Immune checkpoint inhibition (ICI) in combination with SBRT in patients with advanced pancreatic adenocarcinoma (aPDAC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 192-192 ◽  
Author(s):  
Gagandeep Brar ◽  
Changqing Xie ◽  
Charalampos S. Floudas ◽  
M. Pia Morelli ◽  
Suzanne Fioravanti ◽  
...  
Keyword(s):  
Partial Response ◽  
Locally Advanced ◽  
Primary Objective ◽  
Clinical Activity ◽  
Correlative Analysis ◽  
Progression Of Disease ◽  
New Treatment ◽  
Grade 3 ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

192 Background: Chemotherapy in aPDAC has resulted in only modest improvements in outcome. The effectiveness of ICI monotherapy is also limited in PDAC, suggesting an immunogenic inert tumor microenvironment. SBRT is safe and effective in locally advanced PDAC and exhibits enhanced antitumor immunity. We hypothesize that ICI plus SBRT will improves immunomodulatory effects of ICI in patients with aPDAC resulting in a greater clinical benefit. Methods: Eligible patients with aPDAC were enrolled to four different treatment cohorts. Cohort 1: Durvalumab (Durva) 1500 mg every 4 weeks + SBRT 1 fraction x 8Gy on day 1. Cohort 2: SBRT 5 fractions x 5Gy followed by Durva. Cohort 3: Durva + Tremelimumab (Treme) 75 mg every 4 weeks + SBRT 1 fraction x 8Gy on day 1. Cohort 4: SBRT 5 fractions x 5Gy followed by Durva + Treme. This was continued until unacceptable toxicity or progression of disease. A biopsy was performed at baseline and pre-cycle 2 of treatment for exploratory correlative analysis. The primary objective was to evaluate the safety and feasibility of combining ICI and SBRT to enhance the efficacy of ICI. Results: 51 patients with aPDAC were enrolled and 31 patients were evaluable for the efficacy. The most commonly TRAEs were lymphopenia. Grade 3-4 AEs were lymphopenia and anemia. No dose limiting toxicities were seen. Out of total 31 evaluable patients, 1 patient achieved a confirmed partial response seen in Cohort 1 and 2 patients in Cohort 4, and 7 stable disease across the 4 treatment arms. Median PFS and OS was 1.7 months (95% CI 0.7-2.8 months) and 3.4 months (95% CI 0.9-11.4 months) in cohort 1; 2.6 months (95% CI 2.1-4.7 months) and 9.1 months (95% CI 3.4-18.7 months)in cohort 2; 1.6 months (95% CI 0.5-4.0 months) and 3.0 months (95% CI 0.7-6.6 months) in cohort 3; and 3.2 months (95% CI 1.5-16.5months) and 6.4 months (95% CI 1.5-17.6 months) in cohort 4. Conclusions: The combination of ICI and SBRT is safe and well tolerated in patients with aPDAC. The overall response rate of 9.6% including 2 patients who achieved a durable partial response lasting over 12 months, suggests meaningful clinical activity. This signifies that ICI and SBRT is a potential new treatment for aPDAC. Clinical trial information: NCT02311361.

ANCHOR (OP-104): Melflufen plus dexamethasone (dex) and bortezomib (BTZ) in relapsed/refractory multiple myeloma (RRMM)—Optimal dose, updated efficacy and safety results.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8037-8037
Author(s):  
Roman Hajek ◽  
Luděk Pour ◽  
Miquel Granell ◽  
Vladimir Maisnar ◽  
Paul G. Richardson ◽  
...  
Keyword(s):  
Partial Response ◽  
Cardiac Failure ◽  
Alkylating Agents ◽  
Phase 1 ◽  
Optimal Dose ◽  
Complete Response ◽  
Primary Objective ◽  
Clinical Activity ◽  
Development Of Resistance ◽  
Grade 3

8037 Background: Development of resistance to standard treatments for RRMM highlights the need for novel therapies. Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate (PDC) that leverages aminopeptidases and rapidly releases alkylating agents inside tumor cells. Melflufen + dex showed clinical activity and an acceptable safety profile in HORIZON (Richardson et al. J Clin Oncol. 2020 Dec 9 [Epub]). This is an update of the BTZ arm of the phase 1/2a ANCHOR study (NCT03481556). Methods: Patients (pts) with RRMM were intolerant or refractory to a prior IMiD, with 1-4 prior lines of therapy (LoTs). Prior treatment with a proteasome inhibitor (PI) was allowed, but pts could not be refractory to PIs in the last LoT. Melflufen (30, 40, or 20 mg intravenously; d 1 of each 28-d cycle) was administered with BTZ (1.3 mg/m2 subcutaneous) + oral dex (20 mg on d 1, 4, 8, and 11 and 40 mg on d 15 and 22; dex dose reduced if aged ≥ 75 y). The primary objective in phase 1 was to determine the optimal phase 2 dose of melflufen for this combination. Results: As of the data cutoff date (October 19, 2020), 13 pts received melflufen (30 mg, n = 6; 40 mg, n = 7) + dex and BTZ. In the 30 mg and 40 mg cohorts, respectively, median age was 78.5 y (range, 70-82) and 70.0 y (range, 61-76); median prior LoTs was 3.5 (range, 2-4) and 2.0 (range, 1-4); 33% and 50% of evaluable pts had high-risk cytogenetics; 83% and 71% were refractory to last LoT; 100% and 86% received a prior PI; 33% and 14% were refractory to PIs. In the 30 mg and 40 mg cohorts, respectively, median treatment duration was 6.5 mo (range, 1.4-29.0) and 8.7 mo (range, 2.1-19.6); 4 (67%) and 4 pts (57%) were still on treatment; 2 and 3 pts discontinued (30 mg: progressive disease [PD] and other [1 pt each]; 40 mg: adverse event [AE], lack of efficacy, and PD [1 pt each]). Confirmed overall response rate in the 30 mg and 40 mg cohorts, respectively, was 50% (1 very good partial response [VGPR] and 2 partial response [PR]) and 71% (1 complete response, 3 VGPR, and 1 PR). Most common grade 3/4 treatment-related AEs (TRAEs) were thrombocytopenia (30 mg: 50%; 40 mg: 100%) and neutropenia (30 mg: 33%; 40 mg: 71%); grade 3/4 nonhematologic TRAEs were infrequent; 3 pts discontinued study treatment due to treatment-emergent AEs (30 mg: cardiac failure chronic and osteolysis [1 pt each]; 40 mg: thrombocytopenia [1 pt]). Serious TRAEs occurred in 2 pts (33%) in the 30 mg cohort (neutropenia and pneumonia [1 pt], syncope [1 pt]) and 1 pt (14%) in the 40 mg cohort (thrombocytopenia and neutropenia). No dose-limiting toxicities occurred at either dose level. Fatal AEs occurred in 1 pt in the 30 mg cohort (cardiac failure chronic; unrelated to study treatment). Conclusions: ANCHOR determined that the optimal dose of melflufen is 30 mg + dex and BTZ; results showed clinical activity in heavily pretreated pts. Recruitment is ongoing; updated data will be presented. Clinical trial information: NCT03481556.

Pemetrexed and carboplatin in the treatment of malignant pleural mesothelioma (MPM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18114-18114
Author(s):  
M. Papi ◽  
G. Genestreti ◽  
D. Tassinari ◽  
E. Tamburini ◽  
S. Nicoletti ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Locally Advanced ◽  
Median Number ◽  
Hematological Toxicity ◽  
Complete Regression ◽  
Progression Of Disease ◽  
Localized Disease ◽  
Grade 3 ◽  
Vitamin B12 Supplementation ◽  
Unacceptable Toxicity

18114 Background. MPM is a poor prognosis disease, whose clinical negative outcome is due both to it’s aggressiveness and to the lack of active drugs for clinical practice. To assess activity and safety of pemetrexed-carboplatin combination in the treatment of MPM, an open trial has been recently concluded in our departments. Methods. All the consecutive patients with proven diagnosis of MPM admitted to our departments between 2003 and 2005 were considered eligible and enrolled into the trial. All the patients were treated with pemetrexed 500mg/m2 and carboplatin AUC 5mg/ml/minute every 21 days until progression of disease or unacceptable toxicity. All the patients were treated with steroid prophylaxis, folinic acid and vitamin B12 supplementation. Results. 26 patients (18 chemotherapy-naive) were considered eligible and enrolled into the trial. 21 patients were male and 5 female; median age of the patients was 67 years (range 49–77). 22 patients were affected by locally advanced or extensive disease and the other 4 ones by localized disease. All the patients were valuable for response, toxicity and survival. Overall response rate was 19,3%, with 5 partial responses and no complete regression of the disease. A stable disease was observed in 7 patients (26.9%), with an overall disease control rate of 46.2%. 201 complete courses of chemotherapy was performed with a median number of 6 courses/patients. Toxicity was mild with grade 3/4 WHO neutropenia in 4 patients (15.3%), grade 3 anemia and thrombocytopenia in 2 patients (7.6%). No grade 3/4 non-hematological toxicity was observed along all the conduction of the trial. Median survival was 9,3 months, assessed with the Kaplan Meyer non-parametric test. Conclusions. Pemetrexed and carboplatin seem to represent an active and well tolerated schedule against MPM, confirming their priority role in the treatment of the disease; nevertheless, further trials are probably needed to improve the outcome of chemotherapy in this rare poor-prognosis disease. Supported by IOR No significant financial relationships to disclose.

A dose-escalation phase I study of a first-in-class cancer stemness inhibitor in patients with advanced malignancies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2542-2542 ◽  
Author(s):  
Adrian Langleben ◽  
Jeffrey G. Supko ◽  
Sebastien J. Hotte ◽  
Gerald Batist ◽  
Hal W. Hirte ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Phase 1 ◽  
Cancer Stemness ◽  
Advanced Malignancies ◽  
Progression Of Disease ◽  
Excellent Safety Profile ◽  
Grade 3 ◽  
Anti Tumor Activity ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

2542 Background: Cancer Stem Cells (CSC) are considered to be fundamentally responsible for malignant growth, relapse, metastasis, and resistance to conventional therapies. BBI608 is an orally-administered first-in-class cancer stemness inhibitor which blocks CSC self-renewal and induces cell death in CSC as well as non-stem cancer cells by inhibition of the Stat3, Nanog and b-catenin pathways, and has shown potent anti-tumor and anti-metastatic activities pre-clinically. Methods: A phase 1 dose escalation studyin adult patients with advanced cancer who had failed standard therapies was conducted to determine the safety, tolerability, recommended phase 2 dose (RP2D), pharmacokinetics and preliminary anti-tumor activity of BBI608. A modified Simon accelerated titration scheme was used for dose escalation, with a cycle consisting of twice-daily oral administration of BBI608 for 4 weeks. Cycles were repeated every 4 weeks (28 days) until progression of disease, unacceptable toxicity, or other discontinuation criteria were met. Results: Fourteen cohorts (N=41) were dosed from 20 mg to 2000 mg/day with adverse events being generally mild; the most common being grade 1-2 diarrhea, nausea, anorexia and fatigue. Four grade 3 events included diarrhea (n=3) and fatigue (n=1). MTD was not reached and further dose escalation was limited by pill burden. By the 400 mg/day dose level the plasma concentration of BBI608 was sustained for over 8 hours at a concentration above 1.5 uM (several fold above the IC50). 17/26 patients evaluable for tumor response achieved SD, for a DCR of 65%. Prolonged TTP was observed in 12/26 evaluable patients (46%), including patients with colorectal (CRC), head and neck, gastric, ovarian, melanoma, and breast cancer. In the subset of patients with CRC (N=18), SD was seen in 8/12 evaluable (67%). A median PFS of 14 weeks and median OS of 47 weeks were observed in evaluable CRC patients. Conclusions: Dose escalation of BBI608, a first-in-class cancer stem cell pathway inhibitor, has been achieved without dose limiting toxicity. BBI608 has shown an excellent safety profile, favorable pharmacokinetics, and encouraging signs of clinical activity particularly in CRC Clinical trial information: NCT01775423.

Efficacy and safety of lorlatinib in patients (pts) with ALK+ non-small cell lung cancer (NSCLC) with one or more prior ALK tyrosine kinase inhibitor (TKI): A phase I/II study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9006-9006 ◽  
Author(s):  
Alice Tsang Shaw ◽  
Sai-Hong Ignatius Ou ◽  
Enriqueta Felip ◽  
Todd Michael Bauer ◽  
Benjamin Besse ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Kinase Inhibitor ◽  
Primary Objective ◽  
Clinical Activity ◽  
Efficacy And Safety ◽  
Resistance Mutations ◽  
Small Cell Lung ◽  
Cns Metastases ◽  
Grade 3 ◽  
Clinical Trial Information

9006 Background: Lorlatinib is a selective, potent, brain-penetrant, next generation ALK/ROS1 TKI active against most known resistance mutations. In Ph I of this Ph I/II study, lorlatinib showed robust clinical activity in ALK+ or ROS1+ advanced NSCLC pts, most of whom had CNS metastases (mets) and were heavily pre-treated. In Ph II of this study, efficacy was explored based on prior ALK TKI tx as well as safety across all patients treated at the recommended Ph II dose. Methods: In this ongoing Ph II study (NCT01970865), pts with ALK+ or ROS1+ NSCLC, ± asymptomatic untreated or treated CNS mets, were enrolled into 6 expansion cohorts (EXP) based on prior tx (EXP 1-5, ALK+) and rearrangement status (EXP 6, ROS1+). Pts received lorlatinib 100mg QD. Primary objective was ORR and intracranial ORR (IC-ORR) by independent central review (ICR). Results: Efficacy (ALK+ pts with prior tx): At data cut-off (15 Aug 2016), 82 ALK+ pts were enrolled in cohorts EXP 2-5, received C1 no later than 31 Mar 2016 and were evaluated for ORR (ITT population); 52 were evaluated for IC-ORR and 35 were evaluated for IC-ORR response based on target lesions only (≥5mm; no prior radiotherapy or progression post prior radiotherapy). Confirmed response rates by ICR are reported in the table below. Safety (all pts): 116 ALK/ROS1+ pts were evaluated for safety at data cut-off. Most common tx-related AEs (TRAEs) and grade 3/4 TRAEs were hypercholesterolemia (90%, 17%) and hypertriglyceridemia (72%, 17%). Dose interruptions and reductions due to TRAEs were reported in 29% and 20% of pts, respectively. 14% of pts had tx-related SAEs. 5 pts (4%) discontinued tx due to TRAEs and there were no tx-related deaths. 74/116 pts (64%) remain on tx. Conclusions: Lorlatinib showed compelling clinical activity, with substantial IC activity, in ALK+ pts who received ≥1 prior ALK TKI, many of whom were heavily pre-treated. Clinical trial information: NCT01970865. [Table: see text]

Phase II study of ibrutinib in advanced carcinoid and pancreatic neuroendocrine tumors.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 434-434
Author(s):  
Taymeyah E. Al-Toubah ◽  
Tiffany Valone ◽  
Michael J. Schell ◽  
Jonathan R. Strosberg
Keyword(s):  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Objective Response ◽  
Prior Therapy ◽  
Progression Of Disease ◽  
Prospective Phase ◽  
Well Differentiated ◽  
Grade 3 ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

434 Background: Ibrutinib is an orally administered, inhibitor of Bruton’s tyrosine kinase (Btk). Preclinical data suggest that mast cells are recruited with neuroendocrine tumors (NETs) where they remodel the stroma and stimulate angiogenesis, driving macroscopic tumor expansion. Ibrutinib inhibits mast cell degranulation, and has been associated with regression of a mouse insulinoma model. Methods: A prospective, phase II trial evaluated patients with advanced GI/lung NETs and pNETs who had evidence of progression within 12 months of study entry on at least one prior therapy. Patients received ibrutinib 560mg daily until unacceptable toxicity, progression of disease, or withdrawal of consent. Primary endpoint was objective response rate. Results: 20 patients were enrolled on protocol from November 2015 – December 2017 (15 carcinoid and five pNETs). No patients experienced objective response. Median PFS was 3.1 months. A total of 43 drug related AEs were captured as probably or definitely associated with ibrutinib. Five patients experienced probably or definitely related grade 3 AEs and one patient experienced a probably related grade 4 AE. Five patients discontinued treatment prior to radiographic assessment. Conclusions: Ibrutinib does not show significant evidence of activity when compared to other agents (e.g. Everolimus) in well-differentiated gastroenteropancreatic and lung NETs. Clinical trial information: 02575300.

Phase II trial of pembrolizumab (MK-3475) in metastatic cutaneous squamous cell carcinoma: An updated analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21015-e21015 ◽  
Author(s):  
Melinda Lynne Yushak ◽  
David H. Lawson ◽  
Monica Goings ◽  
Marjorie Mckellar ◽  
Necia Maynard ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Stable Disease ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Primary Objective ◽  
Clinical Activity ◽  
Durable Response ◽  
Grade 3

e21015 Background: Cutaneous squamous cell carcinomas (cSCC) are generally curable with surgery and/or radiation. Unfortunately, some patients develop locally advanced or metastatic disease, with an estimated 3900 to 8700 patients dying of cSCC in 2012. Aggressive disease is often associated with immunosuppression, and no treatment has shown an improvement in overall survival (OS). Recently the FDA has approved cemiplimab-rwlc which targets PD-1. This abstract provides an updated analysis and additional followup for patients treated with pembrolizumab which also targets PD-1. Methods: Clinical activity of pembrolizumab in cSCC patients was evaluated in patients who were not curable by surgery and/or radiation. Patients were treated with pembrolizumab 200mg IV every 3 weeks for up to 2 years. Tumor response was measured every 12 weeks using RECIST version 1.1. Response rate (RR) of pembrolizumab in metastatic cSCC was the primary objective. 6-month progression-free survival (PFS) and 1 year OS were secondary objectives. Results: 11 subjects have been enrolled thus far with a median age of 70.3 years. Two were female and all were Caucasian. ORR per RECIST criteria was 64% with 18% (2) having a complete response, 36% (4) a partial response, 36% (4) progressive disease (PD), and 9% (1) stable disease. The patient with stable disease had a clinical response and was eventually able to undergo surgery that rendered him without any evidence of disease. 6 month PFS for evaluable patients was 72%. Of those patients with a response, 50% had a durable response of 18 months or greater at the time of data cut-off. No subject deaths have occurred on study. Three grade 3 related-adverse events were noted (hepatitis and pneumonitis). Conclusions: Pembrolizumab is active in advanced cSCC. Responses appear durable and comparable to what has been seen in previous studies with the FDA-approved agent, cemiplimab. No new safety concerns were noted. Additional follow up is needed in order to establish an OS benefit. Clinical trial information: NCT02964559.

ECOG 3503: A pilot study to determine if downstream markers of EGFR linked signaling pathways predict response to erlotinib (OSI-774) in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7162-7162 ◽  
Author(s):  
J. Kolesar ◽  
J. Brahmer ◽  
S. Li ◽  
P. Guaglianone ◽  
J. Patel ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Survival Data ◽  
Performance Status ◽  
Primary Objective ◽  
Disease Rate ◽  
Fish Analysis ◽  
Progression Of Disease ◽  
Grade 3 ◽  
Unacceptable Toxicity ◽  
Fixed Tumor

7162 Background: Markers of response and survival in patients (pts) who benefit from erlotinib (Elb) remain controversial. In another study, pts who developed a rash on Elb survived longer. The primary objective of this study is to prospectively identify downstream markers of EGFR linked signaling pathways that are predictive of response. The secondary objectives are to estimate response rate (RR), disease control rate, time to progression, survival, and if a grade (gr) 2 rash is a predictor of response and survival. Methods: Pts with advanced NSCLC (Stage IIIB with pleural effusion and IV, no prior systemic treatment, performance status 0–2, no symptomatic CNS metastasis, and adequate renal, hepatic and hematologic function) were accrued to this single arm study. Elb was taken orally once a day until disease progression or unacceptable toxicity. Starting at 150 mg per day, the dose was escalated by 25 mg once every 2 weeks until a gr 2 rash developed, other toxicities precluded escalation, or a maximum dose of 250 mg reached. Response was evaluated by RECIST criteria. Paraffin-fixed tumor tissue was collected on all patients for correlative studies. Results: Over 8 months, 137 pts (58 M, 79 F) were recruited with a median age of 70 (41–92). Most pts were Caucasian (92%) and had adenocarcinoma (54%). Dose escalation occurred in 53/117 of pts, with 11 getting a dose of 250mg. Only 58 pts have been evaluated for response so far. The preliminary RR is 1% (1/58) with stable disease rate of 18% (32/58). Pts have received a median of 4 cycles of treatment (range 0–10). Most pts went off trial because of progression of disease (38%, 52/137) with only 8% (11/137) stopping because of toxicities (42% unknown). Of the 123 pts evaluated for toxicity, 44 (36%) and 10 (8%) had a grade 1 / 2 and 3 rash respectively. Grade 1 / 2 diarrhea occurred in 16% (20/123) and Grade 3 diarrhea in 10% (13/123). One pt died of pneumonitis of unclear cause. Conclusions: Mature toxicity, response, and survival data as well as laboratory studies which include IHC, EGFR mutation and FISH analysis, and genotype and allele frequency will be available at the meeting. [Table: see text]

Safety, clinical activity, and PD-L1 expression of avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with metastatic urothelial carcinoma from the JAVELIN Solid Tumor phase Ib trial.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 367-367 ◽  
Author(s):  
Andrea B. Apolo ◽  
Jeffrey R. Infante ◽  
Omid Hamid ◽  
Manish R. Patel ◽  
Ding Wang ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Performance Status ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Metastatic Urothelial Carcinoma ◽  
Grade 3 ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

367 Background: Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in multiple clinical trials. We report safety and clinical activity of avelumab as a second-line therapy in patients (pts) with metastatic urothelial carcinoma (mUC) based on level of PD-L1 expression (NCT01772004). Methods: Pts with mUC unselected for PD-L1 expression received avelumab at 10 mg/kg Q2W by IV infusion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal occurred. Tumors were assessed every 6 wks (RECIST 1.1). Best overall response rate (ORR) and progression-free survival (PFS) were evaluated. Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression was assessed by immunohistochemistry. Results: As of 19 Mar 2015, 44 pts (30 men, 14 women) with mUC were treated with avelumab (median 13 wks [range 2-28]) and followed for a median of 3.5 mo (range 3.0-5.0). Median age was 68y (range 30-84), ECOG performance status was 0 (43.2%) or 1 (56.8%), and pts had received a median of 2 prior therapies (range 1- ≥ 4). Treatment-related treatment-emergent AEs (TR-TEAEs) of any grade occurred in 26 pts (59.1%); those occurring ≥ 10% were grade 1/2 infusion-related reactions (8 [18.2%]) and fatigue (7 [15.9%]). One pt had grade 3 asthenia. There were no treatment-related deaths. ORR was 15.9% (7 pts; 95% CI: 6.6, 30.1) with 1 CR and 6 PRs; 6 responses were ongoing at data cutoff. Stable disease (SD) was observed in 19 pts (42.3%) and disease-control rate (CR+PR+SD) was 59.1%. PD-L1 expression was evaluable in 32 pts. Using a ≥ 5% cutoff (10/32 [31.3%] were PD-L1+), ORR was 40.0% in PD-L1+ pts (4/10) vs 9.1% in PD-L1– pts (2/22; p= 0.060). PFS rate at 12 wks was 70.0% (95% CI: 32.9, 89.2) in PD-L1+ pts vs 45.5% (95% CI 22.7, 65.8) in PD-L1− pts. Conclusions: Avelumabshowed an acceptable safety profile and had clinical activity in pts with mUC. There was a trend towards higher ORR and prolonged PFS rate at 12 wks in pts with PD-L1+ mUC. Further analyses of PD-L1 expression and clinical activity of avelumab in UC are ongoing. *Proposed INN. Clinical trial information: NCT01772004.

Clinical outcomes according to PD-L1 status and age in the prospective international SAUL study of atezolizumab (atezo) for locally advanced or metastatic urothelial carcinoma (UC) or non-UC of the urinary tract.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4519-4519 ◽  
Author(s):  
Cora N. Sternberg ◽  
Axel Stuart Merseburger ◽  
Ernest Choy ◽  
Daniel E. Castellano ◽  
Fernando Lopez-Rios ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Median Overall Survival ◽  
Locally Advanced ◽  
Secondary Endpoints ◽  
Metastatic Urothelial Carcinoma ◽  
Grade 3 ◽  
Ecog Ps ◽  
Phase Ii And Iii ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

4519 Background: Atezo, a monoclonal antibody targeting PD-L1, is an approved therapy for locally advanced/metastatic UC based on IMvigor210 and IMvigor211 phase II and III trials. The single-arm SAUL study (NCT02928406) with a broader patient (pt) population demonstrated median overall survival (OS) of 8.7 months and a safety profile consistent with previous atezo trials. Methods: Pts with locally advanced/metastatic UC or non-UC of the urinary tract received atezo 1200 mg every 3 weeks until disease progression or unacceptable toxicity. Populations excluded from IMvigor211 (renal impairment, ECOG PS 2, treated asymptomatic CNS metastases, stable controlled autoimmune disease, concomitant steroids, HIV positive, non-UC) were eligible. The primary endpoint was safety; OS and overall response rate (ORR) were secondary endpoints. Predefined subgroup analyses included outcomes according to PD-L1 status (VENTANA SP142) and age in the overall population (and the IMvigor211-like subgroup for PD-L1). Results: Between Nov 2016 and Mar 2018, 1004 pts were enrolled; 997 received atezo. Efficacy is summarized below. Incidences of grade ≥3 treatment-related adverse events were similar irrespective of PD-L1 status (overall IC 0/1 vs 2/3: 11% vs 16%; IMvigor211-like IC 0/1 vs 2/3: 11% vs 15%) or age (≥65 y: 13%; ≥75 y: 12%; ≥80 y: 10%). Conclusions: OS and ORR appear more favorable in IC 2/3 vs IC 0/1 subgroups (overall and in the IMvigor211-like population). Atezo was effective and well tolerated across subgroups including elderly pts. Clinical trial information: NCT02928406. [Table: see text]

Interim safety and clinical activity in patients (pts) with locally advanced and unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma from a multicohort phase I study of ramucirumab (R) plus durvalumab (D).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 92-92 ◽  
Author(s):  
Yung-Jue Bang ◽  
Talia Golan ◽  
Chia-Chi Lin ◽  
Yoon-Koo Kang ◽  
Zev A. Wainberg ◽  
...  
Keyword(s):  
Phase 1 ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Primary Objective ◽  
Clinical Activity ◽  
Duration Of Treatment ◽  
Serious Adverse Event ◽  
Previously Treated ◽  
Grade 3 ◽  
Ecog Ps

92 Background: Angiogenesis and immunosuppression are hallmarks of tumor growth. This global phase 1 trial evaluates the combination of R (anti-VEGFR2) and D (anti-PD-L1) in pts with G/GEJ by simultaneously targeting these two processes. Methods: This ongoing, multi-cohort, phase 1a/b trial (NCT02572687) enrolled pts with confirmed G/GEJ adenocarcinoma with prior progression on 1 or 2 lines of systemic therapy, measurable disease, ECOG PS 0-1, and baseline tumor tissue. PD-L1 expression was assessed using the SP-263 IHC; MSI status was determined using PCR. Enrolled pts received R (8 mg/kg IV) and D (750 mg IV) every two weeks on a 28-day cycle. Primary objective was to assess safety and tolerability of R+D; preliminary efficacy was also examined. Results: As of 26-May-2017, 29 G/GEJ adenocarcinoma pts were treated. The median age was 55 y; 69% were male; 66% had ECOG PS of 1; 48% had PD-L1 ≥25% expression in tumor or immune cells, 3.5% were MSI-high; and 72% received study treatment as second line for advanced disease. Median duration of treatment was 2.5 mo for R and 3.0 mo for D. Treatment-emergent adverse events (TEAEs) occurred in 29 (100%) pts and 21 (72%) pts experienced grade 3/4 TEAEs, while treatment-related AEs (TRAE) occurred in 24 (83%) pts; none resulted in treatment discontinuation. Ten (35%) pts had grade 3 TRAEs, and no grade 4 or 5. All grade TRAEs occurring in ≥10% of pts were hypertension (34%), fatigue (31%), headache (24%), diarrhea (21%), pyrexia (10%) and decreased appetite (10%). Five pts (17%) reported a serious adverse event related to study treatment. Preliminary efficacy data (RECIST v1.1) showed 5 of 29 pts (17%) achieved a confirmed PR. Only 1 responding pt was MSI high. The overall response rate for pts with PD-L1 ≥25% was 36%. Median PFS was 2.6 mo (95% CI, 1.45 to 6.28). As of data cut-off, 6 pts (21%) remain on treatment. Conclusions: R+D generated no unexpected toxicity, and demonstrated antitumor activity in pts with previously treated advanced G/GEJ adenocarcinoma. Clinical trial information: NCT02572687.

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