scholarly journals Safety and tolerability of andecaliximab as monotherapy and in combination with an anti-PD-1 antibody in Japanese patients with gastric or gastroesophageal junction adenocarcinoma: a phase 1b study

2022 ◽  
Vol 10 (1) ◽  
pp. e003518
Author(s):  
Akie Kimura Yoshikawa ◽  
Kensei Yamaguchi ◽  
Kei Muro ◽  
Atsuo Takashima ◽  
Takashi Ichimura ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Her2 Status ◽  
Clinical Activity ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Programmed Death 1 ◽  
Phase 1B

BackgroundMatrix metalloproteinase 9 (MMP9) is implicated in protumorigenic processes. Targeting either stromal or epithelial MMP9 reduces the incidence of metastasis. Andecaliximab is a monoclonal antibody that targets MMP9 with high affinity and selectivity. However, no study has examined whether the inhibition of T-cell programmed death 1 (PD-1) in the presence of andecaliximab increases activated lymphocyte infiltration into the tumor, thereby increasing antitumor activity more than that in anti-PD-1 monotherapy. In this study, we assessed the safety, pharmacokinetics (PK), exploratory biomarkers, and preliminary efficacy of andecaliximab as monotherapy and in combination with nivolumab in Japanese patients with advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma.MethodsThis phase 1b study comprised four cohorts enrolling Japanese patients with gastric or GEJ adenocarcinoma. This paper concerns cohorts 1 and 4; cohorts 2 and 3 will be reported subsequently. Cohort 1 enrolled patients with human epidermal growth factor receptor 2 (HER2)-negative tumors (n=8) who received andecaliximab monotherapy (800 mg by intravenous infusion every 2 weeks (Q2W)), and cohort 4 enrolled patients irrespective of their HER2 status (n=10) who received 800 mg of andecaliximab in combination with nivolumab Q2W. Safety, dose-limiting toxicities (DLTs), PK, pharmacodynamics, and biomarkers were assessed in both cohorts.ResultsPK of andecaliximab in Japanese patients with gastric or GEJ adenocarcinoma was similar to that reported in non-Japanese patients with advanced solid tumors. Andecaliximab monotherapy and in combination with nivolumab demonstrated no DLTs in cohort 1 and 4, respectively. Toxicities were manageable and well tolerated in both cohorts. The median progression-free survival was 1.4 months (90% CI, 0.5 to 5.4) and 4.6 months (90% CI, 0.9 to not reached) in cohorts 1 and 4, respectively. The objective response rate was 50% (90% CI, 22% to 78%) in cohort 4, and in some patients, the combination therapy was effective regardless of the biomarker status.ConclusionsThe andecaliximab–nivolumab combination demonstrated a manageable safety profile and promising clinical activity in patients with advanced gastric adenocarcinoma.NCT02862535.

A phase Ib/II, multicenter, open-label, dose-escalation, and dose-expansion study evaluating trastuzumab deruxtecan (T-DXd, DS-8201) monotherapy and combinations in patients with HER2-overexpressing gastric cancer (DESTINY-Gastric03).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS261-TPS261
Author(s):  
Yelena Y. Janjigian ◽  
Natasha Viglianti ◽  
Feng Liu ◽  
Ariadna Mendoza-Naranjo ◽  
Liz Croydon
Keyword(s):  
Gastric Cancer ◽  
Dose Escalation ◽  
Topoisomerase I ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Metastatic Gastric Cancer ◽  
Her2 Status ◽  
Open Label ◽  
Phase 1B

TPS261 Background: For patients (pts) with HER2-overexpressing metastatic gastric cancer, trastuzumab + chemotherapy is a standard first-line option but provides only a modest overall survival (OS) benefit vs chemotherapy. T-DXd is an antibody-drug conjugate consisting of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and a membrane-permeable topoisomerase I inhibitor payload. Results from a phase 1 trial showed promising antitumor activity (confirmed objective response rate [ORR], 43.2%) in pts with heavily pretreated HER2+ metastatic gastric cancer who received T-DXd (5.4 or 6.4 mg/kg; Shitara K, et al. Lancet Oncol. 2019;20:827-836). Here we describe the phase 1b/2 DESTINY-Gastric03 trial (NCT04379596) evaluating T-DXd monotherapy and combinations in pts with HER2-overexpressing gastric cancer. Methods: This is an open-label, multicenter, 2-part, phase 1b/2 study in pts with HER2-overexpressing (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization positive) locally advanced, unresectable or metastatic gastric or gastroesophageal junction cancer. In part 1 (dose escalation), pts who had received prior trastuzumab-containing therapy will be assigned to 1 of 5 arms: (1) T-DXd + 5-fluorouracil (5-FU); (2) T-DXd + capecitabine (C); (3) T-DXd + durvalumab; (4) T-DXd + 5-FU or C + oxaliplatin (Ox); or (5) T-DXd + 5-FU or C + durvalumab. In part 2 (dose expansion), pts with no prior treatment for metastatic disease will be randomized across 4 arms: (1) T-DXd; (2) trastuzumab + 5-FU or C + Ox or cisplatin; (3) T-DXd + 5-FU or C ± Ox; or (4) T-DXd + 5-FU or C + durvalumab. In part 2, pts will be stratified by HER2 status. Primary endpoints are safety, determination of recommended phase 2 doses (part 1), and investigator-assessed confirmed ORR per RECIST v1.1 (part 2). Secondary endpoints include confirmed ORR (part 1), disease control rate, duration of response, progression-free survival (all per investigator), OS, safety (part 2), pharmacokinetics, and immunogenicity. Clinical trial information: NCT04379596.

Results of the JAVELIN Gastric 100 phase 3 trial: avelumab maintenance following first-line (1L) chemotherapy (CTx) vs continuation of CTx for HER2− advanced gastric or gastroesophageal junction cancer (GC/GEJC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 278-278 ◽  
Author(s):  
Markus H. Moehler ◽  
Mikhail Dvorkin ◽  
Mustafa Ozguroglu ◽  
Min-hee Ryu ◽  
Alina Simona Muntean ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Clinical Activity ◽  
Primary Analysis ◽  
Open Label ◽  
Phase 3 ◽  
Post Induction

278 Background: We report the primary analysis of JAVELIN Gastric 100, which compared avelumab (anti–PD-L1) maintenance after 1L CTx vs continued CTx in patients (pts) with GC/GEJC. Methods: In this global, open-label, phase 3 trial (NCT02625610), eligible pts had previously untreated, unresectable, locally advanced/metastatic (LA/M) HER2− GC/GEJC. Pts without progressive disease (PD) after 12 weeks of 1L oxaliplatin/fluoropyrimidine induction were randomized 1:1 to avelumab 10 mg/kg Q2W switch maintenance or continued CTx, stratified by region (Asia vs non-Asia). Primary endpoint was overall survival (OS) post induction in all randomized or PD-L1+ (≥1% of tumor cells, 73-10 assay) pts. Results: 805 pts received induction CTx and 499 pts were randomized (avelumab, n = 249; CTx, n = 250). At data cutoff (Sep 13, 2019), minimum follow-up was 18 months. In the avelumab and CTx arms, median OS post induction/randomization was 10.4 months (95% CI 9.1-12.0) vs 10.9 months (95% CI 9.6-12.4), hazard ratio (HR) 0.91 (95% CI 0.74-1.11; p = 0.1779); 24-month OS rates were 22.1% (95% CI 16.8-28.0) vs 15.5% (95% CI 10.8-20.9), respectively. The HR for OS in PD-L1+ pts (n = 54) was 1.13 (95% CI 0.57-2.23). No OS trend was seen in Asian pts (n = 114; HR 0.90 [95% CI 0.59-1.36]) or other subgroups, except for a potential benefit with avelumab in pts with no metastatic sites at randomization (n = 60; HR 0.52 [95% CI 0.28-0.98]). Progression-free survival was similar between arms (HR 1.04 [95% CI 0.85-1.28]). In the avelumab vs CTx arms, objective response rates (post randomization only) were 13.3% (95% CI 9.3-18.1) vs 14.4% (95% CI 10.3-19.4), and 12-month rates for duration of response were 62.3% (95% CI 40.9-77.9) vs 28.4% (95% CI 13.2-45.7), respectively. Treatment-related adverse event rates (all grades/grade ≥3) were 61.3%/12.8% with avelumab and 77.3%/32.8% with CTx. Conclusions: Avelumab maintenance showed clinical activity and favorable safety vs continued CTx in pts with LA/M GE/GEJC; however, JAVELIN Gastric 100 did not meet its primary objective of demonstrating superior OS in the randomized or PD-L1+ population. Clinical trial information: NCT02625610.

Ramucirumab and paclitaxel in patients with gastric cancer and prior trastuzumab: subgroup analysis from RAINBOW study

2019 ◽  
Vol 15 (23) ◽  
pp. 2723-2731 ◽  
Author(s):  
Ferdinando De Vita ◽  
Christophe Borg ◽  
Gabriella Farina ◽  
Ravit Geva ◽  
Iris Carton ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Subgroup Analysis ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Combination Group ◽  
Clinical Trial Registration ◽  
Trastuzumab Therapy ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Registration Number

Aim: This subgroup analysis of the RAINBOW study evaluated the efficacy and safety of ramucirumab in patients with gastric cancer/gastroesophageal junction adenocarcinoma who received prior trastuzumab therapy. Patients & methods: Of adult patients enrolled in the RAINBOW study, 39 had received prior trastuzumab therapy. Of these, 20 patients were treated with ramucirumab plus paclitaxel and 19 patients with placebo plus paclitaxel within the RAINBOW trial. Results: Overall survival was longer with ramucirumab plus paclitaxel (11.4 months; 95% CI: 7.0–17.9) versus placebo plus paclitaxel (7.0 months; 95% CI: 3.4–14.6), hazard ratio: 0.68 (0.33–1.41); p = 0.30. Longer progression-free survival, higher objective response were observed in ramucirumab combination group. Conclusion: Ramucirumab plus paclitaxel demonstrated efficacy benefits with manageable safety profile in a subgroup of patients pretreated with trastuzumab.Clinical trial registration number: NCT01170663.

Modified FOLFOX versus modified FOLFOX plus nivolumab and ipilimumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction: Moonlight, a randomized phase 2 trial of the German Gastric Group of the AIO.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4144-TPS4144 ◽  
Author(s):  
Salah-Eddin Al-Batran ◽  
Claudia Pauligk ◽  
Thorsten Oliver Goetze ◽  
Jorge Riera-Knorrenschild ◽  
Eray Goekkurt ◽  
...  
Keyword(s):  
Type I Error ◽  
Checkpoint Inhibitors ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Rank Test ◽  
Clinical Activity ◽  
Type I ◽  
First Line

TPS4144 Background: The majority of patients (pts) with gastroesophageal cancer present with inoperable or metastatic disease and there is a strong need for efficient and tolerable first-line (1L) treatment. Oxaliplatin-based regimens like FOLFOX have become one standard of care. However, median survival is still below 12 months. Results from trials using nivolumab plus ipilimumab treatment of subjects with advanced/metastatic GC and GEJ cancers demonstrated clinical activity, in pts whose tumors did or did not express PD-L1; in addition, nivolumab alone and in combination with ipilimumab demonstrated clinical benefits in various other tumor types. Based on this clinical experience, the AIO-STO-0417 trial (Moonlight) has been designed to evaluate the combination of chemotherapy with two checkpoint inhibitors in first-line therapy of pts with gastroesophageal adenocarcinoma. Methods: This is a prospective, multicenter, randomized, investigator-initiated phase II trial. Pts with Her2-negative, inoperable, advanced or metastatic gastric or esophagogastric junction cancer will be randomized 1:1 to 1L treatment with FOLFOX (Oxaliplatin 85 mg/m²; Leucovorin 400 mg/m²; 5FU 400 mg/m² on d1 of each treatment cycle and 5FU 1200 mg/m² continuous infusion over 24 hrs d1 and d2) every 2 weeks plus Nivolumab 240 mg every 2 weeks and Ipilimumab 1mg/kg every 6 weeks (Arm A) or FOLFOX alone (Arm B). Primary endpoint of the trial is progression-free survival based on the ITT population. Main secondary endpoints are overall survival, objective response rate, Safety and Quality of life (EORTC QLQ-C30). 118 pts (59 per arm) will be enrolled to provide 80% power for detecting an average HR of 0.68 using the log rank test at a one-sided type I error of 10%. At the date of submission, (Feb 2019), 28 of planned 118 pts are randomized. Clinical trial information: NCT03647969.

KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 228-228
Author(s):  
Hope Elizabeth Uronis ◽  
Christel Rushing ◽  
Gerard C. Blobe ◽  
Shiaowen David Hsu ◽  
Niharika B. Mettu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
First Line ◽  
Tumor Biopsy ◽  
Gastroesophageal Junction Adenocarcinoma

228 Background: Gastric and esophageal adenocarcinomas are a leading cause of cancer death worldwide. Many of these patients (pts) present with locally advanced unresectable or metastatic disease and are treated with combination cytotoxic chemotherapy. Single agent P is FDA approved for patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (GEJ) whose tumors have a combined positive score (CPS) ≥ 1 after disease progression on or after two lines of therapy including fluoropyrimidine and platinum and her2/neu-targeted therapy (if indicated). More effective therapy is needed earlier in the disease trajectory. We conducted a single-arm phase II trial to establish the safety and efficacy of first-line C and O + P. Methods: Pts with previously untreated metastatic GE adenocarcinoma regardless of PDL-1 status received intravenous (IV) P 200mg with IV O 130mg/m2 every three weeks and oral C 850mg/m2 twice daily for 14 days on/7 days off. After the 6 patient safety cohort, pts first completed a biomarker cycle that included fresh tumor biopsy before P and one week after P before chemotherapy started. Archived FFPE tumor samples were also obtained from all pts with available tissue. The primary endpoint was progression free survival (PFS); secondary endpoints included response rate (RR) and overall survival (OS). Results: 36 pts were enrolled and 34 pts were evaluable for efficacy (1 pt withdrew for personal reasons before end of cycle 1 and 1 pt had immune-related toxicity during cycle 1 and was taken off study before any efficacy assessment). 9 pts (26%) had an esophageal primary, 18 pts (53%) had a GEJ primary and 7 pts (21%) had a gastric primary. Median PFS was 7.6 months [95% CI: 5.8 to 12.2], RR was 72.7% [95% CI: 57% to 88%], and median OS was 15.8 months [95% CI: 11.6 to NE]. 27 patients (81.8%) had decrease in disease burden (ranging from -19% to -100%). After > 18 months of follow-up, 5 patients remained in durable complete response (CR). Immune-mediated treatment related adverse events (TRAEs) included thyroid disorders (n=5; 14%), colitis (n=4; 11%), adrenal insufficiency (n=2; 5%), and type 1 diabetes (n=1). Sixteen patients (44%) experienced grade 3 or 4 TRAEs. There were no grade 5 TRAEs. Conclusions: The combination of C and O + P had acceptable safety and significant clinical activity. These promising results indicate that C and O + P merits further study as a first line option for patients with unresectable locally advanced or metastatic GE adenocarcinoma. Updated survival and correlative data will be presented. Clinical trial information: NCT03342937.

scholarly journals Apatinib in treating clinical and biochemical recurrent ovarian cancer

2019 ◽  
Author(s):  
Zhongyu Wang ◽  
Yake Huang ◽  
Ling Long ◽  
Li Zhou ◽  
Yan Huang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Chemotherapeutic Agents ◽  
Ca 125 ◽  
Clinical Activity ◽  
Clinical Relapse ◽  
Biochemical Relapse

Abstract Background: Apatinib, a small molecule inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), exerts antiangiogenic effects. Taken orally, apatinib shows clinical activity in the treatment of recurrent or platinum-resistant ovarian cancer (OC) as monotherapy or in combination with other chemotherapeutic agents. We investigated the efficacy of apatinib in recurrent OC and preliminarily evaluated the clinical activity of apatinib in biochemical-only recurrent OC patients. Results: We retrospectively analyzed clinical material of 41 recurrent patients who had received apatinib monotherapy or apatinib plus chemotherapy between June 2016 and August 2018. Apatinib was administered at a 500 mg daily dose. Response was determined according to measurable disease or serum carbohydrate antigen (CA)-125 levels. Progression-free survival (PFS) was estimated by Kaplan-Meier method. All patients were evaluable, 19 (46.34%) had biochemical relapse and 22 (53.66%) had clinical relapse. The objective response rate (ORR) and disease control rate (DCR) in the overall population were 31.71% and 78.05%, respectively. The median PFS was 7 months (95% confidence interval 5.43-8.57). In patients with biochemical relapse only, the median PFS was 6 months, with ORR of 26.32% and DCR of 89.47%. Conclusions: Apatinib is a well-tolerated and effective agent in patients with recurrent OC and has the potential to delay clinical progression in patients with asymptomatic biochemical relapse.

Safety, PD-L1 expression, and clinical activity of avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with advanced gastric or gastroesophageal junction cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 167-167 ◽  
Author(s):  
Hyun Cheol Chung ◽  
Hendrik-Tobias Arkenau ◽  
Lucjan Wyrwicz ◽  
Do-Youn Oh ◽  
Keun-Wook Lee ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Clinical Activity ◽  
Prior Therapy ◽  
Gastroesophageal Junction Cancer ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Disease Stabilization ◽  
Phase Iii Trials

167 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. We report safety and clinical activity of avelumab in patients (pts) with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJ) based on level of PD-L1 expression. This phase Ib JAVELIN study (NCT01772004) enrolled pts who had progressed on prior therapy ( ≥ 2L) and pts who had received 1L chemotherapy but had not yet progressed (switch-maintenance [Mn]) Methods: Pts received avelumab 10 mg/kg Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumours were assessed every 6 wks (RECIST 1.1). Best overall response and progression-free survival (PFS) were evaluated. Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression was assessed by immunohistochemistry using various cutoff criteria Results: As of Feb 13, 2015, 75 pts with GC/GEJ were treated with avelumab (20 pts, 2L; 55 pts, Mn). Treatment-related treatment-emergent AEs (TR-TEAEs) of any grade occurred in 47 pts (62.7%); the most common ( > 10%) was infusion-related reaction (12 [16.0%], all grade 1/2). Nine pts (12.0%) reported a grade ≥ 3 TR-TEAE, including fatigue (2), thrombocytopenia (2), and anemia (2; each 2.7%). There was 1 treatment-related death (hepatic failure/autoimmune hepatitis). Responses were observed in 7 pts (3/20 2L, all PRs; 4/55 Mn, 1 CR, 3 PRs). PD-L1 expression was evaluable in 55 pts (12/20 2L, 43/55 Mn), including in 3 pts with a response. Median PFS in 2L group was 36.0 wks (95% CI: 6.0, 36.0) for PD-L1+ and 11.6 wks (2.1, 21.9) for PD-L1− ( ≥ 1% cutoff). In Mn group, median PFS for PD-L1+ and PD-L1− status was 17.6 wks (5.9, 18.0) and 11.6 wks (5.7, 17.7), respectively ( ≥ 1% cutoff). Conclusions: Single agent avelumab showed an acceptable safety profile and clinical activity in GC/GEJ pts. Objective responses and disease stabilization were observed in both groups. Median PFS was longer in PD-L1+ pts. Phase III trials in 1L and 3L GC/GEJ are underway.*Proposed INN Clinical trial information: NCT01772004.

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.

Avelumab in patients with metastatic urothelial carcinoma: Pooled results from two cohorts of the phase 1b JAVELIN Solid Tumor trial.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 330-330 ◽  
Author(s):  
Manish R. Patel ◽  
John Allan Ellerton ◽  
Jeffrey R. Infante ◽  
Manish Agrawal ◽  
Michael S. Gordon ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Clinical Activity ◽  
Best Response ◽  
Metastatic Urothelial Carcinoma ◽  
Phase 1B ◽  
Grade 3

330 Background: Avelumab is a fully human anti‒PD-L1 IgG1 antibody with promising efficacy and safety in patients (pts) with metastatic urothelial carcinoma (mUC). To further characterize the clinical activity of avelumab in mUC, we report a planned interim pooled analysis of 2 cohorts from a large phase 1b trial (NCT01772004). Methods: Pts with mUC progressed after platinum-based therapy or cisplatin-ineligible, and unselected for tumor PD-L1 expression, received avelumab 10 mg/kg (1 h IV) Q2W. Response was assessed every 6 wks by independent review per RECIST v1.1. Endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety (NCI CTCAE v4.0), and tumor PD-L1 expression (clone 73-10). Results: As of Mar 19, 2016, 241 pts received avelumab for a median of 8 wks (range 2-80); median follow-up was 7.3 mos (range 0-18.2). Primary tumor sites were upper tract (renal pelvis/ureter [23.7%]) and lower tract (bladder/urethra [76.3%]). 95.4% of pts had progressed on prior platinum therapy, and 63.4% had received ≥ 2 prior lines for advanced disease (range 0-6). In 153 pts with ≥ 6 mos follow-up, confirmed ORR was 17.6% (95% CI 12.0-24.6) with 9 complete responses and 18 partial responses; 24/27 (88.9%) were ongoing. Median DOR was not reached, and the 24-wk DOR rate was 92.0% (95% CI 71.6, 97.9). 36 pts had stable disease as best response (disease control rate 41.2%). Median PFS was 6.4 wks (95% CI 6.1-11.4), and median OS was 7.0 mos (95% CI 5.6-11.1). Based on a ≥ 5% PD-L1 staining cutoff in evaluable pts with PD-L1+ (n = 56) and PD-L1– (n = 75) tumors, ORR was 25.0% (95% CI 14.4-38.4) vs 14.7% (95% CI 7.6-24.7; p = 0.178). Treatment-related adverse events (TRAE) of any grade occurring in ≥ 10% of pts were infusion-related reaction (22.8%) and fatigue (12.0%). 7.5% had a grade ≥ 3 TRAE; fatigue (1.2%)/asthenia (0.8%) occurred in > 1 pt. 28 pts (11.6%) had an immune-related TRAE (grade ≥ 3 in 2.5%). There was 1 treatment-related death (pneumonitis). Conclusions: Avelumab is well tolerated and shows promising clinical activity, including durable responses, in pts with mUC, regardless of tumor PD-L1 expression status. Follow-up is ongoing. Clinical trial information: NCT01772004.

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