproliferative activities. Given its efficacy in a wide range of hematologic malignancies, we conducted a phase II trial (NHL-001) of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL). Patients and Methods Patients with relapsed/refractory indolent NHL were eligible, with no limit on the number of previous therapies. Oral lenalidomide 25 mg was self-administered once daily on days 1 to 21 of every 28-day cycle for up to 52 weeks as tolerated, or until disease progression. The primary end point was objective response rate (ORR), with secondary end points of duration of response (DR), progression-free survival (PFS), and safety. Results Forty-three enrolled patients were assessable for response and safety. Patients received a median of three prior systemic therapies (range, 1 to 17) and half were refractory to last therapy. ORR was 23% (10 of 43), including a 7% complete response (CR) or unconfirmed CR rate. Twenty-seven percent (six of 22) of patients with follicular lymphoma grade 1 or 2, and 22% (four of 18) with small lymphocytic lymphoma responded to therapy. Median DR was not reached, but was longer than 16.5 months with seven of 10 responses ongoing at 15 to 28 months. Median PFS for the whole group was 4.4 months (95% CI, 2.5 to 10.4 months). Adverse events were predictable and manageable; the most common grade 3 or 4 adverse events were neutropenia (30% and 16%, respectively) and thrombocytopenia (14% and 5%, respectively). Conclusion Oral lenalidomide monotherapy produces durable responses with manageable adverse events in patients with relapsed/refractory indolent NHL, warranting further investigation of treatment for indolent NHL.

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