Long-term analyses from L-MIND, a phase II study of tafasitamab (MOR208) combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7513-7513
Author(s):  
Johannes Düll ◽  
Kami J. Maddocks ◽  
Eva Gonzalez-Barca ◽  
Wojciech Jurczak ◽  
Anna Marina Liberati ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Open Label ◽  
Efficacy Analysis

7513 Background: L-MIND (NCT02399085) is an ongoing, open-label, Phase II study of tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, plus LEN in ASCT-ineligible patients (pts) with R/R DLBCL. Primary analyses and 2-year efficacy results were previously presented; we report an updated efficacy analysis with ≥35 months follow up (cut-off: October 30, 2020). Methods: Pts were aged ≥18 years with ASCT-ineligible R/R DLBCL, had 1–3 prior systemic therapies (Tx), including ≥1 CD20-targeting regimen, with an ECOG status of 0–2. Pts received 28-day cycles (C) of tafasitamab (12 mg/kg IV), once weekly during C1–3, with a loading dose on Day 4 of C1, then every 2 weeks (Q2W) during C4–12. LEN (25 mg PO) was administered on Days 1–21 of C1–12. After C12, progression-free pts received tafasitamab Q2W until disease progression. The primary endpoint was objective response rate (ORR), assessed by IRC. Secondary endpoints included duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Results: Eighty of 81 enrolled pts received tafasitamab + LEN and were included in the full analysis set (1 prior Tx, n=40; 2+ prior Tx, n=40). At data cut-off, the overall ORR was 57.5% (n=46/80), including complete response (CR) in 40% of pts (n=32/80) and partial response (PR) in 17.5% of pts (n=14/80) (Table). Kaplan-Meier estimates: median DoR=43.9 months (95% CI: 26.1–not reached [NR]), and NR in pts who achieved a CR (95% CI: 43.9–NR); median PFS=11.6 months (95% CI: 6.3–45.7), with median follow-up 33.9 months; median OS=33.5 months (95% CI: 18.3–NR), with median follow-up 42.7 months. There were no unexpected toxicities or new safety signals. Conclusions: Combination Tx with tafasitamab + LEN followed by tafasitamab monotherapy provided durable responses in pts with R/R DLBCL not eligible for ASCT, with a manageable safety profile. These long-term data indicate the potential of tafasitamab + LEN followed by extended tafasitamab monotherapy in achieving prolonged remission and survival benefit in this patient population, especially at first relapse. Clinical trial information: NCT02399085. [Table: see text]

A phase II study of epacadostat and pembrolizumab in patients with advanced sarcoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11049-11049 ◽  
Author(s):  
Ciara Marie Kelly ◽  
Ping Chi ◽  
Mark Andrew Dickson ◽  
Mrinal M. Gounder ◽  
Mary Louise Keohan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Open Label ◽  
Intracellular Enzyme ◽  
Recist 1.1 ◽  
Advanced Sarcoma

11049 Background: Tumors express IDO1, an intracellular enzyme involved in the degradation of tryptophan to kynurenine, in order to evade immunosurveillance. Epacadostat inhibits IDO1 and shifts the tumor microenvironment from an immunosuppressive state to an immune-stimulated state. Pembrolizumab previously demonstrated activity in select sarcoma subtypes. We performed an open-label, single-center, phase II study of epacadostat and pembrolizumab in patients with advanced sarcoma. Methods: Patients received the recommended phase II dose of oral epacadostat (100mg) twice per day and intravenous pembrolizumab (200mg/dose) every 3 weeks. The primary endpoint was best objective response rate (ORR) (complete response and partial response [PR]) at 24 weeks by RECIST 1.1. Secondary endpoints included adverse events (AEs), ORR by irRECIST, progression free survival (PFS) and overall survival (OS). Correlative studies performed on pre/on-treatment biopsy specimens included PD-L1, IDO1, and kynurenine expression and characterization of tumor infiltrating lymphocytes by IHC, whole exome and RNA sequencing. Results: Twenty-nine patients were enrolled [median age 53 years (range, 24-78), 57% male, ECOG PS 0 83%]. Histological subtypes included leiomyosarcoma (17%), UPS (17%), myxofibrosarcoma (7%), liposarcoma (10.5%), EHE (10.5%), angiosarcoma (3%), “other” sarcoma subtype (35%). Patients were refractory to 0 (21%), 1 (38%), 2 (24%) and ≥ 3 (17%) prior lines of therapy. The most common ( > 20% of pts) grade (G)1 or 2 treatment related AEs (TRAEs) observed included fatigue (31%), rash (31%) and ALT elevation (24%). G3 TRAEs included AST elevation (10%), ALT elevation, anemia, hypophosphatemia and increased lipase each occurred in 3% of pts. Three patients discontinued therapy due to G3 immune mediated hepatitis. Among the 29 evaluable patients 1 (3%) confirmed PR (leiomyosarcoma), 13 stable diseases (45%) and 15 progressions (52%) were observed by RECIST 1.1. The median PFS was 8.0 weeks (two-sided 95% CI: 6.9 ~ 26.7) and the PFS rate at 24 weeks was 27.9% (two-sided 95% CI: 15.0% ~ 52.2%). The median OS was not estimable (two-sided 95% CI: 40.9 weeks ~ NE). The OS at 24 weeks was 85.2% (95% CI: 72.8%, 99.7%). Conclusions: Epacadostat in combination with pembrolizumab was generally well tolerated. Limited anti-tumor activity was observed among advanced sarcoma patients. Correlative analyses including determination of adequacy of IDO1 inhibition will be reported. Clinical trial information: NCT03414229.

A Phase II Study of Intravenous Azacitidine Alone in Patients with Myelodysplastic Syndromes NCT00384956.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1451-1451
Author(s):  
Richard Walgren ◽  
Crystal Dao ◽  
Frederieke Kreisel ◽  
Peter Westervelt ◽  
Camille Abboud ◽  
...  
Keyword(s):  
Median Time ◽  
Phase Ii ◽  
De Novo ◽  
Phase Ii Study ◽  
Study Drug ◽  
Complete Response ◽  
Subsequent Treatment ◽  
Open Label ◽  
Erythroid Response

Abstract Rationale: 5-Azacytidine (Aza), a DNA hypomethylating agent, has now been shown in 2 clinical trials involving high-risk MDS patients to provide a survival benefit over supportive/conventional care regimens. While one phase II study used a continuous 7-day IV infusion, Aza was administered subcutaneously (SQ) in most pre-approval studies. However, injection site reactions are not uncommon with SQ dosing, especially in thrombocytopenic patients. Aza given as a short intravenous (IV) infusion is anticipated to be efficacious from pharmacokinetic profiling and is FDA approved, but prospective efficacy data for short IV infusion are lacking. Study aim and design: To determine the efficacy of IV Aza when given as a short infusion, we have undertaken an open-label, single-arm, single-center phase II study of Aza in patients with MDS, either de novo or secondary, defined by FAB classification. Previously treated subjects were ineligible if they had already received Aza or decitabine. Treatment consisted of Aza 75 mg/m2 given as a 20 minute IV infusion once daily on Days 1–5 of a 28-day cycle. Response was evaluated by IWG 2000 criteria. After two cycles at the 75 mg/m2 dose, patients failing to achieve a CR were eligible for an increased dose of 100 mg/m2. After 6 cycles of therapy, patients must have demonstrated at least a hematologic improvement to continue on study. Study endpoints include determination of the complete response (CR) and partial response (PR) rates, and secondary endpoints examined the rates of hematological improvement, time to progression, and cytogenetic response. Results: Accrual began 8/17/06 with a target of 21 subjects. As of 7/31/07, 15 subjects have accrued with a median follow-up of 77 days (range 4 to 246). Subjects consisted of 9 males and 6 females with a median age of 69.6 yr (range 53 to 82). The median time from diagnosis is 213 days (range 0 days to 4 yr). By FAB criteria, subjects consist of 4 RA, 9 RAEB, 1 RAEB-t, and 1 CMML, and subjects are categorized by IPSS risk as 1 Low, 4 Int-1, and 10 Int-2. Two patients had therapy related MDS. The data remain preliminary with subjects having completed a mean of 3 cycles (range 1 to 6). None of the 5 subjects who have completed at least 4 cycles of therapy have achieved a CR. However, 2 (40%) of these subjects achieved a PR. Additionally, 1 (20%) patient had a major erythroid response, while another had a minor erythroid response. Median time to response was 2 months. Ten subjects remain on study, 1 patient withdrew due to progressive disease (in first week of therapy), and 4 deaths have occurred on study (2 due to sepsis, 1 each due to pneumonia and acute MI). No deaths were attributed to study drug. Common adverse events include nausea, emesis, and hematologic toxicities. Grade 2–3 nausea and grade 2–3 emesis each occurred in 5 subjects. Observed grade 3 or 4 hematologic toxicities included: anemia (n=7), thrombocytopenia (n=4), leukopenia (n=3), neutropenia (n=7), and febrile neutropenia (n=1). Hematologic toxicities have resulted in transient treatment delays (< 4 weeks) and dose reduction, but hematologic toxicities have not prevented subsequent treatment on study. Conclusions: Although follow-up is short for assessment of efficacy, this is the first prospective study to report on efficacy and toxicity of short infusional Aza in the treatment of MDS.

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

RAMSETE: A single-arm, multicenter, single-stage phase II trial of RAD001 (everolimus) in advanced and metastatic silent neuro-endocrine tumours in Europe.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4122-4122 ◽  
Author(s):  
Marianne E. Pavel ◽  
Bertram Wiedenmann ◽  
Jaume Capdevila ◽  
Nicholas Reed ◽  
Juan W. Valle ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response ◽  
Mammalian Target Of Rapamycin ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Rate ◽  
Mucosal Inflammation ◽  
Duration Of Treatment ◽  
Open Label ◽  
Best Response

4122 Background: The mammalian target of rapamycin (mTOR) signaling pathway is involved in the pathogenesis of neuroendocrine tumors (NET). Everolimus (RAD001), an oral mTOR inhibitor, has antitumor activity in patients (pts) with advanced NET. In this open-label, multicenter, phase II study (RAMSETE), the safety and efficacy of everolimus monotherapy was evaluated in pts with advanced nonsyndromic, nonpancreatic NET. Methods: Pts with advanced (unresectable or metastatic), progressive, nonsyndromic, nonpancreatic NET received everolimus (10 mg/day) as monotherapy. The primary endpoint was objective response rate (proportion of pts with best overall complete response [CR] or partial response [PR] per RECIST v1.0) by central radiologic review. A secondary endpoint included progression-free survival (PFS). Results: By database soft lock (December 1, 2011), 73 pts from 16 European clinics received everolimus (median duration of treatment: 193 days). Fifty-five (75%) pts discontinued; reasons included disease progression (n=23), adverse events (AEs [n=23]), withdrawal of consent (n=4), death (n=3), and protocol deviation (n=2). In the per protocol population (N=60), 32 (53%) pts received prior antineoplastic therapy. The best response by central review was stable disease in 55%. By local review, 3 (5%) pts had a PR, with SD in 39 (65%) pts. Median PFS by central review was 185 days (95% CI: 158-255). Median PFS by local investigator review was 285 days (95% CI: 231-not estimable). 69 (95%) pts reported treatment-related AEs of any grade, including rash (n=28; 38%), diarrhea (n=20; 27%), mucosal inflammation (n=18; 25%), and decreased appetite (n=17; 23%). Treatment-related grades 3 and 4 AEs and serious AEs were reported by 27 (37%) and 18 (25%) pts, respectively. Conclusions: In this open-label trial of everolimus in pts with advanced, nonsyndromic, extrapancreatic NET, a high rate of disease stabilization was achieved after prior tumor progression with favorable median PFS. This study further supports efficacy of everolimus in types of NET other than those studied in RADIANT-3 (pancreatic NET) and RADIANT-2 (NET associated with carcinoid syndrome).

Long-term follow-up of the GELA LNH 03-7B study: A prospective phase II study of 150 patients over 80 years with diffuse large B-cell lymphoma (DLBCL) treated with RminiCHOP.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8536-8536 ◽  
Author(s):  
Frederic Peyrade ◽  
Olivier Fain ◽  
Bettina Fabiani ◽  
Frederic Bauduer ◽  
Eric Van Den Neste ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
B Cell Lymphoma ◽  
Response To Treatment ◽  
Disease Stage ◽  
Term Survival ◽  
Old Patients ◽  
Prospective Phase

8536 Background: We report the outcome of patients included in the LNH 03-7B prospective phase II study of the GELA group which evaluated the tolerance and efficacy of a reduced dosage chemotherapy regimen (miniCHOP) associated with full dose rituximab in patients aged over 80 years with DLBCL. Methods: Patients were between 80 and 95 years (median 83 years), had disease stage I Bulky to IV and 65% had poor risk lymphoma according to IPI. Perfomance status was 0-2 in all cases. The majority of deaths and grade III/IV toxicity occurred during cycle 1 and 2. Response to treatment and early survival analyses were previously presented with 20 months median follow-up (Lancet oncol 2011;12:460-468). Results: At the time of this analysis, The median follow-up time was 41 months and 75 (50%) patients were alive. The 4-year estimated overall survival (OS) was 49.3% [95% CI: 40.8-57.3%] and the median OS was 38 months. The 4-year estimated PFS, EFS and DFS were 41.4% [95% CI: 33.1-49.5%], 39.4% [95% CI : 31.2-47.5%] and 57.9% [95% CI : 47.3-67.2%] respectively.]. During the additional follow-up, 8 patients relapsed (10% of CR patients) and 17 died. No long term toxicity was recorded. In a multivariate analysis an albumin level >35 g/l remained significantly associated with a longer survival. Conclusions: These results show that very old patients with DLBCL treated with RminiCHOP could express long-term survival and probably be cured. Regarding the DFS and despite the early toxicity, it seems crucial to obtain the best possible response. This long term analysis confirm that in patient aged over 80y with DLBCL and with PS from 0 to 2, RminiCHOP is the treatment cornerstone. Clinical trial information: NCT01087424.

Sintilimab for relapsed/refractory classical Hodgkin’s lymphoma: Extended follow-up on the multicenter, single-arm phase II ORIENT-1 study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7533-7533
Author(s):  
Hang Su ◽  
Yongping Song ◽  
Wenqi Jiang ◽  
Xiuhua Sun ◽  
Wenbin Qian ◽  
...  
Keyword(s):  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Rate ◽  
Hodgkin's Lymphoma ◽  
Primary Analysis ◽  
Hematopoietic Stem

7533 Background: Classical Hodgkin’s lymphoma (cHL) is characterized by chromosome 9p24.1 alterations and PD-1 ligand overexpression. Sintilimab, a programmed death-1 checkpoint inhibitor, has demonstrated efficacy in relapsed/refractory cHL after the primary analysis of the ORIENT-1 study. Here, we report the updated safety and efficacy prolines after extended follow-up. Methods: ORIENT-1 is a multicenter, single-arm, phase II study in China. Classical Hodgkin’s lymphoma patients who had failed ≥2 lines of systemic therapy, including autologous hematopoietic stem cell transplantation (HSCT) were enrolled. Sintilimab, 200 mg IV was given every 3 weeks, until disease progression, death, unacceptable toxicity, or withdrawal from study. The primary endpoint was objective response rate (ORR) assessed by an independent radiological review committee (IRRC) according to 2007 IWG criteria. Results: 96 patients were treated. As of the data cutoff on 16 October, 2018 72.9% of patients were continuing treatment with a median follow-up of 14 months. Median number of treatment cycles was 20 (range: 1 to 26). ORR was 85.4% (82/96, 95%CI: 76.7 to 91.8) based on IRRC review. Twenty-eight patients (29.2%) achieved complete response (CR) by PET scan. At the time of analysis, 59 out of 82 patients who had achieved complete or partial response continued to have an on-going response. The median duration of response (DoR) and progression free survival (PFS) have not been reached. The most common treatment-related adverse event (TRAE) was pyrexia (40.6%, 39/96), 92.3% of which was grade 1 or 2. The most common grade 3 or 4 TRAEs were pyrexia (3.1%) and anemia (3.1%). One death occurred which was not considered treatment related. Conclusions: ORIENT-1 study has the largest cohort of cHL patients in China treated with a PD-1. In addition to a high rate of response, sintilimab also demonstrated durable efficacy and favorable long-term safety profile after extended follow-up. Clinical trial information: NCT03114683.

Phase II Study of Avelumab in Patients With Mismatch Repair Deficient and Mismatch Repair Proficient Recurrent/Persistent Endometrial Cancer

2019 ◽  
Vol 37 (30) ◽  
pp. 2786-2794 ◽  
Author(s):  
Panagiotis A. Konstantinopoulos ◽  
Weixiu Luo ◽  
Joyce F. Liu ◽  
Doga C. Gulhan ◽  
Carolyn Krasner ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Mismatch Repair ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Immune Checkpoint Blockade ◽  
Mmr Proteins

PURPOSE Despite the tissue-agnostic approval of pembrolizumab in mismatch repair deficient (MMRD) solid tumors, important unanswered questions remain about the role of immune checkpoint blockade in mismatch repair–proficient (MMRP) and –deficient endometrial cancer (EC). METHODS This phase II study evaluated the PD-L1 inhibitor avelumab in two cohorts of patients with EC: (1) MMRD/ POLE (polymerase ε) cohort, as defined by immunohistochemical (IHC) loss of expression of one or more mismatch repair (MMR) proteins and/or documented mutation in the exonuclease domain of POLE; and (2) MMRP cohort with normal IHC expression of all MMR proteins. Coprimary end points were objective response (OR) and progression-free survival at 6 months (PFS6). Avelumab 10 mg/kg intravenously was administered every 2 weeks until progression or unacceptable toxicity. RESULTS Thirty-three patients were enrolled. No patient with POLE-mutated tumor was enrolled in the MMRD cohort, and all MMRP tumors were not POLE-mutated. The MMRP cohort was closed at the first stage because of futility: Only one of 16 patients exhibited both OR and PFS6 responses. The MMRD cohort met the predefined primary end point of four ORs after accrual of only 17 patients; of 15 patients who initiated avelumab, four exhibited OR (one complete response, three partial responses; OR rate, 26.7%; 95% CI, 7.8% to 55.1%) and six (including all four ORs) PFS6 responses (PFS6, 40.0%; 95% CI, 16.3% to 66.7%), four of which are ongoing as of data cutoff date. Responses were observed in the absence of PD-L1 expression. IHC captured all cases of MMRD subsequently determined by polymerase chain reaction or genomically via targeted sequencing. CONCLUSION Avelumab exhibited promising activity in MMRD EC regardless of PD-L1 status. IHC for MMR assessment is a useful tool for patient selection. The activity of avelumab in MMRP/non- POLE–mutated ECs was low.

A phase II study of a novel anti-tubulin, E7389, in patients with advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7106-7106
Author(s):  
A. Das ◽  
A. Spira ◽  
N. Iannotti ◽  
M. Savin ◽  
E. Zang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Study Drug ◽  
Progression Free Survival ◽  
Large Cell ◽  
Median Number ◽  
Synthetic Analog ◽  
Open Label ◽  
Best Response

7106 Background: E7389, a synthetic analog of halichondrin B that was isolated from a marine sponge, has broad anti-proliferative activity at nanomolar levels and a unique profile of tubulin interactions. Methods: This is an open-label, single-arm, stratified phase II study of E7389 in patients with measurable, recurrent and/or metastatic NSCLC who progressed during or after platinum-based doublet chemotherapy. E7389 (1.4 mg/m2) was administered as a bolus IV on days 1, 8, and 15 of a 28-day cycle to 72 patients (cohort 1) in stratum I (55 taxane pretreated patients) and stratum II (17 taxane-naive patients) and on Days 1 and 8 of a 21-day cycle (cohort 2), providing an additional 22 patients in stratum I. The primary efficacy endpoint was objective response rate to E7389 monotherapy. Results: As of 9 December 2005, 94 evaluable patients received E7389. Nineteen tumors were classified as squamous cell carcinomas, 39 as adenocarcinomas, and 36 were large cell carcinomas or unclassified. The median number of cycles completed was 3. Fifteen patients completed 6 or more cycles and 75 patients underwent tumor assessments after cycle 2. Major toxicities related to study drug included myelosuppression, nausea, fatigue, dehydration, arthralgias, dyspnea, and peripheral neuropathy. Based on RECIST criteria, 6 partial responses (PR) were observed among 94 evaluable patients (PR rate = 6.4%, 95% CI: 2.8%, 12.8%). For 33 patients the best response was stable disease (SD rate = 35.1%, 95% CI: 25.5%, 45.1%). Disease control rate (PR + SD) was 41.5% (95% CI: 31.4%, 51.7%). For cohort 1, the 12-week progression free survival rate was 57.2%. As of 9 December 2005, median PFS time was 108 days (95% CI = 55, min-max = 1–239+). Cohort 2 is being followed to estimate their 12-week PFS. The correlation of beta tubulin isotype, stathmin, microtubule-associated protein 4 (MAP4) and tau protein mRNA expression with tumor responses is on-going. Conclusions: Based on this data, E7389 has been shown to be safe and effective in the treatment of NSCLC patients. Updated information and results of molecular correlations of responses will be presented. [Table: see text]

A phase II study of everolimus in patients with aggressive RAI refractory (RAIR) thyroid cancer (TC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6023-6023 ◽  
Author(s):  
Jochen H. Lorch ◽  
Naifa Busaidy ◽  
Daniel T Ruan ◽  
Pasi A. Janne ◽  
Sewanti Atul Limaye ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Protein A ◽  
Progression Free Survival ◽  
Complete Response ◽  
Negative Regulator ◽  
High Rate ◽  
Loss Of Function ◽  
Open Label ◽  
Mechanistic Basis

6023 Background: We present results of an open label phase II study of the mTOR inhibitor Everolimus in patients (pts) with RAIR TC. Methods: Pts with metastatic, incurable RAIR TC who had shown radiographic progression within 6 months prior to enrollment received Everolimus 10mg orally once daily. Responses were monitored by CT's every two months. The primary endpoint was progression free survival. Sequential biopsies were obtained in selected pts. Results: Enrollment to the differentiated TC (DTC) cohort finished in Jan 2013 and included 33 pts, among them 11 with Hurthle cell TC. Exploratory cohorts enrolled 10 pts with medullary [MTC] and 5 with anaplastic [ATC] with 2 added openings remaining for ATC. For the DTC cohort, median time on study to date is 10 months (mo) (<1-23+). 31 pts are evaluable at this time. PFS in the DTC cohort by Kaplan-Meier (K-M) analysis is 16.0 mo (95%CI 10-NR). Currently, disease stability for 6 and 12 mo or more was achieved in 18 and 10/31 pts, respectively, 11 pts remain on study. Median OS was not reached but 1 year survival by K-M analysis was 76%. One pt achieved a PR. 3 pts with DTC underwent sequential biopsies which revealed activation of autophagy while markers for apoptosis were not detected. Among 10 MTC pts, one achieved a PR and 9 pts had stable disease for 6 mo or more (6-33+). Among 5 ATC pts, 3 progressed, one has ongoing disease stability for 5 mo. One patient achieved a complete response that lasted for 18 mo and whole exome sequencing revealed somatic loss of function mutation affecting the Tuberous Sclerosis 2 (TSC2) protein, a negative regulator of mTOR activity [TSC2 (Q1178*) and FLCN (R17fs)]. Most common treatment-related adverse events were as anticipated and included fatigue, stomatitis and infections. Grade (gr) 3 events included infection 5, weight loss 3, leukopenia 3, thrombocytopenia 3, fatigue 3, hypophosphatemia 2, stomatitis 2, pneumonitis 1 and thrombosis 1pts. One pt had gr 4 hypercholesterinemia and one pt had gr 4 leukopenia. Conclusions: Everolimus has significant anti-tumor activity in pts with advanced TC. Activation of autophagy could account for high rate of disease stability. Sequencing may identify mechanistic basis and predictive markers for treatment response. Clinical trial information: NCT00936858.

Phase II study of afatinib in recurrent and/or metastatic esophageal squamous cell carcinoma (R/M ESCC) (KCSG HN14-18).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4051-4051
Author(s):  
Min Hee Hong ◽  
Yun-Gyoo Lee ◽  
Hyo Song Kim ◽  
Keon Uk Park ◽  
Hoon-Gu Kim ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Clinical Investigation ◽  
Objective Response ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Open Label ◽  
Platinum Based Chemotherapy

4051 Background: Afatinib, an irreversible pan-ErbB kinase inhibitor showed anti-tumor activity against esophageal cancer in phase I trial. In this multicenter, open-label, single arm phase II study, we aimed to evaluate the activity and safety of afatinib in R/M ESCC. Methods: Patients (pts) who had ECOG PS 0-2 and had progressed on platinum-based chemotherapy for R/M ESCC were enrolled. Pts were treated with afatinib 40mg/day until disease progression, unacceptable toxicity, or patient’s refusal. Primary endpoint was objective response rate (ORR) per RECIST 1.1. The estimated sample size was 49, using a two-stage minimax design to evaluate incremental response rate from 5 to 15%. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety profile. Additionally, we try to identify biomarker to predict efficacy of afatinib with target capture sequencing and gene expression profile as exploratory endpoints. Results: In a total of 49 enrolled pts (median age 60; range 44 -84), ORR and DCR were 14.3 % and 73.3%, respectively. With a median follow-up of 6.6 months, median PFS and OS was 3.4 months (95% CI 2.2-4.6) and 6.6 months (95% CI 5.2-8.0). Median treatment duration and duration of response were 2.8 months (range, 0.4-15.3) and 7.1 months (range, 2.5-13.9), respectively. Dose reduction and interruption occurred in 19 (38.8%) and 15 (30.6 %) pts. Treatment-related adverse events (TRAE) occurred in 33 pts (67.3%) with most common TRAEs being diarrhea (n=22, 44.9%) and acneiform rash (n=12, 24.5%). G3-4 TRAEs were rare, occurring in 7 pts (14.3 %). Conclusions: Afatinib demonstrated modest efficacy with manageable toxicity in platinum-resistant R/M ESCC patients. Given the modest response rate, identification of predictive biomarkers is essential for further clinical investigation of afatinib in R/M ESCC. Those biomarkers are being analyzed and will be presented in the conference (NCT02353936). Clinical trial information: NCT02353936. [Table: see text]

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