Final toxicity results from a phase II study of 5-fluorouracil, oxaliplatin, and dasatinib (FOLFOX-D) in previously untreated metastatic pancreatic adenocarcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 504-504
Author(s):  
Thomas J. George ◽  
Jason Scott Starr ◽  
Hiral D. Parekh ◽  
Alison Marguerite Ivey ◽  
Long H. Dang ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Circulating Tumor Cell ◽  
Target Lesion ◽  
Primary Objective ◽  
Investigation Methods ◽  
Clinical Benefits ◽  
Ecog Ps

504 Background: Systemic chemotherapy for pancreatic adenocarcinoma (PCa) improves survival but most targeted agents have consistently failed to demonstrate clinical benefits. Src is overexpressed in PCa and promotes an aggressive cancer phenotype. Dasatinib (D) is an oral multi-tyrosine kinase inhibitor (TKI) affecting tumor proliferation through inhibition of Src, Bcr-Abl, CKit and other pathways. Inhibition of Src is associated with biologic modifications favorably modifying the PCa phenotype and has synergy with restoring inherent chemosensitivity. Src inhibition can also increase oxaliplatin activity and modulate Tcell responses. The addition of D to the well-established backbone of FOLFOX represents a multifaceted line of scientific investigation. Methods: This single arm phase II trial is to determine activity and toxicity of FOLFOX + D in previously untreated metastatic PCa. Pts must have at least 1 RECIST measurable target lesion, ECOG PS 0-2, normal QTc and adequate organ function. Treatment is standard q14d cycles of mFOLFOX6 with continuous D (150mg PO daily). Tumor assessments occur q8w. Endpoints are PFS (primary), objective and biochemical response rates, clinical benefit rate, freedom from metastases, overall survival (OS), toxicity, and quality of life. Exploratory tissue, circulating tumor cell and serum analyses to identify predictors of response are planned, particularly in those with durable disease control or exceptional response. Sample size is based on a 50% improved median PFS from 4 (historical) to 6 months. Results: Enrollment is now closed on this prospective phase II study with 42 of 42 evaluable pts. Baseline demographics are in Table 1. Toxicity and outcomes continue to be assessed. Conclusions: Final toxicity data will be presented at the meeting for this novel combination treatment in advanced PCa. Clinical trial information: NCT01652976. [Table: see text]

5-fluorouracil, oxaliplatin and dasatinib (FOLFOX-D) for previously untreated metastatic pancreatic adenocarcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS517-TPS517
Author(s):  
Thomas J. George ◽  
Long H. Dang ◽  
Karen Colleen Daily ◽  
Jason Scott Starr ◽  
Hiral D. Parekh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Circulating Tumor Cell ◽  
Target Lesion ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Investigation Methods ◽  
Cancer Phenotype

TPS517 Background: Systemic chemotherapy for pancreatic adenocarcinoma improves survival and cancer related symptoms. Most targeted agents combined with gemcitabine have consistently failed to demonstrate clinical benefits. Src is overexpressed in pancreatic cancer and promotes an aggressive cancer phenotype. Dasatinib (D) is an oral multi-tyrosine kinase inhibitor (TKI) affecting tumor proliferation through inhibition of Src, Bcr-Abl, CKit and other pathways. Inhibition of Src is associated with biologic modifications favorably modifying the pancreatic cancer phenotype and has synergy with restoring inherent chemosensitivity. Src inhibition can also increase oxaliplatin activity and modulate Tcell responses. The addition of D to the well-established backbone of FOLFOX represents a multifaceted line of scientific investigation. Methods: This is a multicenter phase II trial to determine activity and toxicity of FOLFOX + D in previously untreated metastatic pancreatic adenocarcinoma. Eligible pts must have at least 1 measurable target lesion by RECIST, ECOG PS 0-2, normal QTc and adequate organ function. Pts received standard cycles of mFOLFOX6 repeated q14d with continuous D (150mg PO daily). Tumor assessments occur q8w. Endpoints included progression-free survival (primary; PFS), objective and biochemical response rates, clinical benefit rate, freedom from metastases, overall survival (OS), toxicity, and quality of life. Exploratory tissue, circulating tumor cell and serum analyses to identify predictors of response are planned, particularly in those demonstrating durable disease control or exceptional response. Sample size was based on a 50% improved median PFS from 4 (historical) to 6 months. NCT01652976. Results: Enrollment continues on this prospective phase II study with 38 of 42 evaluable patients. There are no unexpected toxicities noted thus far. Clinical trial information: NCT01652976. [Table: see text]

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]

Final results of phase II study of S-1, oral leucovorin, oxaliplatin, and bevacizumab combination therapy (SOL+BV; SOLA) in metastatic colorectal cancer (mCRC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 574-574 ◽  
Author(s):  
Kentaro Yamazaki ◽  
Tomohiro Nishina ◽  
Takeshi Kato ◽  
Takayuki Yoshino ◽  
Yoshinori Miyata ◽  
...  
Keyword(s):  
Survival Rate ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Present Report ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Target Lesion ◽  
Ecog Ps ◽  
The Impact

574 Background: The SOL regimen (S-1, Oral Leucovorin; LV, and Oxaliplatin) demonstrated a promising activity with tolerated toxicities compared to mFOLFOX6 in a randomized phase II study for mCRC. We previously reported the promising results of a phase II study of SOL+BV in Gastrointestinal Cancers Symposium 2012 (Kato T, et al.) focusing on early clinical outcomes, overall response rate (ORR), progression free survival (PFS) and safety. The final follow-up (cut-off date Dec 2012) has been completed, and we report up-dated overall survival (OS) and the impact of early objective tumor response (EOTR) on OS in the present report. Methods: The main inclusion criteria were; (1) metastatic colorectal adenocarcinoma, (2) age ≥20 years, (3) no prior chemotherapy, (4) target lesion (RECIST v1.0), (5) ECOG PS 0-1, 6) written informed consent. Patients (pts) received S-1 (40-60 mg bid) and LV (25 mg bid) orally for one week. Oxaliplatin (85 mg/m2) and BV (5 mg/kg) were administered on day 1. This treatment was repeated every 2 weeks. The primary endpoint was ORR confirmed by the independent review committee according to RECIST v1.0. This trial was supported by Taiho Pharmaceutical CO, LTD. (JAPIC Clinical Trials information Identifier: JapicCTI-090881). Results: From Oct 2009 to Apr 2010, 31 pts were enrolled. Of the eligible 29 pts, median age was 62; PS 0/1 was 24/5; number of metastatic organs 1/≥2 was 15/14. ORR was 86% (95%CI, 68-96), and the median PFS was 15 months (95%CI, 10-26). OS has not reached median with a median follow-up time of 34 months. Two-year survival rate was 72%. EOTR (RECIST sum ≥30% shrinkage) at 6-weeks was observed in 35% of pts. Two-year survival rate in these pts with an EOTR at 6-weeks was 80%, while in other pts without an EOTR at 6-weeks was 68%. The curative resection rate of metastatic lesions was 28%. The incidence (≥10%) of grade 3/4 adverse drug reactions were; neutropenia 20%, hypertension 23%, anorexia 20%, fatigue 17%, diarrhea 10%, and sensory neuropathy 53%. Conclusions: The SOL+BV regimen showed the promising activity for mCRC. The high proportion of EOTR might lead to long survival. Further evaluation of this regimen would be warranted. Clinical trial information: 090881.

Gefitinib plus celecoxib in chemotherapy-naïve patients with stage IIIB/IV non-small cell lung cancer (NSCLC): A phase II study from the Hoosier Oncology Group

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7066-7066 ◽  
Author(s):  
A. K. Agarwala ◽  
L. Einhorn ◽  
W. Fisher ◽  
D. Bruetman ◽  
J. McClean ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Day Treatment ◽  
Single Agent ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Stage Iiib ◽  
Never Smokers ◽  
Ecog Ps

7066 Background: Gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) pathway, has single agent activity in NSCLC. Preclinical studies demonstrate significant interactions between the EGFR and cyclo-oxygenase 2 (COX-2) pathways and that simultaneous inhibition against NSCLC may have benefits over gefitinib alone. Methods: Eligibility required that pts were chemotherapy-naïve, had stage IIIb (with pleural effusion) or IV NSCLC and an ECOG PS 0–1. Pts received gefitinib 250mg orally daily plus celecoxib 400mg orally every 12 hours. Cycles consisted of 21 day treatment and continued until unacceptable toxicity or progression of disease. The primary objective of this single arm, two-stage, phase II study was to evaluate the overall response rate. If ≤ 10 out of 30 pts achieved a complete (CR) or partial response (PR), the study would be stopped early. If >10 out of 30 pts had a CR or PR, enrollment would continue to 50 pts. Results: From 1/04 to 11/04, 31 pts were enrolled: male/female 13/18; median age 70.8 years (range, 19–93); 67.7% had adenocarcinoma; ECOG PS 0/1 13/18; stage IIIb/IV 2/29; 5 were current smokers, 9 were remote (>30 years) or never smokers, 16 quit smoking > 3 months ago. Median number of cycles was 4 (range, 0–16). 6 pts (19.4%) discontinued therapy due to toxicity, including 3 who died due to treatment. Select grade 3/4 toxicities included: pulmonary (6.5%), hepatic (6.5%), diarrhea (6.5%), skin (3.2%). Responses included PR 5 (16.1%), stable disease 8 (25.8%), and progressive disease 18 (58.1%). Median duration of response, progression free survival, and overall survival was 5.7, 2.8, and 7.2 months, respectively. All responders were females with adenocarcinoma, 2 were remote or never smokers and 3 were former smokers. Conclusion: Gefitinib plus celecoxib in an unselected population of chemotherapy naïve patients with advanced NSCLC and a PS of 0–1 has a lower response rate and overall efficacy compared with historical controls of chemotherapy. [Table: see text]

A phase II study of capecitabine (CAP) plus PHY906 in patients (pts) with advanced pancreatic cancer (APC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15508-e15508 ◽  
Author(s):  
M. W. Saif ◽  
J. Li ◽  
L. Lamb ◽  
A. Rosenberg ◽  
K. Elligers ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Advanced Pancreatic Cancer ◽  
Dose Intensity ◽  
Primary Objective ◽  
Second Line ◽  
Nf Kappa B ◽  
Gm Csf ◽  
Gi Symptoms ◽  
Ecog Ps

e15508 Background: Gemcitabine (G) is regarded as the standard treatment for pts with APC. However, a standard second-line chemotherapy regimen has yet to be defined after G. PHY906, a 4-herb traditional Chinese medicine has a history of > 1,800 yrs of human use to treat GI symptoms including diarrhea. Preclinical studies showed that PHY906 may potentiate antitumor activity of CAP in human PANC-1 xenograft (ASCO 2007). A phase I study showed that CAP can be escalated up to 1750 mg/m2 PO BID on d1- 7 and PHY906 800mg PO BID on d1–4 q 2 wks with no DLTs (ASCO, 2008). Delivered dose-intensity of CAP was similar at 1750mg/m2 dose level as 1500mg/m2. Therefore, 1500mg/m2 of CAP and PHY906 was further tested in a phase II study as second-line treatment in pts with APC. Methods: Pts with G-refractory APC with ECOG PS <2 were treated with CAP 1500mg/m2 d1–7 with PHY906 800mg d1–4 q 2 wks. Response was assessed by CT scan according to RECIST q 6 wks and toxicity according to NCI-CTC v3.0. Primary objective is overall survival. Secondary objectives include overall RR, PFS and measurement of cytokines to assess inhibition of NF-kappa B, a possible mechanism responsible for PHY906's pharmacological activity. Results: As of January 5, 2009, 25 pts have been enrolled. Baseline characteristics include median age, 65 (range, 40–85); male/female,15/10; ECOG PS 0/1, 4/19; median cycles: 3 (r: 0.5–15). At this point 5 pts are still in active treatment. 4 pts have confirmed OS > 6 ms (1 still on study) with 2 further pts approaching 6 ms. Among evaluable pts, 1 had PR (5.3%), 11 SD (57.9%) and 7 PD (36.8%) after initial restaging scan. 36 % pts had >30% reduction in CA19–9 as biochemical response. There were 7 deaths on/within 30 days of study treatment, 6 related to PD and 1 had acute MI. G3/4 toxicities diarrhea 3/25 (12%), fatigue, 1/25 (4%), HFS 1/25 (4%) and mucositis 1/25 (4%). 1 pt was removed from study due to G3 HFS. Biomarker studies (IL4, GM-CSF, TNF-alpha, IL10, MCP-1, IL2, IL6) are ongoing. Conclusions: This is the first clinical study to evaluate a botanical formulation PHY906 with CAP in G-refractory APC pts. CAP + PHY906 regimen appears a safe and feasible salvage therapy in APC and warrants further investigation. In addition, PHY906 may have a cytoprotective antidiarrheal and anti-HFS effect, making treatment with CAP more tolerable. [Table: see text]

Prospective phase II study of inoperable pancreatic adenocarcinoma with neoadjuvant gemcitabine, docetaxel, and capecitabine (GTX).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 274-274
Author(s):  
Anthony Paul Gulati ◽  
Stephen M. Schreibman ◽  
Beth Schrope ◽  
James A. Lee ◽  
John Allendorf ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Phase Ii Study ◽  
Primary Objective ◽  
Unresectable Pancreatic Cancer ◽  
Prospective Phase ◽  
Similar Survival ◽  
Grade 3 ◽  
Ecog Ps ◽  
Clinical Trial Information

274 Background: Chemoradiation (CRT) is used in unresectable pancreatic cancer (PC) to convert patients to a resectable state. Those who go to surgery can have a similar survival as those initially deemed resectable, with a mOS of 8.2-9 mo. We recently reported a prospective phase II trial of our synergistic regimen (GTX) for patients with metastatic PC with a mOS of 14.7 mo. Methods: 35 patients with ECOG PS 0-2 and completely unresectable advanced PC (localized to the pancreas, small bowel, stomach and/or encasing at least 2 vessels such as the SMA, CA, HA, PV, or SMV) were treated with GTX: Capecitabine (Xeloda) PO 1500mg/m2 divided into 2 doses daily on days 1-14, gemcitabine 750mg/m2 IV given over 75 min on days 4 & 11, docetaxel 30mg/m2 IV infusion over 30 minutes preceded by dexamethasone 10mg IV/PO on days 4 & 11, in a 21 day cycle. 3 cycles were given before evaluation. If eligible, a patient was allowed to proceed to surgery without radiation. Otherwise, starting on week 12, 5040 cGy of conformal radiation was given over 5-6 weeks (Mon-Fri) with weekly gemcitabine 250-300mg/m2 IV infusion over 30 min. No adjuvant treatment was given on protocol. Primary objective was conversion rate to operable status, and secondary objectives included RR (based upon RECIST), OS, and PFS. Results: Duration of neoadjuvant chemotherapy was 9 weeks and 0% showed POD during this time. 20 of 35 patients (57%) became eligible for surgery. Of all 35 patients, there was a 49% rate of negative margins at surgery (in 85% of those patients who underwent surgery). 23 patients (66%) underwent CRT, and 11 of them (48%) ultimately went to surgery and had clean margins. Median OS from initiation of chemotherapy for all patients was 17.4 mo and >22 mo if they went to surgery (20/35 pts, 1 alive). PFS of patients who underwent surgery was 13.2 mo. Grade 3/4 toxicities primarily included neutropenia (25%), leukopenia (11%), and diarrhea (6%). No deaths were attributed to GTX. Conclusions: Neoadjuvant GTX +/- radiation with gemcitabine can be used as an effective treatment for patients with truly unresectable PC. Clinical trial information: NCT00869258.

A phase II trial of the effect of perindopril on hand foot syndrome (HFSR) incidence and severity in patients receiving regorafenib with refractory metastatic colorectal carcinoma (mCRC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 824-824
Author(s):  
Barbara L. Melosky ◽  
Howard John Lim ◽  
Janine Davies ◽  
Sharlene Gill ◽  
Christian K. Kollmannsberger ◽  
...  
Keyword(s):  
Phase Ii ◽  
Interim Analysis ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Capillary Endothelium ◽  
Open Label ◽  
Grade 3 ◽  
Overall Survival Benefit ◽  
Ecog Ps

824 Background: Regorafenib is an oral multi-kinase inhibitor (MKI), with a demonstrated overall survival benefit in mCRC refractory to standard therapy ( PMID 23177514). The most common grade 3 adverse event (AE) reported in this trial was HFSR, with 47% of patients (pts) experiencing HFSR of all grades, and 17% with grade 3 severity. The pathogenesis of regorafenib-induced HFSR is not well established, but may be related to alterations in the capillary endothelium. Perindopril is an Angiotensin Converting Enzyme (ACE) Inhibitor indicated for the treatment of hypertension, and may also play a role in preventing endothelial dysfunction ( PMID 17140552). We hypothesized that perindopril may prevent or reduce the severity of regorafenib-induced HFSR. Methods: In this single center Phase II, open label trial, 34 pts with refractory mCRC were planned to be treated with regorafenib (160 mg/day) and perindopril (4 mg/day) with both agents given 3 weeks on and 1 week off. An interim analysis was planned after 10 evaluable pts. The primary objective was to assess the proportion of pts with any grade HSFR toxicity. Secondary endpoint included time to development of worst (grade 3) HSFR toxicity, proportion of all grades of hypertension and all grade toxicities, and progression free survival. All toxicities were evaluated using CTCAE v4.03. Results: 12 pts were accrued over a 9 month time period, and 10 pts were considered evaluable as they completed one cycle of treatment. Pt characteristics included (6 M/ 6F, mean age 62, ECOG PS 0 (25%)/ 1 (75%). A planned interim analysis was performed after 10 evaluable pts had completed their first cycle of study treatment. 5/10 (50%) experienced Grade 3 HFSR, and based on the statistical plan it was deemed highly unlikely that perindopril would lead to reduced levels of regorafenib induced HSFR compared with regorafenib alone thus enrolment was stopped. The most frequent other grade 3 toxicities included hypertension (16.7%), and increased AST (16.7%). Conclusions: The addition of perindopril to regorafenib did not appear to reduce HSFR incidence and severity in pts with refractory mCRC. Clinical trial information: NCT02651415.

Pembrolizumab in patients with recurrent thymic carcinoma: Results of a phase II study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8573-8573 ◽  
Author(s):  
Giuseppe Giaccone ◽  
Jillian Thompson ◽  
Colleen McGuire ◽  
Maria Manning ◽  
Bhaskar Kallakury ◽  
...  
Keyword(s):  
Phase Ii ◽  
Thymic Carcinoma ◽  
Residual Disease ◽  
Phase Ii Study ◽  
Treatment Options ◽  
Squamous Carcinoma ◽  
Complete Response ◽  
Primary Objective ◽  
Eligibility Criteria ◽  
Ecog Ps

8573 Background: There are few treatment options for thymic carcinoma after chemotherapy. We completed a single institution phase II study of pembrolizumab (P) in patients with recurrent thymic carcinomas. Methods: Main eligibility criteria included: progression after ≥ 1 chemotherapy line, ECOG PS 0-2, no history of autoimmune disease, and adequate organ function. P was given at 200mg IV every 3 weeks. The primary objective of the study was response rate (RR) by RECIST v1.1 criteria; secondary objectives were PFS and OS, and safety. Results: From 3/2015 to 12/2016 we accrued 41 patients. Of 40 eligible patients, 29 were male, 19 Caucasians, median age was 57 years (range 25-80), 14 had squamous carcinoma histology, and 19 ECOG PS 0. Median number of cycles delivered was 6 (range 1-31). The most common side effects were mild fatigue (10), diarrhea (4) and rhinorrhea (4). Six patients developed multiple grade 3-4 immune-relates AEs (irAEs): myocarditis/myositis (1), myositis/myocarditis/hepatitis/myasthenia gravis (1), myositis/hepatitis (1), bullous pemphigoid (1), hepatitis (1), hepatitis/pancreatitis/diabetes mellitus type 1 (1). There were no treatment related deaths. The 2 patients who developed myocarditis required a pacemaker. Three patients interrupted treatment because of irAEs (all responders) and 3 because of progression around the time of the irAE. irAEs were more frequent in females (4/6; p = .026). Five patients developed hypothyroidism and 1 hyperthyroidism. RR assessed in all 40 eligible patients was 22.5%: 1 complete response, 8 partial responses (plus 1 unconfirmed), 20 stable disease and with 11 progressions. Two partial responses show minimal residual disease with no PET uptake. Two responders have progressed and 5 responses are beyond 12 months duration. Of 29 cases tested for PD-L1 staining (Dako 22C3), high PD-L1 (≥50% tumor cells positive) was seen in 8 (28%); 6/9 responders had high PD-L1 expression. Targeted NGS in 15 cases did not show correlation between mutational burden and response. Conclusions: P has activity in patients with thymic carcinoma. irAEs are more frequent than in other tumors. Further analysis of NGS, Nanostring and PD-L1 expression and updated survival will be presented. Clinical trial information: NCT02364076.

A phase II study of vorolanib (CM082) in combination with toripalimab (JS001) in patients with advanced mucosal melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10040-10040 ◽  
Author(s):  
Lu Si ◽  
Xinan Sheng ◽  
Lili Mao ◽  
Caili Li ◽  
Xuan Wang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Mucosal Melanoma ◽  
Clinical Activity ◽  
Effective Treatment Option ◽  
Grade 3 ◽  
Ecog Ps

10040 Background: Vorolanib (CM082) is a multi-target tyrosine kinase inhibitor including VEGF, PDGF, c-kit, and Flt-3. Toripalimab (JS001) is a humanized IgG4 mAb against programmed death-1 (PD-1) with clinical activity in metastasis melanoma but not in its mucosal subtype. In this phase II study (NCT03602547), we investigated the safety and efficacy of CM082 in combination with JS001 in patients (pts) with advanced mucosal melanoma. Methods: The study enrolled pts from 18 to 75 years-old with histologically confirmed metastatic mucosal melanoma, ECOG PS 0-1, no prior systemic anti-cancer treatment. Eligible pts were treated with CM082 tablet (150 or 200 mg once daily) combined with JS001 (240mg every 2 weeks, IV, Q2W) until confirmed disease progression or unacceptable toxicity. Clinical response was evaluated every 8 week. The primary endpoint was overall response rate (ORR) using RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of remission (DOR), and time to first remission (TTR) according to RECIST v1.1 and iRECIST. The safety was also assessed. Results: Between July 2018 and April 12, 2019, 40 pts (19 pts in 150mg group; 21 pts in 200mg group) were enrolled and 38 pts were evaluable for tumor response (150mg n = 18, 200mg n = 20), with 4 (22.2%) confirmed partial response (PR), 6 (33.3%) stable disease (SD) and 8 (44.4%) progression disease (PD) in the 150mg CM082 group; 3 (15%) PRs (including 2 unconfirmed), 10 (50%) SD, and 7 (35%) PD were reported in the 200mg CM082 group. Tumors shrank in 10 pts (56%) in the 150mg group and 10 pts (50%) in the 200mg group. At data cut-off (November 28, 2019), 29 pts had PFS events (150mg n = 12; 200mg n = 17). The median PFS was 5.7 (95% CI 2.0, NE) months and 5.6 (1.9, 7.7) months in the two groups, respectively. The most common treatment-related adverse events (AEs) were grade 1 or 2, including leukopenia, elevated LDH, increased ALT, neutropenia, increased AST, and elevated GGT. Common grade 3 or higher adverse events ( > 10%) were increased ALT (12 pts, 30%), increased AST (11 pts, 27.5%), neutropenia (6 pts, 15%) and elevated GGT (6 pts, 15%). Eight pts had 9 serious AEs (SAEs). The study is still ongoing and more data will be presented in the future. Conclusions: PFS benefit was observed in both 150mg and 200mg subgroups. This study demonstrated potentially improved efficacy with predictable toxicities of CM082 in combination with JS001 therapy, which may be an effective treatment option for pts with advanced mucosal melanoma. Clinical trial information: NCT03602547.

Second line chemotherapy with topotecan and gemcitabine in small cell lung cancer (SCLC) patients: An Alpe-Adria Thoracic Oncology Multidisciplinary group phase II study (ATOM 012)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17014-17014
Author(s):  
O. Belvedere ◽  
C. Sacco ◽  
A. Ardizzoni ◽  
C. Rossetto ◽  
A. Follador ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Moderate Activity ◽  
First Line ◽  
Eligibility Criteria ◽  
Preliminary Results ◽  
Investigation Methods ◽  
Ecog Ps ◽  
Line Chemotherapy

17014 Background: Topotecan is the only single agent currently approved for the treatment of relapsed or recurrent SCLC, showing activity both in chemotherapy-refractory (RR 2–14%) and in chemotherapy-sensitive patients (RR 14–38%). The role of topotecan in combination with other active agents is still under investigation. Methods: Aim of this phase II study is to assess the activity and safety of topotecan (1mg/sqm iv d1–5) plus gemcitabine (1250 mg/sqm iv d1) in relapsed or recurrent SCLC patients. Treatment is repeated every 4 weeks, up to a maximum of 6 cycles. Eligibility criteria: histologically or cytologically confirmed SCLC; documented progressive disease after ≥ 1 chemotherapy regimen; age ≥ 18 yrs; ECOG PS 0–2; measurable disease (RECIST); no prior treatment with topotecan or gemcitabine; adequate hematologic, hepatic and renal function; brain metastases are allowed. Results: A total of 44 patients have been enrolled. Patient characteristics are as follows: median age, 64 yrs (range 35–77); male/female, 35/9; ECOG PS 0/1/2, 12/21/11 patients; 68% patients had sensitive disease (recurrence > 3 months after first-line chemotherapy) and 32% patients had refractory disease (failure ≤3 months after first-line chemotherapy). One-hundred and seventeen chemotherapy courses have been administered (median 2, range 1–6). The following preliminary results refer to 37 patients. Grade 3–4 toxicities: 54% neutropenia, 16% anemia, 46% thrombocytopenia, 13% neutropenic fever, 27% fatigue. One toxic death was observed. Objective responses have been documented in 9 patients, for an overall response rate of 24% (3% CR, 21% PR); SD was observed in 7 patients (19%), PD in 17 patients (46%). Four early deaths were reported. Median time to progression is 8.9 weeks. Median survival time is 16.3 weeks, and 1-year survival rate is 14%. Conclusions: Based on these preliminary results, the combination of topotecan plus gemcitabine shows moderate activity and an acceptable toxicity profile in previously treated SCLC patients. However, it is unlikely that the addition of gemcitabine improves the outcome compared to single agent topotecan. No significant financial relationships to disclose.

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