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

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

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

Interim safety and clinical activity in patients (pts) with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma from a multicohort phase 1 study of ramucirumab (R) plus pembrolizumab (P).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 102-102 ◽  
Author(s):  
Ian Chau ◽  
Johanna C. Bendell ◽  
Emiliano Calvo ◽  
Rafael Santana-Davila ◽  
Jordi Rodon Ahnert ◽  
...  
Keyword(s):  
Phase 1 ◽  
Gastroesophageal Junction ◽  
Maculopapular Rash ◽  
Pneumocystis Pneumonia ◽  
Primary Objective ◽  
Clinical Activity ◽  
Duration Of Treatment ◽  
Dosing Regimens ◽  
Grade 3 ◽  
Ecog Ps

102 Background: Angiogenesis and immunosuppression are hallmarks of tumor growth. This is the first study to combine R (anti-VEGFR2) with P (anti-PD-1) to simultaneously target both processes in the tumor microenvironment. Methods: This ongoing, multi-cohort, phase 1a/b trial (NCT02443324) enrolled pts with confirmed G/GEJ adenocarcinoma with prior progression on systemic therapy, measurable disease, ECOG PS 0-1, and baseline tumor tissue. PD-L1 was classified as positive (≥1%) or negative using the DAKO PD-L1 22C3 IHC pharmDx assay. Two dosing regimens were evaluated, Cohort A (R 8 mg/kg on Days 1&8) and Cohort B (R 10 mg/kg on Day 1), given with P 200 mg on Day 1 q3W. The primary objective was to assess safety and tolerability of adding R to P; preliminary efficacy will be examined. Results: As of 23-Jun-2016, 40 G/GEJ pts have been enrolled (Cohort A: n=23; Cohort B: n=17). First pt treated in Cohorts A and B were on 29-Feb-2016 and 26-Oct-2015, respectively. The median age was 59 y, 75% were male, 65% had ECOG PS of 1, 48% were PD-L1 positive, and 70% received study treatment as third or subsequent regimen. Median duration of treatment was 2.1 mo and 4.1 mo for Cohort A and B, respectively. All grades treatment-related AEs (TRAE) occurred in 31 (78%) pts and similar between cohorts; TRAEs in ≥10% of pts were fatigue (30%), infusion related reaction (12.5%), decreased appetite (12.5%), pruritus (10%), maculopapular rash (10%), and hypertension (10%). Ten (25%) pts had grade 3-4 TRAEs, most commonly colitis (7.5%) and hypertension (7.5%). One treatment-related death occurred (pneumocystis pneumonia and pulmonary sepsis). Preliminary efficacy data showed 3 of 40 (7.5%) pts (PD-L1 negative, n=1; PD-L1 positive, n=2) have responded (1 confirmed and 2 unconfirmed PR) to treatment with a 45% disease control rate. Median PFS was 2.10 mo (95% CI, 1.18 to 4.04) and 2.60 mo (1.38, NR) for Cohorts A and B, respectively. Fifteen (37.5%) pts, including all responders, remain on treatment. Conclusions: R+P generated no new safety signals and demonstrated antitumor activity in pts with previously treated advanced G/GEJ adenocarcinoma. Clinical trial information: NCT02443324.

Ramucirumab (R) plus pembrolizumab (P) in treatment naive and previously treated advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: A multi-disease phase I study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4046-4046 ◽  
Author(s):  
Ian Chau ◽  
Johanna C. Bendell ◽  
Emiliano Calvo ◽  
Rafael Santana-Davila ◽  
Hendrik-Tobias Arkenau ◽  
...  
Keyword(s):  
Median Duration ◽  
Gastroesophageal Junction ◽  
Survival Rates ◽  
Kidney Injury ◽  
Primary Objective ◽  
Treatment Naïve ◽  
Previously Treated ◽  
Grade 3 ◽  
Ecog Ps ◽  
Clinical Trial Information

4046 Background: Angiogenesis and immunosuppression are hallmarks of tumor growth. This is the first study to combine R (anti-VEGFR2) with P (anti-PD-1) to simultaneously target both processes in the tumor microenvironment. Methods: Ongoing, multi-cohort, phase 1a/b trial enrolled pts with G/GEJ adenocarcinoma, measurable disease, ECOG PS 0-1, previously treated (Cohorts A and B) or untreated (Cohort A2) for advanced disease. PD-L1 was positive (tumor proportion score [TPS] ≥1%) or negative (TPS < 1%) using the DAKO PD-L1 22C3 IHC pharmDx assay. R was administered at 8 mg/kg on Days 1&8 (Cohorts A and A2) or 10 mg/kg on Day 1 (Cohort B) with P 200 mg on Day 1 q3W. Primary objective- assess safety and tolerability of R+P; preliminary efficacy will be examined. Results: As of 21-Nov-2016, 41 previously treated G/GEJ pts were enrolled. Median age was 58 y, 76% male, 66% had ECOG PS of 1, 46% were PD-L1+, and 59% received study treatment as third or subsequent line. Median duration on therapy was 2.8 mo and 4.1 mo for A and B, respectively. Overall, 33 (80%) pts experienced a treatment-related AE (TRAE) and similar between cohorts A and B. Ten (24%) pts experienced grade 3-4 TRAEs, most commonly colitis (7%) and hypertension (7%). One treatment-related death occurred (pneumonitis and pulmonary sepsis). Responses occurred in 3 (7%) pts with 46% disease control rate (DCR). Progression-free and overall survival rates at 6 mo were 22.4 % (95% CI, 9.8-38.0) and 51.2% (95% CI, 33.9-66.1) respectively. Nine (22%) pts remain on treatment. Eighteen of 25 planned treatment naïve G/GEJ pts were enrolled. Median age was 70 yr, 83% male, 56% had ECOG PS of 0, and PD-L1 status is pending. Median duration on therapy was 2.1 mo. Twelve (67%) pts experienced a TRAE. Grade 3 TRAEs occurred in 5 (28%) pts (hypertension [n = 3], diarrhea, and acute kidney injury). No grade 4-5 events occurred. Preliminary efficacy data showed 3 (17%) pts responded with 50% DCR. Median PFS is immature and 89% of pts remain on treatment. Conclusions: R+P generated no new safety signals and demonstrated encouraging antitumor activity in treatment naïve and previously treatedadvanced G/GEJ adenocarcinoma. Clinical trial information: NCT02443324.

Ramucirumab (Ram) and durvalumab (Durva) treatment of metastatic non-small cell lung cancer (NSCLC), gastric/gastroesophageal junction (G/GEJ) adenocarcinoma, and hepatocellular carcinoma (HCC) following progression on systemic treatment(s).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2528-2528 ◽  
Author(s):  
Yung-Jue Bang ◽  
Talia Golan ◽  
Chia-Chi Lin ◽  
Laetitia Dahan ◽  
Siqing Fu ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Primary Objective ◽  
Bleeding Events ◽  
Venous Thromboembolic Events ◽  
Common Grade ◽  
Venous Thromboembolic ◽  
Previously Treated ◽  
Grade 3 ◽  
Ecog Ps ◽  
Tumor Biopsies

2528 Background: A Phase 1b study (NCT02572687) was conducted to examine the combined effects of Ram (anti VEGFR2) and Durva (anti PD-L1). Methods: Patients (pts) with previously-treated, advanced NSCLC (Cohort [CH] A), G/GEJ adenocarcinoma (CH B), HCC (CH C), ECOG PS 0-1, and no prior Ram or IO therapy, received Ram (10 mg/kg) + Durva (1125 mg) Q3W (CH A) or Ram (8 mg/kg) + Durva (750 mg) Q2W (CH B, C). Primary objective was to assess safety; efficacy was also examined. PD-L1 expression of tumor cells (TC) +/- immune cells (IC) in pretreatment tumor biopsies were assessed using SP263 immunohistochemistry. “High” PD-L1 is ≥25% TC for NSCLC and ≥25% TC or IC for G/GEJ, HCC. Results: CH A, B and C enrolled pts with ECOG PS 1 (%) of 43, 66, 68; and average of 2, 2, 1 prior regimens, respectively. The most common grade 3/4 treatment-emergent adverse events (AE) are hypertension (HTN) (14.3, 17.2, 17.9%), anemia (3.6, 24.1, 21.4%), and fatigue (10.7, 10.3, 10.7%). Grade 3/4 AEs of special interest ( > 5% total pts) for Ram: HTN, bleeding events (3.6, 10.3, 10.7%), Venous thromboembolic events (0, 10.3, 7.1%); for Durva: increase in lipase (10.7, 3.4, 10.6%) and AST (3.6, 3.4, 17.9 %). Data from CH B,C suggest a trend toward increased efficacy in pts with high PD-L1 expressing tumors. Conclusions: Ram + Durva generated no unexpected toxicities and demonstrated antitumor activity. Results in pts with high PD-L1 HCC and G/GEJ cancer warrant further evaluation. Clinical trial information: NCT02572687. [Table: see text]

The combination of venetoclax, lenalidomide, and rituximab in patients with newly diagnosed mantle cell lymphoma induces high response rates and MRD undetectability.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7505-7505
Author(s):  
Tycel Jovelle Phillips ◽  
Alexey Valeryevich Danilov ◽  
David Alan Bond ◽  
Alex Francisco Herrera ◽  
Kami J. Maddocks ◽  
...  
Keyword(s):  
Phase 1 ◽  
Safety Data ◽  
Standard Of Care ◽  
Primary Objective ◽  
Clinical Activity ◽  
Newly Diagnosed ◽  
Grade 5 ◽  
Unrelated Condition ◽  
Mantle Cell ◽  
Grade 3

7505 Background: MCL is a rare lymphoma without a standard of care but several regimens have demonstrated clinical activity, the majority based on traditional chemotherapy. We hypothesized that adding venetoclax (V) to R2 would be safe and effective in MCL pts irrespective of age, morphology or stage. Here we present safety and efficacy data from the on-going phase 1b study of R2 + V in pts with newly diagnosed MCL. Methods: This multi-center phase 1 study (NCT03523975) enrolled pts aged ≥18 yrs with untreated MCL. The primary objective was to characterize the safety and tolerability of R2 + V and determine the MTD. During induction (12 months (m)) pts received lenalidomide (L) 20 mg daily on day 1-21, Rituximab (R) was given weekly during c1 then on day 1 of every even cycle, V was escalated over 4 weeks to 400 mg beginning day 8. Each cycle is 28 days (d). The DLT period was 42 d beginning C1D8. In maintenance, R every 8 weeks for 36m, L at 10 mg or half of last dose during induction for 24 m and V for minimum 12 m. No pts have been transplanted. Pts with progression (PD) came off study. MRD was analyzed in parallel with scans during induction by clonoSEQ assay (Adaptive Biotechnologies). Results: As of Feb. 1st, 2021, we have enrolled all 28 planned pts on study. Pt characteristics/responses are summarized in Table. Among the 28 pts who have received at least one dose, the median treatment duration so far is 278d (IQR 170-560), with 24 pts still on treatment (Tx). 1 pt is off from a unrelated condition. All pts escalated to V 400 mg w/o any DLTs noted. Treatment-emergent adverse events (TEAEs) were reported in 100% of pts, and grade 3+ TEAEs were reported in 26 (93%) patients. The most common all-grade TEAEs (≥50% of pts), regardless of relationship to study Tx, were fatigue, neutropenia and diarrhea. Grade ≥3 TEAEs reported in ≥50% pts were neutropenia (68%) and thrombocytopenia (50%). No pts have withdrawn or d/c Tx due to AEs. There was one grade 5 event, in a non-evaluable pt, related to a PE that occurred prior to DLT period. In the 28 evaluable pts the ORR (CR/PR) was 96% (27/28 pts) with CR/CRu of 89%. Of the responding pts, two had PD, one w/ CR and one w/ PR. All pts with PD had baseline TP53 mutation. MRD testing was successful in all pts. At time of submission 20 of 28 (71%) were MRD - at 10-6. Conclusions: Interim results show that at the MTD the combination of V 400 mg daily, L 20 mg, with R is safe with a manageable toxicity profile and a high ORR and MRD - in pts with newly diagnosed MCL. Safety data is consistent with the AE profile noted for each drug without any unexpected or unique AEs. Updated results including BH3 profiling will be presented at the meeting. Clinical trial information: NCT03523975. [Table: see text]

Phase (Ph) 1b/2 evaluation of olaratumab in combination with gemcitabine and docetaxel in advanced soft tissue sarcoma (STS).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11517-11517
Author(s):  
Steven Attia ◽  
Victor Manuel Villalobos ◽  
Nadia Hindi ◽  
Brian Andrew Van Tine ◽  
Andrew J. Wagner ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Objective Response ◽  
Locally Advanced ◽  
Primary Objective ◽  
Clinical Activity ◽  
Parameter Estimates ◽  
Second Line ◽  
Line Therapy ◽  
Significant Difference ◽  
Ecog Ps

11517 Background: Doxorubicin (doxo) remains standard first-line therapy for advanced STS. Doxo in combination with olaratumab (O) demonstrated superior clinical activity compared to doxo alone in a Ph 2 trial (NCT01185964), although this was not confirmed in the subsequent Ph 3 trial (NCT02451943). Gemcitabine (G) plus docetaxel (D) is a second line therapy for advanced STS. Here, we report a concurrent Ph 2 study that explored a second-line addition of O to G and D for advanced STS (ANNOUNCE 2 NCT02659020). Methods: Adult patients (pts) with unresectable locally advanced or metastatic STS, ≤ 2 prior lines of systemic therapy, and ECOG PS 0-1 were eligible. Pts were enrolled from 2 cohorts: O-naïve and O-pretreated. In both cohorts, pts were randomized 1:1 to either O, G plus D or placebo (PBO), G plus D. Pts received 21-day cycles of O (20 mg/ kg cycle 1 and 15 mg/kg other cycles, day (d) 1 and d8), G (900 mg/m2, d1 and d8) and D (75 mg/m2, d8). Pts continued treatment until progression, toxicity, or withdrawal. Randomization was stratified by histology (leiomyosarcoma [LMS] vs non-LMS), prior systemic therapy, ECOG PS, and prior pelvic radiation. The primary objective was overall survival (OS) in the O-naïve population using an alpha level of 0.20. Secondary endpoints included OS (O-pretreated) and other efficacy parameters, as well as safety and pharmacokinetics (PK). Results: 167 pts were enrolled in the O-naïve cohort and 89 pts in the O-pretreated cohort. Baseline patient characteristics were well balanced. OS for O-naïve pts was 16.8 vs 18.0 months (m) (hazard ratio [HR] = 0.95, 95% CI: 0.64-1.40; p = 0.78) for the investigational vs control arm, respectively. Other efficacy outcomes are presented in the table. Safety was manageable across treatment arms. PK parameter estimates for O were consistent with previous studies. Conclusions: There was no statistically significant difference in OS between the two arms in the O-naïve population. However, while not statistically significant, the combination of O, G and D demonstrated favorable OS in the O-pretreated cohort, and PFS and objective response rate (ORR) in both cohorts. For O-naïve pts, a clinically meaningful progression-free survival (PFS) improvement was observed. Further investigations in specific histological subtypes are ongoing. Clinical trial information: NCT02659020. [Table: see text]

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

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

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

Modified FOLFOX in combination with docetaxel for patients with metastatic adenocarcinoma of the stomach or gastroesophageal junction: A multicenter phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4545-4545 ◽  
Author(s):  
S. Al-Batran ◽  
J. T. Hartmann ◽  
R. Hofheinz ◽  
R. Mahlberg ◽  
N. Homann ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Survival Data ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Hematologic Toxicity ◽  
Toxicity Profile ◽  
Metastatic Adenocarcinoma ◽  
Grade 3 ◽  
Almost All ◽  
Ecog Ps

4545 Background: The combination of docetaxel, cisplatin, and fluorouracil (DCF) is clearly superior to CF in the treatment of patients (pts) with advanced gastric cancer (AGC). DCF is, however, associated with significant toxicity, including neutropenia, febrile neutropenia, diarrhea and mucositis. This study evaluated a biweekly, oxaliplatin-based modification of DCF. Methods: Pts with measurable, locally advanced or metastatic adenocarcinoma of the stomach or GE-junction and no prior chemotherapy received mFOLFOX (oxaliplatin 85 mg/sqm, leucovorin 200 mg/sqm, and fluorouracil 2.6 g/sqm via 24hr infusion) in combination with docetaxel 50 mg/sqm on day 1 every 2 weeks (FLOT-regimen). Prophylactic G-CSF was not administered. Overall response rate (RR) was the primary endpoint (power 80% to detect a RR of >40%) and toxicity profile the main secondary endpoint. The study was externally monitored according to GCP and data were reviewed by an independent safety board. Results: 59 pts (male, 41; female, 18) were enrolled. At the time of analysis, 53 pts were evaluable for toxicity and 51 pts for response. Median age was 60 (range, 29–76), median ECOG PS was 1, and almost all (93%) pts had metastatic disease. Of 51 pts, 2 had a CR and 25 pts attained a PR, adding to an overall RR of 53% (ITT-analysis). Stable disease was observed in 12 (23.5%) and progressive disease in 6 (11.8%) pts. Six (11.8%) pts were not evaluable for response. NCI-CTC grade 3 or 4 hematologic toxicity included leukopenia in 12 (22.6%), neutropenia in 23 (43%), and anemia in 2 (3.8%) pts. Febrile neutropenia was observed in 1 (1.9%) pt only. Other grade 3 or 4 toxicities included peripheral neuropathy in 4 (7.5%), nausea in 3 (5.7%), vomiting in 2 (3.8%) as well as diarrhea and fatigue in 5 (9.4%) pts each. No treatment related deaths were observed. Conclusions: FLOT is active and has a favorable toxicity profile in the treatment of pts with AGC. It may show activity also in perioperative treatment settings and may be considered as a useful treatment option for elderly pts. Survival data will be presented at the meeting. [Table: see text]

Cetuximab in combination with chemoradiotherapy prior to surgery in patients with resectable, locally advanced esophageal carcinoma: A prospective, multicenter phase lb-ll trial of the Swiss Group for Clinical Cancer Research (SAKK 75/06)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4570-4570
Author(s):  
T. Ruhstaller ◽  
M. Pless ◽  
J. C. Schuller ◽  
H. Kranzbühler ◽  
R. von Moos ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Phase Ii ◽  
Phase 1 ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiation ◽  
Thoracic Esophagus ◽  
Clinical Cancer Research ◽  
Intention To Treat ◽  
Grade 3

4570 Background: Cetuximab significantly enhances efficacy of radiotherapy and chemotherapy in head and neck cancer. We investigated the safety and feasibility of adding cetuximab to neoadjuvant chemoradiation of locally advanced esophageal cancer. Methods: Pts with resectable, locally advanced squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the thoracic esophagus or gastroesophageal junction (staged by EUS, CT and PET scan) were treated with 2 cycles of induction chemotherapy (docetaxel 75mg/m2, cisplatin 75mg/m2 q3w and weekly cetuximab 250mg/m2), followed by concomitant chemo- immuno-radiation therapy (CIRT: docetaxel 20mg/m2, cisplatin 25mg/m2 and cetuximab 250mg/m2 weekly five times concomitant with 45 Gy radiotherapy in 25 fractions); followed by surgery 4–8 weeks later. The phase I part consisted of 2 cohorts of 7 patients each, without and with docetaxel during CIRT, respectively. Interpatient dose-escalation (adding docetaxel during CIRT) was possible if < 2 out of 7 pts of the 1st cohort experienced limiting toxicity. Having finished the phase 1 part, 13 additional patients were treated with docetaxel-containing CIRT in a phase II part. Pathological response was evaluated according to the Mandard classification. Results: 27 pts from 12 institutions were included. As of today, results from 20 pts are available (cohort 1: 7, cohort 2: 7, phase ll : 6). Median age was 64yrs (range 47–71). 11 AC; 9 SCC. 19 pts (95%) completed CIRT (1 pt stopped treatment during induction therapy due to sepsis). 17 pts underwent resection (no surgery: 1pt for PD, 1pt for cardiac reasons). Grade 3 toxicities during CIRT included anorexia 15%, dysphagia/esophagitis 15%, fatigue 10%, nausea 10%, pruritus 5%, dehydration 5%, nail changes 5% and rash 5% .1 pt suffered from pulmonary embolism. 13 pts (65%, intention-to-treat) showed a complete or near complete pathological remission (cohort 1: 5, cohort 2: 4, phase II: 4). Conclusions: Adding cetuximab to preoperative chemoradiation for esophageal cancer is safe and feasible in a community-based multicenter setting. Antineoplastic activity is encouraging with 65% pathological responders. [Table: see text]

Efficacy and tolerability of bevacizumab (BEV) plus capecitabine and cisplatin (XP) in Chinese patients (pts) with locally advanced or metastatic gastric/gastroesophageal junction cancer (AGC): Results from the AVATAR study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 73-73 ◽  
Author(s):  
Lin Shen ◽  
Jin Li ◽  
Jian-Ming Xu ◽  
Hong-Ming Pan ◽  
Guanghai Dai ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Chinese Patients ◽  
Double Blind Study ◽  
Double Blind ◽  
Gastroesophageal Junction Cancer ◽  
The Difference ◽  
Grade 3

73 Background: In the AVAGAST study, chemotherapy (fluoropyrimidine and cisplatin) + BEV did not significantly improve overall survival (OS) vs. chemotherapy + placebo. Geographic differences in efficacy were observed, but only 12 Chinese pts were included. AVATAR, a study similar in design to AVAGAST, is a randomized double-blind study conducted exclusively in China in pts with AGC. Methods: Pts aged >18 years with gastric adenocarcinoma were randomized 1:1 to XP + BEV 7.5 mg/kg or placebo + XP. The primary objective was OS; secondary objectives included progression-free survival (PFS) and safety. Results: Baseline characteristics of the 202 pts were well balanced. The primary efficacy endpoint of improved OS in the BEV arm was not met (HR 1.11, 95% CI 0.79–1.56; p=0.5567; see table ). BEV + XP was well tolerated. Grade 3–5 adverse events (AEs) and serious AEs were 60% and 19% for BEV and 68% vs. 21% for placebo, respectively. Grade 3–5 AEs of special interest with BEV occurred in 8% of BEV pts and 15% of placebo pts; the difference was mainly due to grade 3–5 haemorrhage (BEV 4%, placebo 12%). Conclusions: Addition of BEV to XP in Chinese pts with AGC did not significantly improve outcomes in AVATAR. The results from AVATAR are consistent with the findings seen in the Asian sub-population of the previous AVAGAST study. [Table: see text]

Pharmacokinetics and safety of an oral ALK inhibitor, ASP3026, observed in a phase I dose escalation trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2602-2602 ◽  
Author(s):  
Amita Patnaik ◽  
Patricia LoRusso ◽  
Howard A. Ball ◽  
Erkut Bahceci ◽  
Geoffrey Yuen ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Dose Escalation ◽  
Phase 1 ◽  
Single Agent ◽  
Clinical Activity ◽  
Expansion Phase ◽  
Advanced Malignancies ◽  
Grade 3 ◽  
Ecog Ps ◽  
Clinical Trial Information

2602 Background: ASP3026 (3026) is a selective, potent, ATP-competitive, small molecule oral inhibitor of ALK receptor tyrosine kinase that has not previously been tested in humans. A Phase 1 dose-escalation trial, using a 3+3 design, evaluating 3026 as an oral single agent was conducted to investigate PK (Day 1 and Day 28), safety and clinical activity in patients (pts) with advanced malignancies (excluding leukemias) of ECOG PS 2 or less. Methods: 3026 was administered under fasting conditions on a continuous schedule to pts in successive dose-escalating cohorts at doses ranging from 25 mg QD to 800 mg QD. Results: Thirty pts were enrolled into the dose escalation part of the study. The MTD was determined based on DLT data from cycle 1. Three DLTs were observed: grade 2 nausea and vomiting leading to dose reduction at 525 mg QD; grade 3 rash leading to dose reduction, and grade 3 ALT/AST increase leading to study withdrawal at 800 mg QD. The most common AEs were constipation, vomiting, diarrhea, nausea and abdominal pain, and all AEs were manageable and reversible. Median AUC and Cmax increased proportionally with dose from 25 mg QD to 800 mg QD. There was no evidence of non-linear PK at ASP3026 doses >25 mg QD. The median terminal half-life was approximately 10 - 41 hours. Overall, A3026 appears well absorbed with median Tmax around 3 hours for both Day 1 and Day 28. Terminal T1/2 appears adequate for one daily dosing with median values ranging from approximately 18 to 34 hours. Based on visual inspection of pre-dose (trough) values from Days 8, 15, 22, and 28 it appears that steady-state conditions are achieved by day 28. Conclusions: The MTD of 3026 is 525 mg QD. Treatment with 3026 resulted in a promising safety and PK profile in pts with advanced malignancies. Further evaluation of 3026 in pts with tumors harboring gene mutation or ALK fusion genes in the cohort expansion phase at the MTD is ongoing. Clinical trial information: NCT01401504.

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