A phase II study of oraxol in the treatment of unresectable cutaneous angiosarcoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11517-11517 ◽  
Author(s):  
Vinod Ravi ◽  
Michael Wagner ◽  
Tom Wei-Wu Chen ◽  
Herbert H. F. Loong ◽  
Robert Gary Mennel ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Objective Response ◽  
Tumour Response ◽  
Open Label ◽  
Stage Design ◽  
Once Daily ◽  
Open Label Study ◽  
Prior Therapy ◽  
Low Incidence ◽  
Dose Reductions

11517 Background: Oraxol is a combination of oral paclitaxel and a novel oral P-glycoprotein inhibitor, HM30181A. Cutaneous angiosarcomas are highly aggressive malignant tumors with poor prognosis. Currently there is no FDA-approved treatment. Methods: This is an open label study evaluating the activity, safety and tolerability of Oraxol 205mg/m2 administered orally, once daily, for 3 consecutive days per week. Planned treatment is for 25 weeks. Subjects included in this study had not received prior therapy with a taxane and did not have metastatic disease. Tumour response was evaluated at 6 weekly intervals using RECIST and photography. A Simon two stage design was used. Results: 18 of 24 enrolled patients (pts); male/female 11/7; median age 77 years (range 56-93), were evaluable at time of analysis. Subjects were recruited during an 18 month period, from Aug-2018 to Jan-2020. Best objective response rates were: CR 22% (n = 4), PR 11% (n = 2), SD 67% (n = 12), PD 0%. 42% of pts with SD had durability > 13 weeks (range 13-25). Median PFS was 38 weeks. All pts remain alive at time of reporting. Furthermore, 5 pts (28%) who had inoperable lesions were deemed operable after Oraxol and received surgical resection. Oraxol was generally well tolerated. Most common adverse events (AEs) G>3 were: diarrhea (n = 1), fatigue (n = 3), neutropenia (n = 9), leucopenia (n = 5), lymphopenia (n = 5). Serious AEs were G3 pneumonia in 2 subjects and G4 neutropenia in 2 subjects, one of which was febrile. All events fully resolved. Neuropathy was uncommon: n = 2 (G1 = 1 @ day 10, G2 = 1 @ day 64). Dose reductions were recorded in 7 subjects. 2 subjects discontinued treatment due to AEs; both asymptomatic pneumonitis seen on CT, which recovered after discontinuation. Following the initial positive results, the protocol has been amended to change the maximum recruitment of subjects from 25 to 43. Conclusions: Oraxol provides an orally administered treatment option for angiosarcoma, with a high and durable clinical benefit rate (CR + PR+ long SD). It is generally well tolerated even in an older patient population; particularly with respect to the the low incidence of neuropathy compared to IV paclitaxel. Recruitment is ongoing. Clinical trial information: NCT03544567 . [Table: see text]

A phase II, open-label study of PTK787/ZK222584 in the treatment of metastatic gastrointestinal stromal tumors (GISTs) resistant to imatinib mesylate

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9531-9531 ◽  
Author(s):  
H. Joensuu ◽  
F. De Braud ◽  
P. Coco ◽  
T. De Pas ◽  
C. Spreafico ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Treatment Failure ◽  
Tyrosine Kinases ◽  
Imatinib Treatment ◽  
Open Label ◽  
Cancer Treatments ◽  
Once Daily ◽  
Open Label Study ◽  
Prior Therapy ◽  
Imatinib Resistant

9531 Background: PTK787/ZK222584 (PTK/ZK) is a novel, oral selective inhibitor of certain receptor tyrosine kinases that may be important in the molecular pathogenesis of GIST (KIT, PDGFRs, VEGFR-1 and VEGFR-2). The efficacy and safety of PTK/ZK are not known in the treatment of imatinib resistant GIST. Methods: Pts who had histologically diagnosed, metastatic GIST that had progressed after at least 4 weeks of treatment with imatinib were eligible. Prior therapy with KDR inhibitor therapy was not allowed. PTK/ZK was administered orally 1,250 mg once daily until treatment failure. No concomitant systemic cancer treatments were allowed. Treatment response was monitored at 4 to 8 wk intervals and evaluated using the RECIST criteria. Adverse events (AE) were scored using the NCI/NIH Common Toxicity Criteria v. 2.0. A total of 15 pts were planned to be accrued as a 2-stage procedure. The highest prior imatinib dose: 400 mg, n=1; 600 mg, n=2; 800 mg, n=11; 1,000 mg, n=1. Prior response to imatinib: PR, n=8; SD, n=5; PD, n=1; unknown, n=1. Results: All 15 pts (M 12, F 3) enrolled were eligible. Two (13%) pts achieved PR, 8 (53%) had SD for 3 months or longer, and 5 progressed. The clinical benefit rate (PR+SD) was 67% (95% CI, 38% to 86%). The duration of the 2 PRs was 95 + and 225+ days and 8 SDs from 93+ to 346+ days. All PRs and SDs are ongoing to date. The median time to treatment failure (TTTF) has not been reached. PTK/ZK was well tolerated. The most frequently recorded AEs were dizziness (n=6), nausea/vomiting (n=6), abdominal pain/abdominal pain upper (n=4) and asthenia (n=4). All recorded AEs were either of grade 1 or 2 except for 2 events (grade 4 hypercalcemia, n=1; grade 4 pain, n=1). Conclusions: PTK787/ZK222584 showed signs of activity in this series of GIST patients who progressed during imatinib treatment. The dose of 1,250 mg o.d. is generally well tolerated. [Table: see text]

scholarly journals Fosamprenavir plus Ritonavir Increases Plasma Ketoconazole and Ritonavir Exposure, while Amprenavir Exposure Remains Unchanged

2007 ◽  
Vol 51 (8) ◽  
pp. 2982-2984 ◽  
Author(s):  
Mary B. Wire ◽  
Charles H. Ballow ◽  
Julie Borland ◽  
Mark J. Shelton ◽  
Yu Lou ◽  
...  
Keyword(s):  
Steady State ◽  
Healthy Subjects ◽  
Open Label ◽  
Time Curve ◽  
Once Daily ◽  
Open Label Study ◽  
Label Study ◽  
Concentration Time

ABSTRACT Plasma ketoconazole (KETO), amprenavir (APV), and ritonavir (RTV) pharmacokinetics were evaluated in 15 healthy subjects after being treated with KETO at 200 mg once daily (QD), fosamprenavir (FPV)/RTV at 700/100 mg twice daily (BID), and then KETO at 200 mg QD plus FPV/RTV at 700/100 mg BID in this open-label study. The KETO area under the concentration-time curve at steady state was increased 2.69-fold with FPV/RTV. APV exposure was unchanged, and RTV exposure was slightly increased.

PULSE: A randomized phase II open label study of panitumumab rechallenge versus standard therapy after progression on anti-EGFR therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS143-TPS143
Author(s):  
John H. Strickler ◽  
Fang-Shu Ou ◽  
Tanios S. Bekaii-Saab ◽  
Christine Megerdichian Parseghian ◽  
Andrea Cercek ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Benefit ◽  
Objective Response ◽  
Progression Free Survival ◽  
Wild Type ◽  
Open Label ◽  
Genomic Alterations ◽  
Open Label Study ◽  
Label Study ◽  
Randomized Phase Ii

TPS143 Background: Patients with KRAS and NRAS ( RAS) wild-type mCRC benefit from the epidermal growth factor receptor (EGFR) monoclonal antibodies (Abs) panitumumab and cetuximab, but nearly all patients experience resistance. Blood-based profiling of cell free DNA (cfDNA) can identify genomic alterations that drive acquired EGFR Ab resistance. After discontinuation of anti-EGFR Abs, acquired genomic alterations decay over time to undetectable levels. Some studies have suggested clinical benefit from EGFR Ab rechallenge, but there is limited evidence that EGFR Ab rechallenge improves survival compared to standard of care (SOC) therapies. We hypothesize that cfDNA profiling will identify patients appropriate for panitumumab rechallenge, and that these molecularly selected patients will have improved survival compared to current SOC therapies. Methods: This is a randomized phase II, open label study designed to compare the overall survival (OS) of panitumumab rechallenge versus SOC (investigator choice TAS-102 or regorafenib). Secondary objectives include comparisons of progression free survival, objective response rate, clinical benefit rate, and quality of life as measured by the linear analogue self-assessment (LASA) questionnaire. Eligible patients have radiographically measurable KRAS, NRAS, and BRAF codon 600 wild-type mCRC based on tumor tissue testing, and must have experienced progression or intolerance to treatment with a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF Ab, and an anti-PD-1 Ab if the tumor has mismatch repair deficiency or is MSI-H. Progression after at least 4 months treatment with an anti-EGFR Ab is required. All patients must be enrolled in the COLOMATE cfDNA screening protocol (NCT03765736) and meet molecular eligibility based on Guardant360 cfDNA profiling (absence of amplification of ERBB2, KRAS, NRAS, and MET; absence of mutations of BRAF, EGFR, ERBB2, KRAS, NRAS, and MET [mutant allele frequency > 0.5%]). Greater than 90 days must have elapsed between the most recent treatment with an anti-EGFR Ab and cfDNA profiling. Dosing for all study drugs is according to clinical SOC. 120 patients will be randomized 1:1 to panitumumab rechallenge or SOC. With 83 OS events, this study will have 80% power to detect an improvement in median OS from 6.5 to 10 months (HR=0.65; 1-sided α= 0.15). This study began enrollment in 6/2020. Recruitment is ongoing at 16 sites in the Academic and Community Cancer Research United (ACCRU) network (ACCRU-GI-1623). Clinical trial information: NCT03992456.

scholarly journals Pharmacokinetics, Safety, and Clinical Outcomes of Omadacycline in Women with Cystitis: Results from a Phase 1b Study

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
J. Scott Overcash ◽  
Pouru Bhiwandi ◽  
Lynne Garrity-Ryan ◽  
Judith Steenbergen ◽  
Stephen Bai ◽  
...  
Keyword(s):  
Clinical Success ◽  
Open Label ◽  
Once Daily ◽  
Open Label Study ◽  
End Of Treatment ◽  
Urine Concentrations ◽  
Phase 1B ◽  
Blood And Urine Samples ◽  
Group 3 ◽  
Group 2

ABSTRACT Omadacycline, an aminomethylcycline antibiotic, is approved as once-daily intravenous (i.v.) and oral (p.o.) monotherapy for acute bacterial skin and skin structure infections and for community-acquired bacterial pneumonia, and it is under development for treatment of urinary tract infection (UTI). This is a phase 1b, randomized, open-label study of omadacycline in women with cystitis (defined as UTI symptoms and a positive urine leukocyte esterase test). Patients received omadacycline for 5 days (group 1: 200 mg intravenously on day 1, then 300 mg orally every 24 h [q24h]; group 2: 300 mg orally every 12 h [q12h] on day 1, then 300 mg orally q24h; group 3: 450 mg orally q12h on day 1, then 450 mg orally q24h). Blood and urine samples were collected over 5 days. Investigator-assessed clinical response was determined at end of treatment (EOT; day 6) and posttreatment evaluation (PTE; 5 to 9 days after last dosing). A total of 31 women were treated. At steady state (day 5), the range of mean omadacycline urine concentrations over 24 h across the groups was 17.94 to 48.12 μg/ml. The most common treatment-emergent adverse events were gastrointestinal (including nausea [60% to 73%] and vomiting [20% to 40%]) and were generally mild and transient. Investigator-determined clinical success was observed in 94% and 84% of patients at EOT and PTE, respectively, with similar results across groups. A favorable microbiological response at PTE was observed in 78% of patients who had a baseline pathogen. Omadacycline is partially excreted in urine and appears to be safe and well tolerated. These preliminary results indicate that omadacycline warrants further evaluation in larger controlled UTI studies.

PROPEL: Results of the pivotal, multicenter, phase II study of pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8561-8561
Author(s):  
O. O'Connor ◽  
B. Pro ◽  
L. Pinter-Brown ◽  
L. Popplewell ◽  
N. Bartlett ◽  
...  
Keyword(s):  
International Workshop ◽  
Performance Status ◽  
Objective Response ◽  
Response To Therapy ◽  
Mucosal Inflammation ◽  
Cell Transplant ◽  
Open Label ◽  
Ecog Performance Status ◽  
Pivotal Phase ◽  
Prior Therapy

8561 Background: Pralatrexate is a novel targeted antifolate designed to accumulate preferentially in cancer cells. PROPEL, a pivotal phase 2, non-randomized, open-label, international study, is the largest prospective study in patients (pts) with relapsed or refractory PTCL. Methods: Pts received 30 mg/m2 of pralatrexate intravenously weekly for 6 of 7 weeks, supplemented with B12 and folic acid. Primary endpoint = objective response rate (ORR); secondary endpoints = response duration, progression-free survival, and overall survival. Eligibility criteria: histologically confirmed PTCL, disease progression after ≥ 1 prior treatment, and ECOG performance status ≤ 2. Pathology was confirmed by independent central review, response to therapy was assessed by independent central review using International Workshop Criteria (IWC). Results: 115 pts were enrolled, 109 were evaluable for efficacy. 111 treated pts included 76 males (68%) and 35 females (32%). Pts had failed a median of 3 prior regimens and thus were heavily pre-treated. 78 pts (70%) failed CHOP, 18 (16%) had previous autologous stem cell transplant. 25% of pts never responded to any prior therapy; 53% did not respond to last prior therapy. The majority (59 pts, 53%) had PTCL not-otherwise specified. The ORR by central review was 27% (n = 29). 11 pts (10% overall, 38% of responders) had a complete response (CR), 18 pts (17%) had a partial response (PR), and 23 (21%) had stable disease. ORR by investigators assessment was 39% (n = 42). The median duration of response cannot be accurately estimated at this time, though responses of > 1 year have been observed. 69% of responses were after just 1 cycle. 5 responding pts went on to transplant. The most frequent Grade (Gr) 3–4 adverse events were mucosal inflammation (Gr 3 = 17%, Gr 4 = 4%) and thrombocytopenia (Gr 3 = 14%, Gr 4 = 19%). Conclusions: The results of PROPEL show that pralatrexate exhibits substantial activity in pts with relapsed or refractory PTCL, as assessed by a rigorous central review, with durable CRs /PRs, irrespective of the amount of prior therapy. [Table: see text]

Phase II randomized, open-label study of YM155 (sepantronium bromide) plus docetaxel versus docetaxel alone as first-line treatment for HER2 negative metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 548-548
Author(s):  
Michael R. Clemens ◽  
Anne Therese Keating ◽  
Oleg Gladkov ◽  
Fei Jie ◽  
Joyce Steinberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Randomized Study ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Open Label ◽  
Eligibility Criteria ◽  
Prior Therapy

548 Background: YM155 (YM) is a small molecule survivin suppressant. In a phase I/II study of YM plus docetaxel (D) in solid tumors evidence of anti-tumor activity was observed in women with human epidermal growth factor 2 non-overexpressing (HER2 negative) metastatic breast cancer (mBC). Methods: This was a randomized study of YM plus D versus D as 1st line treatment in subjects with HER2 negative mBC. Eligibility criteria were: ECOG < 1, no prior chemotherapy for mBC, and at least one measurable lesion. Primary endpoint was progression free survival (PFS); secondary endpoints were: objective response rate (ORR), overall survival (OS), duration of response (DOR), clinical benefit rate (CBR), time to response (TTR) and safety. YM was administered at 5 mg/m2/day as a 168 hr continuous infusion followed by 14 Day (d) observation and D was administered at 75 mg/m2over 1 hr on d1 every 21d. In the control arm, D was dosed per investigator choice q 21d. Results: 101 subjects were randomized (50 YM + D; 51 D). Median (m) age 55 (range: 25 – 79), 25% had triple negative disease, > 60% had bone and lymph mets, 86% had prior therapy for BC. mPFS (days) was 251 (95%CI: 176 – 333) YM + D vs 252 (95%CI: 202-433) D (p=0.34). ORR, CBR and TTR (YM+D; D): 26% vs. 25.5%; 82% vs. 84.3% and 45 vs 59 d. OS data are immature but showed no difference (p=0.911). Adverse events [AEs (> 25%)] [YM + D% vs D %]: neutropenia 83 vs 84, alopecia 62.5 vs 53, fatigue 50 vs 41.2, nausea 35.4 vs 41.2, leucopenia 27 vs 33 and dyspnoea 33 vs 14. Common (>10%) serious AEs [YM + D% vs D%]: febrile neutropenia 21 vs 8 and neutropenia 10 vs 8. Conclusions: Preclinical and clinical evidence suggested the combination of YM + D may offer additional benefit to D alone in subjects with mBC. This study showed no difference in efficacy, but the combination appeared to be well tolerated. Clinical trial information: NCT01038804.

Phase II study of afatinib, an irreversible ErbB family blocker, in demographically and genotypically defined non-small cell lung cancer (NSCLC) patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8063-8063 ◽  
Author(s):  
Jacques De Greve ◽  
Teresa Moran ◽  
Marie-Pascale Graas ◽  
Daniella Galdermans ◽  
Peter Vuylsteke ◽  
...  
Keyword(s):  
Objective Response ◽  
Open Label ◽  
Erbb Family ◽  
Prior Therapy ◽  
Erbb Family Blocker ◽  
Open Label Trial ◽  
Never Smokers ◽  
Grade 3 ◽  
Nsclc Patients ◽  
Egfr Tkis

8063 Background: EGFR mutation+ (M+) NSCLC pts have an improved response to EGFR TKIs vs non-M+ pts. Data on EGFR FISH+ (gene amplified) and HER2 M+ pts are, however, limited. Afatinib is an irreversible ErbB Family Blocker with efficacy in Ph II/III trials in EGFR M+ NSCLC. This exploratory, open-label trial assessed afatinib in 3 genotypically and demographically defined NSCLC groups. Methods: Never/ex-smokers with stage IIIB/IV lung adenocarcinoma with EGFR M+ tumors who had failed prior EGFR TKIs, HER2 M+ tumors independent of prior therapy, or EGFR FISH+ tumors who received ≤3 prior chemotherapies were enrolled. Afatinib 50 mg qd was administered until disease progression or intolerable adverse events. Tumor assessments (RECIST 1.0) were performed every 8 wks. Pts who progressed on afatinib but experienced clinical benefit could continue treatment with afatinib 40 mg qd + paclitaxel 80 mg/m² qw on days 1, 8 and 15 every 28-day cycle. Primary endpoint: Confirmed objective response. Results: 41 pts were treated: 63% female; median age 63 yrs; 68% never smokers; 32% ex-smokers. 33 pts received afatinib monotherapy only; 8 pts received afatinib followed by afatinib/paclitaxel combination therapy. 78% (n=32) of pts were EGFR M+, 5% (n=2) were EGFR FISH+ and 17% (n=7) were HER2 M+. For afatinib monotherapy, 1 confirmed partial response (PR) was observed (EGFR FISH+), stable disease (SD) was seen in 5/7 HER2 M+, 2/2 EGFR FISH+ and 17/32 EGFR M+ pts, and overall disease control (DC) rate was 59% (n=24); mean duration of DC was 26 wks.Median PFS was 16 wks (17 wks in HER2 M+ pts). Of 8 afatinib/paclitaxel-treated pts, 1 had a confirmed PR and 2 had SD; median PFS was 7 wks. Most frequently reported drug-related AEs in afatinib monotherapy pts were diarrhea (n=39; grade ≥3 n=13), rash/acne (n=33; grade ≥3 n=4) and stomatitis (n=19; grade ≥3 n=2). In the combination arm these were diarrhea (n=4; grade ≥3 n=1) and nausea (n=3; grade ≥3 n=0). Conclusions: Efficacy of afatinib in EGFR M+ NSCLC pts has been established in previous trials. Novel activity of afatinib in HER2 M+ and EGFR FISH+ NSCLC pts has been demonstrated here, with a manageable safety profile of afatinib in the overall population. Clinical trial information: NCT00730925.

Expanded analyses of napoli-1: Phase 3 study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 234-234 ◽  
Author(s):  
Li-Tzong Chen ◽  
Daniel D. Von Hoff ◽  
Chung-Pin Li ◽  
Andrea Wang-Gillam ◽  
Gyorgy Bodoky ◽  
...  
Keyword(s):  
Sensitivity Analyses ◽  
Open Label ◽  
Phase 3 ◽  
Open Label Study ◽  
Prior Therapy ◽  
Previously Treated ◽  
Grade 3 ◽  
Intent To Treat ◽  
To Receive ◽  
Clinical Trial Information

234 Background: MM-398 is a nanoliposomal encapsulation of irinotecan. OS in the ITT population was significantly longer with MM-398+5FU/LV over 5FU/LV alone, and the most frequent grade 3+ AEs included neutropenia, fatigue, and GI effects (diarrhea and vomiting). Expanded, pre-specified analyses of the Phase 3 study are presented. Methods: Patients (n=417) with mPAC previously treated with gemcitabine-based therapy, were randomized 1:1:1 in an open-label study to receive: (A) MM-398 (120 mg/m2 IV over 90 min) q3w; (B) 5FU (2,000 mg/m2 over 24 h) plus racemic leucovorin (LV) (200 mg/m2 over 30 min) x 4w followed by 2w rest; or (C) combination of MM-398 (80 mg/m2 IV over 90 min) prior to 5FU (2,400 mg/m2 over 46 h) and racemic LV (400 mg/m2 over 30 min) q2w. The primary endpoint was OS. The Intent To Treat (ITT) population included all randomized patients; the Per Protocol (PP) population included patients who received at least 80% of the target dose in the first 6 weeks and did not violate any inclusion/exclusion criteria. Results: Analysis of the PP populations confirmed the favorable OS, which was also reflected by the PFS, ORR and CA19-9 levels, of the combination MM-398+5FU/LV arm over the control 5FU/LV arm. The MM-398 monotherapy arm did not show a statistically significant improvement in OS compared with the control arm. Analysis of subgroups, based on pretreatment characteristics including stage at diagnosis, time since initial histological diagnosis, prior lines of therapy, time since last prior therapy, and CA19-9 levels, consistently favored OS for the MM-398+5FU/LV arm over the 5FU/LV arm. Conclusions: Expanded analysis of the PP population and sensitivity analyses support the favorability of MM-398+5FU/LV over 5FU/LV, with a manageable safety profile. Clinical trial information: NCT01494506. [Table: see text]

ELOQUENT-1: A phase III, randomized, open-label trial of lenalidomide/dexamethasone with or without elotuzumab in subjects with previously untreated multiple myeloma (CA204-006).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS8113-TPS8113 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Thierry Facon ◽  
Paul Gerard Guy Richardson ◽  
Robert Z. Orlowski ◽  
Jesùs F. San-Miguel ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Response Duration ◽  
Surface Glycoprotein ◽  
Phase Iii ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Open Label ◽  
Cell Surface Glycoprotein ◽  
Prior Therapy

TPS8113 Background: Elotuzumab (Elo) is a humanized monoclonal IgG1 antibody targeting the cell surface glycoprotein CS1, which is highly expressed on >95% of MM cells. In a MM xenograft mouse model, the combination of Elo + lenalidomide (Len) significantly reduced tumor volume in a synergistic manner compared with either agent alone. In a phase 2 study (N=73) of Elo (10 or 20 mg/kg) in combination with Len and low-dose-dexamethasone (Dex) in pts with RR MM, the 10 mg/kg dose group (n=36) demonstrated objective response rates (ORR) of 92% in all pts, and 100% in pts who had received only 1 prior therapy (n=16). The higher response rate in pts with fewer prior lines of therapy provides a rationale for investigating this combination earlier in the disease course. This randomized, open-label, phase 3 trial will determine if the addition of Elo to Len/Dex improves progression-free survival (PFS) in pts with newly diagnosed, untreated MM. Methods: Pts (N=750) with newly diagnosed symptomatic MM ineligible for stem cell transplant will be randomized in a 1:1 ratio to receive 28-day cycles of Len 25 mg PO (days1-21) and Dex 40 mg PO (days 1, 8, 15 and 22) with or without Elo. Elo dose and schedule is 10 mg/kg IV on days 1, 8, 15, 22 in the first 2 cycles and on days 1 and 15 of cycles 3-18 followed by 20 mg/kg on day 1 of cycle 19 onward. Dex 8 mg IV + 28 mg PO is used during the weeks with Elo. Treatment will continue until disease progression, death, or withdrawal of consent. Pts will be followed up for response every 4 weeks until progressive disease and for survival every 16 weeks. The primary endpoint is PFS (90% power for a hazard ratio [experimental to control arm] of 0.74) and the secondary endpoints are ORR and overall survival. Exploratory endpoints are safety, time to response, duration of response, time to subsequent therapy, health-related quality of life, and pharmacokinetics and immunogenicity of Elo. Potential biomarkers will also be assessed. As of January 1, 2012, 13 pts were enrolled and 9 pts were treated. NCT01335399.

Envafolimab (KN035) in advanced tumors with mismatch-repair deficiency.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3021-3021
Author(s):  
Lin Shen ◽  
Jian Li ◽  
Yanhong Deng ◽  
Weijie Zhang ◽  
Aiping Zhou ◽  
...  
Keyword(s):  
Adverse Events ◽  
Mismatch Repair ◽  
Objective Response Rate ◽  
Interim Analysis ◽  
Response Rate ◽  
Objective Response ◽  
Open Label ◽  
Prior Therapy ◽  
Previously Treated

3021 Background: KN035 is a novel fusion protein of humanized anti-PD-L1 single domain antibody and human IgG1 Fc formulated for subcutaneous injection. This open-label phase II study evaluated the safety and antitumor activity of KN035 in patients with advanced microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) cancer. Methods: The study included patients aged ≥18 years with previously treated MSI-H/dMMR colorectal cancer (CRC) or other advanced solid tumors. MSI-H/dMMR status was assessed centrally for CRC and gastric cancer (GC) and locally for other tumors. KN035 was administered at 150 mg once weekly until progression, unacceptable toxicity, or withdrawal. Tumor assessments were every 8 weeks. The primary endpoint was the objective response rate per RECIST v1.1 by independent radiology review. The primary efficacy population (PEP) included patients with CRC who failed fluoropyrimidine (F), oxaliplatin (O), and irinotecan (I) plus those with advanced GC who had failed at least one prior systemic treatment. This was a planned interim analysis performed after the first 50 patients in the PEP had at least two on-study tumor assessments (PEPi). Results: As of December 17, 2019, 103 patients with MSI-H/dMMR advanced cancers were enrolled at 25 centers in China. The PEPi included 39 patients with CRC and 11 with GC, with a median follow-up of 7.5 months. The overall population included 65 patients with CRC (24 had prior therapy with F and O or I), 18 with GC, and 20 with other tumors, with a median follow-up of 6.7 months. The confirmed objective response rate was 30% (95% CI: 17.9%, 44.6%) in the PEPi, 54.2% (95% CI: 32.8%, 74.4%) in the CRC patients who had prior therapy with F and O or I, and 34.0% (95% CI: 24.9%, 44.0%) in the overall population. Of patients who had an objective response at the interim analysis, 80% of those in the PEPi, 84.6% of CRC patients who had prior therapy with F and O or I, and 85.7% of those in the overall population were still responding at the time of data cutoff. Median progression-free survival was 6.6 months in both the PEPi and the overall population. Median overall survival was not reached in either population. Fourteen (13.6%) patients had grade 3–4 treatment-related adverse events. No grade 5 treatment-related adverse events, pneumonitis, or colitis were reported. Local injection-site reactions, all grade 1 or 2, were reported in nine patients. Conclusions: Envafolimab demonstrated durable anti-tumor activity with a manageable safety profile in patients with previously treated advanced MSI-H/dMMR cancer. Clinical trial information: NCT03667170 .

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