INMUNOSUN-SOGUG trial: A prospective phase II study to assess the efficacy and safety of sunitinib as second-line (2L) treatment in patients (pts) with metastatic renal cell cancer (RCC) who received immunotherapy-based combination upfront.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5060-5060
Author(s):  
Enrique Grande ◽  
Teresa Alonso Gordoa ◽  
Oscar Reig Torras ◽  
Emilio Esteban ◽  
Daniel Castellano ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Mucosal Inflammation ◽  
Onset Date ◽  
Duration Of Treatment ◽  
Open Label ◽  
Metastatic Rcc

5060 Background: Immunotherapy (IO)-based combinations have replaced tyrosine kinase inhibitors (TKI) as standard upfront treatment of metastatic RCC pts. Selection of 2L treatment after progression to novel combinations in 1st-line (1L) is mostly based on retrospective series or subgroups analysis of randomized trials. We aim to evaluate the activity and safety of sunitinib in advanced RCC after progression on an IO-based 1L approach. Methods: This is a prospective, non-randomized, open-label and multicenter phase II study. Pts with ECOG 0-2 and locally advanced or metastatic RCC after treatment in 1L with a prior PD-1 and/or PD-L1 and/or CTLA-4 inhibitor were included. Sunitinib was administered at 50 mg/day on a 4/2 schedule until disease progression. Primary endpoint was overall response rate (ORR) by RECIST v 1.1 criteria. Results: Twenty pts were enrolled in the study. Median age was 66 yo, 70% had intermediate prognosis by Heng's scale, and 88% ECOG 1. 45% of pts received atezolizumab, 30% pembrolizumab, 20% nivolumab and 15% ipilimumab-based regimens as 1L. ORR to 1L treatment was 45%. Median time from end of 1L to sunitinib onset date was 1.1 months (0.3-22.1). Two (10%) pts had partial response with sunitinib and 11 (55%) stable disease for a total disease control rate of 65%. With a median follow-up of 8.8 months, median PFS was 6.8 months (0.0-13.9) and median OS 13.6 months (10.5-16.6). Median duration of treatment was 4 months (0.9-16-2). Most common treatment-related adverse events, all grades, were asthenia (55%), dysgeusia (35%), diarrhea (30%), hypertension (30%), mucosal inflammation (25%), palmar-plantar erythrodysesthesia (25%), anemia (20%), neutropenia (20%) and nausea (15%); grade 3 were asthenia (15%), hypertension (10%) and neutropenia (10%). Conclusions: To our knowledge, the INMUNOSUN trial is the first study to evaluate prospectively the activity of a single agent TKI in a pure 2L setting of metastatic RCC pts treated with an IO-based approach upfront. ORR and PFS with sunitinib seem lower than expected when used as a 1L. Consistency in toxicity profile was observed. Clinical trial information: NCT03066427 .

Axitinib (AG-013736; AG) in patients (pts) with metastatic renal cell cancer (RCC) refractory to sorafenib

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5032-5032 ◽  
Author(s):  
B. I. Rini ◽  
G. T. Wilding ◽  
G. Hudes ◽  
W. M. Stadler ◽  
S. Kim ◽  
...  
Keyword(s):  
Phase Ii ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Tumor Regression ◽  
Alternative Hypothesis ◽  
Performance Status ◽  
Cell Cancer ◽  
Objective Response ◽  
Open Label ◽  
Metastatic Rcc

5032 Background: Sunitinib and sorafenib, tyrosine kinase inhibitors (TKIs) of the VEGF and PDGF receptors (VEGFR, PDGFR), are FDA-approved treatments for advanced RCC. AG is a potent inhibitor of VEGFRs 1, 2 & 3 and showed substantial efficacy in a previous phase II study in pts with cytokine-refractory RCC (Rini et al. ASCO 2005). The activity of AG in metastatic RCC patients refractory to prior TKI therapy is of interest. Methods: Pts with sorafenib-refractory RCC were enrolled in this multicenter, open-label, phase II study. Eligibility criteria included measurable disease, ECOG performance status of 0 or 1, controlled CNS metastases (if present) and adequate organ function. All pts received a starting dose of AG 5 mg orally BID, titrated according to tolerance. The primary endpoint was RECIST-defined objective response (OR) with a null hypothesis of OR = 8% versus = 20% under the alternative hypothesis. Pts underwent radiographic staging at baseline and every 8 weeks and were treated until progressive disease or unacceptable toxicity. Results: All planned 62 pts have been enrolled. Median age of 42 evaluable pts was 60 years (range 35–77); 29 pts (69%) were male; 41 pts (98%) had prior nephrectomy. Median number of prior therapies was 2 (range 1–8); all pts had received prior sorafenib and 9 pts also received prior sunitinib. Partial response was observed in 6/42 evaluable pts (14%; 95% CI: 5–29%), stable disease in 15 pts (36%), 12 pts (29%) experienced progressive disease, and 9 pts (21%) withdrew due to adverse events. Overall, 57% of pts experienced some degree of tumor regression. With a median follow-up of 5.3 months, the median progression-free survival (PFS) was not reached. Preliminary analysis indicates overall median PFS > 7.1 months. No ORs have yet been observed in patients with prior sunitinib treatment, although tumor regression was demonstrated in 55% of pts with median PFS > 6.1 months. Treatment-related grade 3/4 AEs included hypertension (16%), fatigue (14%) and hand foot syndrome (14%). Overall, 36 pts remain on study. Conclusions: AG has substantial antitumor activity in pts with sorafenib-refractory, metastatic RCC. Toxicity is typical of TKI VEGFR inhibitors and generally manageable. [Table: see text]

scholarly journals Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 39 (9) ◽  
pp. 1020-1028
Author(s):  
David F. McDermott ◽  
Jae-Lyun Lee ◽  
Georg A. Bjarnason ◽  
James M. G. Larkin ◽  
Rustem A. Gafanov ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Clear Cell ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
First Line ◽  
Open Label ◽  
Cell Renal Cell Carcinoma ◽  
Metastatic Rcc

PURPOSE Pembrolizumab, a programmed death 1 inhibitor, demonstrated promising single-agent activity in untreated patients with various cancer types. The phase II KEYNOTE-427 study evaluated efficacy and safety of single-agent pembrolizumab in treatment-naive patients with advanced clear cell renal cell carcinoma (ccRCC; cohort A) and advanced non-ccRCC (cohort B). Results of cohort A are reported. METHODS In this open-label, single-arm phase II study, patients with advanced ccRCC received pembrolizumab 200 mg every 3 weeks for ≤ 24 months. The primary end point was objective response rate by RECIST, version 1.1. RESULTS In the total population (N = 110), median time from enrollment to data cutoff was 35.9 (range, 29.5-40.3) months. Objective response rate was 36.4% with four (3.6%) complete responses and 36 (32.7%) partial responses; disease control rate was 58.2% (95% CI, 48.4 to 67.5). Most patients (68.2%) had a decrease in target lesions, including 30.9% with a reduction ≥ 60%. Median duration of response was 18.9 (range, 2.3-37.6+) months; 64.1% of responders had a response ≥ 12 months (Kaplan-Meier). Median progression-free survival was 7.1 months (95% CI, 5.6 to 11.0). Median overall survival was not reached; 12-month and 24-month overall survival rates were 88.2% and 70.8%, respectively. Durable responses were observed across all International Metastatic RCC Database Consortium categories. Grade 3-5 treatment-related adverse events were reported in 30.0% of patients, of which colitis and diarrhea were most frequent. CONCLUSION Single-agent pembrolizumab showed promising antitumor activity as a first-line treatment in patients with advanced ccRCC, with durable responses across International Metastatic RCC Database Consortium categories. Safety and tolerability profile of pembrolizumab monotherapy was comparable to what has been previously described in other tumor types.

Sunitinib as second-line treatment for advanced gastric cancer: preliminary results from a phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4603-4603 ◽  
Author(s):  
Y. Bang ◽  
Y. Kang ◽  
W. Kang ◽  
N. Boku ◽  
H. Chung ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Mucosal Inflammation ◽  
Open Label ◽  
Preliminary Results ◽  
Grade 3

4603 Background: Sunitinib malate (SU) is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, and FLT3, approved internationally for the treatment of advanced RCC and imatinib-resistant or -intolerant GIST. We investigated the safety and activity of SU monotherapy in pts with previously-treated gastric cancer. Preliminary results from this open-label, multicenter, phase II study are reported. Methods: Eligibility criteria included measurable stage IV disease; 1 prior chemotherapy regimen; and ECOG PS =1. Pts took SU 50 mg/day for 4 wks followed by 2 wks off treatment in 6-wk cycles. A Simon 2-stage design was used with a target accrual of 38 pts in the first stage, expanding to 63 pts if =2 partial responses (PRs) were observed. The primary endpoint was RECIST-defined objective response rate. Secondary endpoints included duration of response and safety. Pharmacokinetic (PK) Ctrough parameters were also monitored. Results: As of Sept 15 2006, 38 evaluable pts (median age 56 years [range 29–78]; 2–3 metastatic sites [63%]; prior treatment with 5-FU ± platinum [P] [24%], capecitabine ± P [13%], TS-1 ± P [26%], other [37%]) have received a median of 2 SU cycles (range 1–3). Of 21 pts evaluable for efficacy, 1 PR has been confirmed and 8 pts had stable disease (SD), 4 with SD for =2 cycles. The most commonly reported AEs were typically grade 1/2 in severity and included stomatitis, skin discoloration, fatigue, anorexia, diarrhea, hand-foot syndrome (HFS), nausea and vomiting. Grade 3/4 toxicities included HFS (10.5%), fatigue (7.9%), anorexia (7.9%) and mucosal inflammation (5.3%). Grade 3/4 hematologic toxicities included neutropenia (29%), thrombocytopenia (29%) and anemia (11%). 7 pts experienced serious SU- related AEs requiring dose modifications in 3 pts and treatment discontinuation in 1 pt. Preliminary PK investigations indicate that concentrations seen in gastric pts are similar to those seen in other pts treated with SU. Conclusions: These initial findings show that SU is generally well tolerated and may have single-agent antitumor activity in pre-treated gastric cancer pts. Further trials with SU in combination with standard chemotherapy regimens are planned. No significant financial relationships to disclose.

A Multicentre Phase II Study of the Aminopeptidase Inhibitor, CHR- 2797, in the Treatment of Elderly and/or Previously Treated patients with Acute Myeloid Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 961-961 ◽  
Author(s):  
B. Lowenberg ◽  
F. Davies ◽  
C. Müller-Tidow ◽  
Ulrich Dührsen ◽  
A. Burnett ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Clinical Activity ◽  
Open Label ◽  
Elderly Aml ◽  
Previously Treated Patients ◽  
Previously Treated

Abstract Tosedostat (TSD, CHR-2797) is an aminopeptidase inhibitor that selectively depletes amino acid pools in malignant cells, resulting in anti-proliferative, pro-apoptotic and antiangiogenic effects. In a phase I study, treatment with TSD resulted in complete remission in a number of refractory AML patients. The primary objective of this phase II study was to determine whether TSD was a sufficiently effective therapy to warrant pivotal studies. Methods. This was an open label, single agent, phase II study to assess clinical activity of TSD in elderly and/or previously treated patients with AML/MDS. Patients were treated with once daily oral doses of the maximum acceptable dose (130 mg) of TSD for up to 84 days. Further treatment was allowed if, in the opinion of the investigator, this was considered to be beneficial. Clinical responses were assessed by monthly bone marrow aspirates and weekly hematological assessments. Results. Of the 41 TSD-treated patients with AML (n=38) or MDS (n=3), who were enrolled between March and October 2007, 27 were male, 14 female, with a mean age of 67 years (range 34–82). The median performance status (ECOG) at baseline was 1 (range 0–2). Twelve (31.6%) AML patients and 2 (66.7%) MDS patients were chemotherapy naïve, and 9 (23.7%) AML patients had either secondary disease or adverse cytogenetics. For 16 (39%) patients, treatment with TSD was a second or later salvage attempt. Thirty two patients (30 AML, 2 MDS-RAEB1 and 2) received ≥28 days treatment, and 21 (51.2%) patients completed the formal 84-day study period (19 AML, 2 MDS). Nine (22%) of the patients (7 AML, 2 MDS) continued treatment with TSD after 84 days, and 6 (15%) patients were on TSD in total for more than 6 months (4 AML, 2 MDS). Ten (26.3%) of the AML patients responded to treatment; amongst these, 2 patients received TSD as 2nd/3rd salvage therapy, and a further 2 patients did not show a complete response (CR) after 2 previous induction courses of chemotherapy. Three AML patients achieved a CR (< 5% blasts in bone marrow), of whom 2 were in durable remission (232 days, continuing*; 171 days), and 7 had a partial response (PR, 5–15% blasts) lasting approximately 1–3 months. Two (66.7%) of the MDS patients also responded to treatment with TSD; these patients maintained stable disease for more than 6 months. All responders (CR, PR and SD) were >60 years at the time of the first dose. Median overall survival in AML patients was 130 days (range 8 – 478 days*). The most frequently reported adverse events were: fatigue (61%), thrombocytopenia (49%), pyrexia (39%), peripheral edema (39%) and diarrhea (34%); 9 (22%) patients withdrew due to drug related toxicity. TSD had no effect on hemoglobin or neutrophils. Conclusions. This study in patients with advanced AML/MDS with adverse prognosis demonstrates the anti-leukemic activity of TSD in elderly AML patients, as measured by CR and decreases in leukemic blasts. In addition, 2 relapsed high risk MDS patients achieved disease stabilization. TSD at 130mg qd is also very well tolerated over a long period of exposure (6–10 months). These results support further pivotal studies with TSD in elderly AML and MDS patients.

Thalidomide in Advanced Mastocytosis. Results from an Open-Label, Multicentric, Phase II Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1754-1754
Author(s):  
Berengere Gruson ◽  
Olivier Lortholary ◽  
Danielle Canioni ◽  
marie-Olivia Chandesris ◽  
Fanny Lanternier ◽  
...  
Keyword(s):  
Mast Cell ◽  
Missing Data ◽  
Phase Ii ◽  
Conflicts Of Interest ◽  
Phase Ii Study ◽  
Single Agent ◽  
Open Label ◽  
Effective Response ◽  
Kit Mutation ◽  
Tryptase Level

Abstract Abstract 1754 Background: Mastocytosis is characterized by the abnormal accumulation of mast cells in various tissues responsible for organ failure and/or systemic symptoms that can be disabling and alter the quality of life (QOL). Beside symptomatic treatments, cytoreductive drugs such as a-interferon, purine analogs and to a less extent imatinib mesylate (in case of c-kit mutation other than D816V) and masatinib were shown to be effective but rare complete or long-term remissions were obtained. Thalidomide is an anti-angiogenic immuno-modulatory and anti-inflammatory drug that has preliminary been shown to have an activity in aggressive systemic mastocytosis (ASM) (Damaj et al, BJH 2008). We report the result of a multicentric, open-label, phase II study using thalidomide as a single agent in advanced SM (NCT00769587). Patients and Methods: Twenty patients (pts) were enrolled (1 missing data): smoldering systemic (SSM, n=9), ASM (n=6) and with an associated clonal hematologic non mast cell lineage disease (SM-AHNMD, n=4). Infiltrated organs were bone marrow (n=16), skin (n=14), splenomegaly (n=10), hepatomegaly (n=6), intestinal tract (n=6), lymph nodes (n=1). Median serum tryptase level at inclusion was 83.4 ng/L (range 5.3–775) and all patients except one carried the c-kit D816V mutation. Patients presented with anemia (n=6), thrombocytopenia (n=6) and neutropenia (n=1). Four patients were excluded, 1 for missing data and 3 were not evaluable. Thalidomide was administered orally at a starting dose of 50 mg/day and was progressively increased up to 200 mg/day or appearance of side effects. The duration of treatment was 6 months (1 cycle= 1 month). Responder patients may continue on thalidomide for a maximum of 12 months or progression. Primary objective was to determine the effective response rate by assessing the tumor burden. Secondary objectives were to assess the tolerance of thalidomide and to evaluate the QOL, depression (Hamilton score), pruritis, and handicap (Afirmm V2 score) related to mast cell disease. Results: Sixteen pts [7 males, 9 females; median age 65 years (range 43–76)] who received at least one cycle of thalidomide were analyzed. The median number of thalidomide cycles was 6 (range 1–20) and the median dose received was 100mg/d. Partial response was obtained in 9 pts (56%), 4 pts remained stable (25%) and 3 pts progressed (19%). Pruritis score decreased significantly from 6.5 (95% CI 4.74–12.26) to 4 (95% CI 0–5.25) (p=0.03); the Afirmm score tended to improve from 116.5 (95% CI 55.0–168.3) to 92.5 (95% CI 37.4–131.2) (p=0.38) with no improvement of QoL and Hamilton scores, median tryptase level or cytopenia. Skin infiltration disappeared only in 2 of 14 patients concerned. Treatment discontinuation was due to failure in 4 pts, side effect in 2 pts and patient's decision in 2. Thalidomide was continued in five pts as a maintenance therapy for a median duration of 6 mo (4–14). The most relevant toxicities (grade 3–4) consisted in peripheral neuropathy (12.5%) and myelosuppression (18.7%). Conclusions: Thalidomide is an acceptable and effective treatment in advanced SM. Disclosures: No relevant conflicts of interest to declare.

Phase II study of recombinant IL-21 (rIL-21) plus sorafenib as second- or third-line therapy for metastatic renal cell cancer (mRCC): Final results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3023-3023 ◽  
Author(s):  
S. Bhatia ◽  
E. Heath ◽  
I. Puzanov ◽  
W. Miller ◽  
B. Curti ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Cancer ◽  
Single Agent ◽  
Cell Activity ◽  
Unmet Need ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line ◽  
Line Setting

3023 Background: Despite the positive impact of targeted therapies on treatment for mRCC, the efficacy of these agents appears to decrease beyond the first-line setting. There is an unmet need for novel therapies after failure of vascular endothelial growth factor (VEGF)-directed agents. rIL-21, a cytokine that enhances CD8+ T-cell and NK cell activity, has single-agent antitumor activity (J Clin Oncol. 2008;26:2034). Based on promising results of a phase I study of rIL-21 plus sorafenib, we initiated a phase II study to explore the safety and efficacy of this combination as second- or third-line treatment for mRCC. Methods: Patients with mRCC received second- or third-line therapy with sorafenib 400 mg PO BID continuously plus rIL-21 30 μg/kg IV on days 1–5 and 15–19 of each 7-week treatment course (TC). Efficacy endpoints included progression-free survival (PFS) and overall response rate (ORR) per RECIST. Response was assessed by the investigator and by independent radiologic review (IRR). Results: 33 patients were enrolled from 14 sites in the U.S. and Canada. Median age was 61 years (range, 46–75); ECOG performance status was 0 (n=15) or 1 (n=18). Patients had received 1 (n=25) or 2 (n=8) prior lines of therapy, including sunitinib (n=19), temsirolimus (n=5), bevacizumab (n=3), everolimus (n=2), IL-2 (n=11), or other (n=4). Grade ≥3 adverse events considered at least possibly related to study drug and occurring in ≥3 patients included hypophosphatemia (33%), hand-foot syndrome (24%), rash (24%), thrombocytopenia (8%), and neutropenia (8%). Twelve patients remain on study; 13 withdrew for progressive disease (PD), 6 for toxicity, and 2 for other reasons. IRR has been performed for the first 23 patients who completed at least 1 full TC, with 6 confirmed PR (26%), 1 unconfirmed PR (4%), 14 SD (61%), and 2 PD (9%). While median PFS cannot yet be determined, 14 of the first 29 patients have completed at least 3 TCs, equivalent to approximately 21 weeks, with SD or better. Conclusions: rIL-21 plus sorafenib is associated with an acceptable safety profile and promising antitumor efficacy in previously treated patients with mRCC. The observed ORR to date compares favorably with the rate previously reported for sorafenib in the first and second-line setting. [Table: see text]

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