An open label, nonrandomized, multi-arm, phase II trial evaluating pembrolizumab combined with cetuximab in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Results of cohort 1 interim analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6033-6033 ◽  
Author(s):  
Assuntina Gesualda Sacco ◽  
Ruifeng Chen ◽  
Debanjali Ghosh ◽  
Deborah J.L. Wong ◽  
Francis P. Worden ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Stable Disease ◽  
Interim Analysis ◽  
Safety Data ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Response Duration ◽  
Dual Therapy ◽  
Open Label ◽  
Platinum Refractory

6033 Background: Pembrolizumab (a humanized monoclonal antibody blocking programmed death receptor-1[PD-1]), and cetuximab (a chimeric monoclonal antibody inhibiting epidermal growth factor receptor) are both FDA-approved, second-line monotherapies for R/M HNSCC. This is the first trial to evaluate anti-tumor efficacy of dual therapy with pembrolizumab and cetuximab. Previously reported safety data demonstrated favorable toxicity. An interim futility analysis of cohort 1 (anti-PD-1/PD-L1 and cetuximab naïve) was completed per protocol. Methods: Patients (pts) with platinum-refractory/ineligible, R/M HNSCC were treated with pembrolizumab 200mg IV on day 1 and cetuximab 400mg/m2 loading dose followed by 250mg/m2 weekly (21-day cycle). Primary endpoint: overall response rate (complete and partial responses) by 6 months (mo). Secondary endpoints: 12-mo progression-free survival (PFS) probability, overall survival, response duration, safety, correlative analyses. Results: 14 evaluable pts were enrolled March 2017-October 2018. Median age 60y (range 47-86y), M:F 6:8, ECOG (0:1) 2:12, 14 mucosal primaries (9 oral cavity, 2 HPV-mediated oropharynx, 2 non-EBV-associated nasopharynx, 1 larynx). 11 pts (79%) had no prior lines of systemic therapy for R/M HNSCC (range 0-1). 6 pts (42.8%) had a partial response by 6 months, meeting pre-planned criteria for trial continuation. 4 pts (28.6%) had stable disease and 4 (28.6%) had progressive disease. Median PFS was 128 days (4.3 mo). Median duration of response was 160.5 days (5.4 mo) for partial responders and 133 days (4.4 mo) for pts with stable disease. Disease control rate (partial + stable) was 71.4%. There were 7 grade 3 treatment-related toxicities. 2 pts discontinued cetuximab due to toxicity, however, both continued pembrolizumab. Conclusions: Interim analysis indicates that pembrolizumab plus cetuximab is potentially active for platinum-refractory/ineligible pts with R/M HNSCC. These results meet protocol specifications for trial continuation. Final results will include PD-L1 expression data. Clinical trial information: NCT03082534.

Panitumumab antitumor activity in patients (pts) with metastatic colorectal cancer (mCRC) expressing ≥ 10% epidermal growth factor receptor (EGFr)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3548-3548 ◽  
Author(s):  
J. Berlin ◽  
M. Neubauer ◽  
P. Swanson ◽  
W. G. Harker ◽  
H. Burris ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Interim Analysis ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Response Duration ◽  
Expression Levels ◽  
Prior Therapy ◽  
Tumor Expression

3548 Background: Panitumumab is a fully human monoclonal antibody directed against EGFr. We investigated panitumumab antitumor activity in pts who failed prior therapy and had EGFr tumor expression levels ≥ 10%. Methods: In this multicenter, phase 2 study of 300 planned pts, pts had documentation of disease progression (PD) during or following adequate doses of fluoropyrimidine, irinotecan, and oxaliplatin (centrally confirmed refractory disease [CCRD]), 2–3 prior regimens, ECOG score 0–2, and EGFr staining (by IHC) in ≥ 10% of evaluable tumor cells. Pts received panitumumab at 6 mg/kg Q2W until PD. Tumor assessments (modified WHO, blinded central review) were taken periodically from wk 8–48 until PD. Study endpoints were objective response rate (ORR) at wk 16 (+ ≥ 4 wk confirmation; primary) and ORR throughout study, response duration, progression-free survival (PFS) time, survival time, and safety (secondary). Results: In this interim analysis (5/05), 91 enrolled pts received ≥ 1 dose of panitumumab (safety set); 39 had ≥ 20 wks before the cutoff and CCRD (efficacy set). The efficacy set consisted of 23M/16W, mean (SD) age of 58.6 (10.1) years, 82% white, 95% ECOG ≤ 1, 74% colon cancer and 26% rectal cancer; all had ≥ 2 prior regimens (equivalent characteristics for safety set). At wk 16, 3 (8%) had a partial response, 8 (21%) had stable disease, and 19 (49%) had PD as best OR (9 not done/unevaluable). At the time of this interim analysis, response durations were 12.4, 13.2, and 14.0 wks. In the safety set, 96% had at least 1 treatment-related adverse event (24% grade [gr] 3, 1% gr 4, 1% gr 5). Integument and eye toxicities were: 96% skin, 30% nail, 8% eye, 5% hair, and 7% chelitis. 25 (27%) had diarrhea (3 gr 3); 11 (12%) had hypomagnesemia (3 gr 3/4). One pt had a gr 3 hypersensitivity reaction considered related to panitumumab, received medication, and the event resolved; this pt continued treatment with premedication; no further reactions occurred. In 66 pts with both a baseline and postdose sample, no human anti-human antibodies to panitumumab were detected.Additional data will be presented. Conclusions: Panitumumab has antitumor activity and is well tolerated in pts with EGFr tumor expression levels ≥ 10% who failed standard chemotherapy. [Table: see text]

scholarly journals ACTR-33. INFIGRATINIB (BGJ398) IN PATIENTS WITH RECURRENT GLIOMAS WITH FIBROBLAST GROWTH FACTOR RECEPTOR (FGFR) ALTERATIONS: A MULTICENTER PHASE II STUDY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi20-vi20
Author(s):  
Andrew Lassman ◽  
Juan Sepúlveda-Sánchez ◽  
Timothy Cloughesy ◽  
Juan Gil-Gil ◽  
Vinay Puduvalli ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Stable Disease ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Genetic Alterations ◽  
Open Label

Abstract INTRODUCTION FGFR mutations and translocations occur in approximately 10% of glioblastomas (GBMs). FGFR3-TACC3 fusion is predictive of response to FGFR tyrosine kinase inhibitors pre-clinically and clinically. Infigratinib (BGJ398) is a selective small-molecule pan-FGFR kinase inhibitor with anti-tumor activity in several solid tumors with FGFR genetic alterations. METHODS Open-label phase II trial of adults with recurrent high-grade gliomas following failure of initial therapy (NCT01975701). Tumors harbored FGFR1-TACC1 or FGFR3-TACC3 fusions, activating mutations in FGFR1, 2 or 3, or FGFR1, 2, 3, or 4 amplification. Oral infigratinib was administered 125 mg d1–21 q28d. Prophylaxis for hyperphosphatemia was recommended. Primary endpoint: 6-month progression-free survival (6mPFS) rate by RANO (locally assessed); goal of >40%. RESULTS As of Sep 2017, 26 patients (16 men, 10 women; median age 55 years, range 20–76 years; 50% with ≥ 2 prior regimens) were treated; 24 (92.3%) discontinued for disease progression (n=21) or other reasons (n=3). All had FGFR1 or FGFR3 gene alterations; 4 had >1 gene alteration. Estimated 6mPFS rate was 16% (95% CI 5.0–32.5%); median PFS was 1.7 months (95% CI 1.1–2.8 months); median OS was 6.7 months (95% CI 4.2–11.7 months); ORR was 7.7% (95% CI 1.0–25.1%). Best overall response was: partial response 7.7% (FGFR1 mutation n=1; FGFR3 amplification n=1); stable disease 26.9%; progressive disease 50.0%; missing/unknown 15.3%. Most common (>15%) all-grade treatment-related adverse events (AEs) were hyperphosphatemia, fatigue, diarrhea, hyperlipasemia, and stomatitis. There were no grade 4 treatment-related AEs. Eleven patients (42.3%) had treatment-related AEs requiring dose interruptions/reductions (most commonly hyperphosphatemia). CONCLUSIONS Infigratinib induced partial response or stable disease in approximately one-third of patients with recurrent GBM and/or other glioma subtypes harboring FGFR alterations. Most AEs were reversible and manageable. Further potential combinations are being explored in patients with proven FGFR-TACC fusion genes; analysis of biomarker data is ongoing.

A phase II trial of bevacizumab in patients with recurrent solid tumor brain metastases who have failed whole brain radiation therapy (WBRT).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2070-2070
Author(s):  
Priya Kumthekar ◽  
Karan Dixit ◽  
Sean Aaron Grimm ◽  
Rimas Vincas Lukas ◽  
Margaret A. Schwartz ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Solid Tumor ◽  
Stable Disease ◽  
Treatment Options ◽  
Thrombotic Event ◽  
Progression Free Survival ◽  
Response Duration ◽  
Response Assessment ◽  
Open Label

2070 Background: Brain metastases (BM) are the most common intracranial malignancy with overall a poor prognosis estimated at approximately 4 months from time of initial diagnosis for treated patients, and even lower after failing WBRT after which treatment options have been limited and outcomes poor. Methods: This is an open label phase 2 study where patients who have previously failed WBRT received bevacizumab at a dose of 10 mg/kg intravenously every two weeks until CNS disease progression with one cycle being defined as 4 weeks. The primary endpoint was objective radiographic tumor response as defined by modified Response Assessment in Neuro-oncology (RANO) criteria. Secondary endpoints included progression free survival (PFS) at 6 months, time to progression, time to response, duration of response, overall survival (OS), quality of life (QOL) as measured by the FACT-G and FACT-Br and safety. Results: A total of 27 patients were consented and registered to study of which 24 were evaluable for ORR (3 came off study prior to first follow up MRI brain). Medianage was 53 (range 27-73), median number of cycles was 5.5 (range 1-20) with a median follow up of 8.7 months (range 2.4-47.9mo). Of the 24evaluable patients, there were 6 Partial response, 16 stable disease and 2progressive disease. The 6 month PFS: 46% (95% CI: 25% - 67%) and median PFS was 5.3 months. Median OS was 9.5 months (95% confidence interval 6.3m – 15.0m). For the patients who completed sequential QOL assessments, there was no significant decline in QOL but there was a nonsignificant improvement in the FACT-Br scores. Overall, treatment was well tolerated with 3grade 3 adverse events seen: hypertension (n = 3), headache (n = 1) and thrombotic event (n = 1). Conclusions: For this WBRT failure BM population, we were able to show a 25% disease response to bevacizumab therapy along with good drug tolerability and no noted central nervous system bleeding. Improved survival as compared to historical controls was seen 9.5 m. Of the 24 evaluable patients, 81% (22/24) experienced clinical benefit defined as stable disease or better. Bevacizumab therapy could be a viable option for solid tumor BM patients who experience progression following WBRT, however a larger trial is required to confirm this data. Clinical trial information: NCT01898130.

scholarly journals An Expanded Treatment Protocol of Panobinostat Plus Bortezomib and Dexamethasone in Patients with Previously Treated Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3027-3027
Author(s):  
Vincent L Hansen ◽  
Morton Coleman ◽  
Stephanie Elkins ◽  
Jeffrey P. Letzer ◽  
Moshe Yair Levy ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Stable Disease ◽  
Safety Data ◽  
Treatment Protocol ◽  
Treatment Phase ◽  
Progression Free Survival ◽  
Open Label ◽  
Phase 3 ◽  
Advisory Committees ◽  
Grade 3

Abstract Introduction: Panobinostat (PAN) is a potent pan-deacetylase inhibitor that targets multiple myeloma (MM) cells via its effects on epigenetics and protein metabolism. In the PANORAMA 1 phase 3 trial, the combination of PAN, bortezomib (BTZ), and dexamethasone (Dex; PAN-BTZ-Dex) significantly increased progression-free survival compared with placebo plus BTZ and Dex, leading to US Food and Drug Administration approval of the combination for the treatment of patients with MM who have received ≥ 2 prior regimens including BTZ and an immunomodulatory agent. The "PANobinostat EXpansion treatment protocol" (PANEX) study was developed to provide access to PAN and gather additional safety data on the PAN-BTZ-Dex combination until PAN became commercially available. Methods: PANEX is a multicenter, open-label, expanded treatment protocol study of PAN-BTZ-Dex in adult patients with MM relapsed and/or refractory to ≥ 1 prior line of therapy. During treatment phase (TP) 1 of the study, patients received oral PAN (20 mg; days 1, 3, 5, 8, 10, and 12) plus intravenous (IV) or subcutaneous (SC) BTZ (1.3 mg/m2; days 1, 4, 8, and 11) for eight 21-day cycles. Patients with at least stable disease proceeded to TP2, with maintained PAN and less frequent BTZ dosing (days 1 and 8) for an additional 8 cycles. In both phases, oral Dex (20 mg) was administered on the days of and after BTZ treatment. Reduction to once-weekly BTZ was allowed before TP2 as a dose reduction strategy. Response assessments were completed per modified European Group for Blood and Marrow Transplantation criteria. Results: A total of 39 patients, with a median age of 70 years (range, 44-88 years), were enrolled in the study. Patients were heavily pretreated, with a median of 3 prior lines of therapy (range, 1-12; 21% ≥ 7 prior therapies), with nearly half of the patients (48.7%) having progressed on their most recent therapy. Most patients received SC BTZ (87.2% [n = 34] vs 12.8% [n = 5] IV BTZ), with a median treatment duration of 9.4 weeks (range, 2-34). A total of 21 patients achieved a partial response, leading to an overall response rate of 53.8%; an additional 17.9% achieved a minimal response, for a clinical benefit rate (≥ minimal response) of 71.8%, with 25.6% having stable disease. Notably, no patients in the current trial had a best response of progressive disease. The most common grade 3/4 hematologic laboratory abnormalities were thrombocytopenia (53.8%), anemia (17.9%), and neutropenia (17.9%). The most common nonhematologic grade 3/4 treatment-emergent adverse events (AEs) were dehydration (28.2%), fatigue (28.2%), diarrhea (17.9%), asthenia (10.3%), and pneumonia (10.3%). Common gastrointestinal treatment-emergent AEs of any grade included diarrhea (48.7%), nausea (25.6%), and vomiting (12.8%), and nearly all cases of dehydration were associated with these gastrointestinal events. Interestingly, in the patients receiving SC BTZ (n = 34), the rate of grade 3/4 diarrhea was 11.8%, approximately half the rate seen with IV BTZ administration in the phase 3 PANORAMA 1 trial (25%). Common serious AEs included dehydration (15.4%), diarrhea (12.8%), and pneumonia (10.3%). AEs led to PAN, BTZ, and Dex dose reductions in 59.0%, 59.0%, and 46.2% of patients, respectively. Conclusions: Overall, the results from PANEX, albeit in an older population of patients with more advanced MM, support those generated in PANORAMA 1. In the subgroup of patients receiving SC BTZ, the rate of diarrhea, an AE of interest with PAN-BTZ-Dex therapy, appeared to be reduced when compared with PANORAMA 1 data with IV BTZ administration. Further clinical experience with the use of SC BTZ in this combination will help to determine the potential impact of route of BTZ administration on tolerability. Disclosures Elkins: Pharmacyclics/Janssen: Speakers Bureau; Onyx Pharmaceuticals: Speakers Bureau. Letzer:Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Speakers Bureau. Levy:Takeda: Consultancy. Seneviratne:Novartis: Honoraria, Speakers Bureau. Rine:Novartis: Employment. White:Novartis: Employment. Kuriakose:Novartis: Employment, Equity Ownership.

Efficacy and safety of bevacizumab in combination with irinotecan and infusional 5-FU as first-line treatment for patients with metastatic colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3544-3544 ◽  
Author(s):  
A. Sobrero ◽  
S. Ackland ◽  
R. P. Carrion ◽  
S. Chiara ◽  
S. Clarke ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Safety Data ◽  
Progression Free Survival ◽  
Response Duration ◽  
Primary Objective ◽  
Efficacy And Safety ◽  
First Line ◽  
Open Label ◽  
Chemotherapy Administration

3544 Background: Bevacizumab is a monoclonal antibody that, by inhibiting VEGF, inhibits tumour angiogenesis. It has been proven to improve overall (OS) and progression-free survival (PFS) when administered first-line in combination with the bolus 5-FU-based IFL regimen to patients with metastatic colorectal cancer [Hurwitz et al. NEJM 2004;350:2335–42]. We have conducted a multicentre, open-label trial to further evaluate the efficacy and safety of first-line bevacizumab in combination with regimens combining irinotecan with infusional 5-FU (FOLFIRI). Methods: Eligible patients had: metastatic colorectal cancer; no surgery within 28 days; no prior chemotherapy for metastatic disease; ECOG PS 0/1; adequate organ function; no CNS metastases. Chemotherapy consisted of 6 cycles of irinotecan plus infusional 5-FU and leucovorin, according to the classical FOLFIRI regimen; however, such variations as the simplified FOLFIRI or the weekly regimen were allowed. Bevacizumab 5mg/kg was given on day 1 of chemotherapy, every 2 weeks until disease progression. Safety assessments were made at the time of chemotherapy administration during the first 12 weeks and every 4 weeks thereafter. Tumour assessments were performed every 3 months for the first year and 4-monthly thereafter. The primary objective was PFS; secondary objectives were to evaluate the safety profile of this combination as well as to determine the overall response rate, time to response, duration of response and OS. Results: A total of 209 patients were enrolled at 31 centres in Australia, Canada, Italy, Spain and China between April 2005 and November 2005. 60% of patients were male and median age was 61.9 (range 31–82) years. All patients will be eligible for interim analysis, that will be performed after the last patient enrolled has been followed for a minimum of 12 weeks (6 cycles of chemotherapy), in February 2006. Data on safety and efficacy from this analysis will be presented. Conclusions: This is the largest clinical trial that will report efficacy and safety data for bevacizumab in combination with an irinotecan and infusional 5-FU regimen. [Table: see text]

scholarly journals OS10.6 Infigratinib (BGJ398) in patients with recurrent gliomas with fibroblast growth factor receptor (FGFR) alterations: a multicenter phase II study

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii21-iii22 ◽  
Author(s):  
A B Lassman ◽  
J M Sepúlveda-Sánchez ◽  
T Cloughesy ◽  
J M Gil-Gil ◽  
V K Puduvalli ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Stable Disease ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Genetic Alterations ◽  
Open Label ◽  
Recurrent Gbm

Abstract BACKGROUND FGFR mutations and translocations occur in approximately 10% of glioblastomas (GBMs). FGFR3-TACC3 fusion has been reported as predictive of response to FGFR tyrosine kinase inhibitor therapy both pre-clinically and clinically. Infigratinib (BGJ398) is a selective small-molecule pan-FGFR kinase inhibitor that has demonstrated anti-tumor activity in several solid tumors with FGFR genetic alterations. Therefore, we conducted a phase II trial to test the efficacy of infigratinib in FGFR-altered recurrent GBM (NCT01975701). METHODS This open-label trial accrued adults with recurrent high-grade gliomas following failure of initial therapy that harbored FGFR1-TACC1 or FGFR3-TACC3 fusions; activating mutations in FGFR1, 2 or 3; or FGFR1, 2, 3, or 4 amplification. Oral infigratinib was administered 125 mg on days 1–21 every 28 days. Prophylaxis for hyperphosphatemia, a common toxicity, was recommended. The primary endpoint was the 6-month progression-free survival (6mPFS) rate by RANO (locally assessed, estimated by K-M method), with a goal of >40%. RESULTS As of the Sep 2017 data cut-off, 26 patients (16 men, 10 women; median age 55 years, range 20–76 years; 50% with ≥2 prior regimens) were treated, and 24 (92.3%) discontinued for disease progression (n=21) or other reasons (n=3). All patients had FGFR1 or FGFR3 gene alterations, and 4 had >1 gene alteration. The estimated 6mPFS rate was 16% (95% CI 5.0–32.5%); median PFS was 1.7 months (95% CI 1.1–2.8 months); median OS was 6.7 months (95% CI 4.2–11.7 months); ORR was 7.7% (95% CI 1.0–25.1%). The best overall response was: partial response 7.7% (FGFR1 mutation n=1; FGFR3 amplification n=1); stable disease 26.9%; progressive disease 50.0%; missing/unknown 15.3%. The most common (>15%) all-grade treatment-related adverse events (AEs) were hyperphosphatemia, fatigue, diarrhea, hyperlipasemia, and stomatitis. There were no grade 4 treatment-related AEs. Eleven patients (42.3%) had treatment-related AEs requiring dose interruptions or reductions (most commonly hyperphosphatemia). CONCLUSIONS Infigratinib induced partial response or stable disease in approximately one-third of patients with recurrent GBM and/or other glioma subtypes harboring FGFR alterations. Most AEs were reversible and manageable. Further potential combinations are being explored in patients with proven FGFR-TACC fusion genes and analysis of biomarker data is ongoing.

Daratumumab (DARA) maintenance or observation (OBS) after treatment with bortezomib, thalidomide and dexamethasone (VTd) with or without DARA and autologous stem cell transplant (ASCT) in patients (pts) with newly diagnosed multiple myeloma (NDMM): CASSIOPEIA Part 2.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8004-8004
Author(s):  
Philippe Moreau ◽  
Pieter Sonneveld ◽  
Keyword(s):  
Interim Analysis ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Second Primary ◽  
Cell Transplant ◽  
Open Label ◽  
Depth Of Response

8004 Background: D-VTd plus ASCT was approved for transplant-eligible (TE) NDMM based on part 1 of CASSIOPEIA. We report a prespecified interim analysis of CASSIOPEIA part 2: DARA maintenance vs OBS in pts with ≥partial response (PR) in part 1, regardless of induction/consolidation (ind/cons) treatment. Methods: CASSIOPEIA is a 2-part, randomized, open-label, phase 3 study in TE NDMM. Pts received 4 cycles ind and 2 cycles cons with D-VTd or VTd. 886 pts who achieved ≥PR were rerandomized to DARA 16 mg/kg IV Q8W for up to 2 yr (n = 442) or OBS (n = 444) until progressive disease per IMWG. Pts were stratified by ind (D-VTd vs VTd) and depth of response (minimum residual disease [MRD] status and post cons response ≥PR). Primary endpoint was progression-free survival (PFS) after second randomization. This interim analysis assessed efficacy and safety after 281 PFS events. A preplanned hierarchical procedure tested key secondary endpoints: time to progression (TTP), ≥complete response (CR), MRD negativity rates by NGS and overall survival (OS). Results: At median follow-up of 35.4 mo, median PFS was not reached (NR) with DARA and 46.7 mo with OBS (HR 0.53; 95% CI 0.42–0.68; P <0.0001). PFS advantage for DARA was consistent across most subgroups. However, a prespecified analysis showed significant interaction with ind/cons treatment arm ( P< 0.0001). PFS HR for DARA vs OBS was 0.32 (95% CI 0.23–0.46) in the VTd arm and 1.02 (0.71–1.47) in the D-VTd arm. Median TTP was NR for DARA vs 46.7 mo for OBS (HR 0.49; 95% CI 0.38–0.62; P <0.0001). More pts in the DARA vs OBS arm achieved ≥CR (72.9% vs 60.8%; OR 2.17; 95% CI 1.54–3.07; P <0.0001). MRD negativity (in ≥CR pts at 10-5) was 58.6% with DARA vs 47.1% with OBS (OR 1.80; 95% CI 1.33–2.43; P= 0.0001). Median OS was NR in either arm. Most common (≥2.5%) grade 3/4 adverse events (AEs) with DARA vs OBS were pneumonia (2.5% vs 1.4%), lymphopenia (3.6% vs 1.8%), and hypertension (3.0% vs 1.6%). Serious AEs occurred in 22.7% (DARA) vs 18.9% (OBS) of pts; the most common (≥2.5%) was pneumonia (2.5% vs 1.6%). 13 (3.0%) pts discontinued DARA due to an AE. The rate of infusion-related reactions was 54.5% (DARA-naïve pts) and 2.2% (prior DARA pts); 90% were grade 1/2.Second primary malignancies occurred in 5.5% (DARA) vs 2.7% (OBS) of pts. Conclusions: CASSIOPEIA part 2 demonstrated a clinical benefit of DARA maintenance in TE NDMM pts, with significantly longer PFS for DARA vs OBS. With current follow-up, maintenance PFS benefit appeared only in pts treated with VTd as ind/cons. Pts who received D-VTd ind/cons with or without DARA maintenance achieved similar PFS; longer follow-up is needed for PFS2 and OS. DARA significantly increased deeper response and MRD negativity rates vs OBS, and was well tolerated with no new safety signals. Clinical trial information: NCT02541383.

Atezolizumab in combination with bevacizumab in patients with unresectable locally advanced or metastatic mucosal melanoma: Interim analysis of an open-label phase II trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9511-9511
Author(s):  
Lu Si ◽  
Meiyu Fang ◽  
Yu Chen ◽  
Lili Mao ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Mucosal Melanoma ◽  
Stage I ◽  
Efficacy Evaluation ◽  
Open Label ◽  
Full Analysis ◽  
Ecog Ps

9511 Background: Mucosal melanoma is a rare malignant melanoma in Caucasians but ranks the second most common subtype in the Asian population. It is more often diagnosed at an advanced stage and responds poorly to current PD-1/PD-L1 inhibitors. Here we report the interim analysis results of ML41186, an open-label, multicenter, single-arm phase II study, aiming to evaluate the efficacy and safety of atezolizumab in combination with bevacizumab in patients (pts) with advanced mucosal melanoma. Methods: Eligible pts aged 18 to 75 years with histologically confirmed unresectable locally advanced or metastatic mucosal melanoma had at least one measurable lesion per RECIST version 1.1 at baseline, with an ECOG PS 0 or 1 and adequate hematologic and organ function. ML41186 is a Simon two-stage design study, if 22 pts completed ORR evaluation and more than 3 pts respond in stage I, the study then continue to Stage II. Atezolizumab and bevacizumab were administered at a fixed dose of 1200 mg and 7.5 mg/kg Q3W respectively (on day 1 of each 21-day cycle) until unacceptable toxicity or loss of clinical benefit. The primary endpoint is the objective response rate (ORR). The secondary endpoints include progression-free survival (PFS), duration of objective response (DoR), disease control rate (DCR), and safety. Results: By the cut-off date of 9th September 2020, 35 pts has been enrolled, among whom 22 pts in the stage I analysis set has completed two efficacy evaluation, while 28 pts (full analysis set) has completed at least one efficacy evaluation. In ITT populations (n=35), mean age was 58.9 years with 10 (28%) pts had ECOG PS of 1. LDH level elevated in 9 (25.7%) pts. More than half pts (19, 54.3%) had metastatic mucosal melanoma, of whom 3 (15.8%) pts had more than 3 metastasis sites and 4 (21.1%) pts had liver metastasis. In stage I analysis set (n=22), the best confirmed ORR was 36.4% (95% CI, 17.0%-59.3%). Median progression-free survival was 5.32 months (95% CI, 1.58-not reached), and the best confirmed DCR was 59.1% (95%CI, 36.4%-79.3%). The median confirmed DoR was not reached (95% CI, 2.76-NR). In the full analysis set (n=28), the unconfirmed ORR was 42.9% (95%CI, 24.5%-62.8%). In ITT populations (n=35), 28 pts (80%) experienced at least one adverse event (AE) and 5 pts (14.3%) experienced at least one grade 3-4 AEs. Only one patient experienced AE leading to treatment discontinuation. One patient died of autoimmune lung disease. Conclusions: The combination of atezolizumab plus bevacizumab showed promising benefit and was tolerable in pts with advanced mucosal melanoma. At the time of this interim analysis, the primary endpoint did not cross the futility boundary, thus the study will run into Stage II. Clinical trial information: NCT04091217.

A phase 2 study of pamiparib in the treatment of patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1087-1087
Author(s):  
Tao Sun ◽  
Yanxia Shi ◽  
Jiuwei Cui ◽  
Yongmei Yin ◽  
Quchang Ouyang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brca Mutation ◽  
Objective Response ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer

1087 Background: Breast cancer is the most common cancer among women, with up to 37% of patients (pts) harboring germline BRCA1/2 mutations (g BRCA1/2m) that appear to be sensitive to poly (ADP-ribose) polymerase proteins 1 and 2 (PARP1/2) inhibition. Pamiparib is an orally administered selective PARP1/2 inhibitor that has the potential to cross the blood-brain barrier. This study evaluated the efficacy and safety of pamiparib in pts with locally advanced/metastatic human epidermal growth factor receptor 2-negative (HER2-) breast cancer, with deleterious or suspected deleterious g BRCA1/2m, who received ≤ 2 prior lines of chemotherapy. Methods: In this open-label, phase 2, multi-center study in China (NCT03575065), pts with locally advanced/metastatic HER2- breast cancer with deleterious or suspected deleterious g BRCA1/2m triple negative breast cancer (TNBC cohort) or hormone receptor-positive (HR+)/HER2- breast cancer (HR+ cohort) were enrolled. Pts received pamiparib 60 mg orally twice daily in 28-day cycles. The primary endpoint was objective response rate (ORR; RECIST v1.1) by independent review committee (IRC). Secondary endpoints included duration of response (DOR) and progression free survival (PFS) by IRC, overall survival (OS), safety and tolerability. Results: 88 pts were enrolled (median age 45.5 years), 76 pts (TNBC cohort n = 55; HR+ cohort n = 21) had measurable disease at baseline per IRC. 60 pts (68.2%) received 1 or 2 prior lines of chemotherapy; 42 pts (47.7%) were treated with platinum previously. Median follow-up was 13.77 months (TNBC cohort, 10.87 months; HR+ cohort, 18.45 months). In the TNBC cohort: confirmed ORR was 38.2% (95% CI: 25.4–52.3); median DOR (mDOR) was 6.97 months (95% CI: 3.94–not estimable[NE]); median PFS (mPFS) was 5.49 months (95% CI: 3.65–7.33); median OS (mOS) was 17.08 months (95% CI:13.70–NE). In the HR+ cohort: confirmed ORR was 61.9% (95% CI: 38.4–81.9); mDOR was 7.49 months (95% CI: 5.55–14.75); mPFS was 9.20 months (95% CI: 7.39–11.93); mOS was not reached (NR; 95% CI 18.10–NE). ≥ Grade 3 treatment emergent adverse events (TEAEs) occurred in 54 pts (61.4%); anemia was the most common TEAE, occurring in 77 pts (87.5%). Dose reduction due to TEAEs occurred for 57 pts (64.8%); discontinuations due to TEAEs occurred for 2 pts (2.3%). Conclusions: Pamiparib showed a promising response in pts with locally advanced/metastatic HER2- breast cancer with a g BRCA1/2m. The safety profile of pamiparib was considered acceptable and was generally consistent with therapies in the same class. Clinical trial information: NCT03575065 .[Table: see text]

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): Final results from a phase 2, multicenter, open-label study (DESTINY-CRC01).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3505-3505
Author(s):  
Takayuki Yoshino ◽  
Maria Di Bartolomeo ◽  
Kanwal Pratap Singh Raghav ◽  
Toshiki Masuishi ◽  
Fotios Loupakis ◽  
...  
Keyword(s):  
Safety Profile ◽  
Topoisomerase I ◽  
Objective Response ◽  
Safety Data ◽  
Progression Free Survival ◽  
Drug Discontinuation ◽  
Phase 2 ◽  
Antibody Drug Conjugate ◽  
Primary Analysis ◽  
Open Label

3505 Background: T-DXd is an antibody–drug conjugate of a humanized anti-HER2 antibody bound to a topoisomerase I inhibitor by a cleavable linker. The primary analysis of DESTINY-CRC01 (DS8201-A-J203; NCT03384940), a phase 2, open-label, multicenter study of T-DXd in pts with HER2-expressing mCRC showed promising antitumor activity and a manageable safety profile (cohort A median follow-up [FU], 27.1 weeks; Siena S, ASCO 2020). We present updated longer-term efficacy and safety data. Methods: Pts had centrally confirmed HER2-expressing, RAS wild-type mCRC that progressed after ≥2 prior regimens. 6.4 mg/kg of T-DXd was administered every 3 weeks (Q3W) in 3 cohorts (A: HER2 IHC3+ or IHC2+/ISH+; B: IHC2+/ISH−; C: IHC1+). The primary end point was confirmed objective response rate (ORR) by independent central review in cohort A. Secondary end points were disease control rate (DCR; CR + PR + SD), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: At data cutoff (Dec 28, 2020), 86 pts (A, 53; B, 15; C, 18) received T-DXd. Median age was 58.5 y (range, 27-79), 53.5% were male, and 90.7% had left colon or rectum cancer. Median prior regimens for metastatic disease was 4 (range, 2-11). All pts had prior irinotecan; 30.2% in cohort A had prior anti-HER2 therapy. Median (m) treatment duration (all pts) was 3.0 mo (95% CI, 2.1-4.1; cohort A, 5.1 mo [95% CI, 3.9-7.6]). In cohort A (median FU, 62.4 weeks), confirmed ORR was 45.3% (24/53 pts; 95% CI, 31.6-59.6), DCR was 83.0% (44/53 pts; 95% CI, 70.2-91.9), mDOR was 7.0 mo (95% CI, 5.8-9.5), mPFS was 6.9 mo (95% CI, 4.1-8.7) with 37 (69.8%) PFS events, and mOS was 15.5 mo (95% CI, 8.8-20.8) with 36 (67.9%) OS events. These results are consistent with the primary analysis. Confirmed ORR was 43.8% (7/16 pts; 95% CI, 19.8-70.1) in pts with prior anti-HER2 therapy, 57.5% (23/40 pts; 95% CI, 40.9-73.0) in pts with IHC3+ status, and 7.7% (1/13 pts; 95% CI, 0.2-36.0) in pts with IHC2+/ISH+ status. In cohorts B and C, mPFS was 2.1 mo (95% CI, 1.4-4.1) and 1.4 mo (95% CI, 1.3-2.1); mOS was 7.3 mo (95% CI, 3.0-NE) and 7.7 mo (95% CI, 2.2-13.9), respectively. Treatment-emergent adverse events (TEAEs) of grade (G) ≥3 occurred in 65.1% of pts (56/86); the most common TEAEs were hematologic and gastrointestinal. TEAEs leading to drug discontinuation occurred in 13 pts (15.1%). 8 pts (9.3%) had interstitial lung disease (ILD) adjudicated by an independent committee as related to T-DXd (4 G2; 1 G3; 3 G5). Conclusions: T-DXd at 6.4 mg/kg Q3W showed promising activity and durability with longer-term FU in this pt population. The safety profile was consistent with prior results; ILD continues to be recognized as an important identified risk that requires careful monitoring and intervention as needed. These results support continued exploration of T-DXd in pts with HER2-overexpressing mCRC. Clinical trial information: NCT03384940.

Sign in / Sign up

Export Citation Format

Share Document