A phase II study of cabozantinib in patients (pts) with relapsed or refractory metastatic urothelial carcinoma (mUC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 307-307 ◽  
Author(s):  
Andrea Borghese Apolo ◽  
Howard L. Parnes ◽  
Ravi Amrit Madan ◽  
James L. Gulley ◽  
John Joseph Wright ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Primary Objective ◽  
Response To Therapy ◽  
Bone Lesions ◽  
Clinical Activity ◽  
Prior Therapy ◽  
Visceral Metastases ◽  
Carcinoma Of The Bladder ◽  
Grade 3

307 Background: Translational studies have shown that shed MET levels in serum and urine of pts with UC correlate with stage and visceral metastases and that cabozantinib reverses HGF-driven UC cell growth and invasion. These data support the evaluation of cabozantinib in pts with mUC. Methods: In this phase II study, pts receive cabozantinib 60 mg daily in 28-day cycles. There are 3 study cohorts (1) mUC, (2) bone only mUC (3) metastatic rare bladder histology. The primary objective is to determine the response rate (RR) by RECIST. Response is assessed every 2 cycles. Tissue, blood, and urine were collected on all pts to test for MET/HGF and immune subsets. Results: 26 out of 55 pts have enrolled (19 M, 7 F): median age 62 (42-82) and median KPS of 80%. Primary sites include bladder (77%) and upper tract UC (23%). Prior therapy includes 30% pts with 1 regimen, 39% with 2, 15% with 3, 8% with 4 and 8% with 6. 81% of pts had visceral metastases (lung, liver and bone) and 19% lymph node only metastases. 23 pts (19 in cohort 1, 3 in cohort 2 and 1 in cohort 3) were evaluable for response after completing at least 4 weeks of therapy. In cohort 1, 2 pts achieved PR (1 remained on study for 10 months and 1 remains on study after >12 months of therapy); 7 pts had SD for at least 16 weeks (1 remained on study for 11 months); 10 had PD; 1 is too early to assess for response; 1 was removed before restaging for toxicity and 1 was removed for not meeting eligibility. The objective RR is 11% and SD 37% for a clinical benefit of 48%. In cohort 2, 1 of 3 pts had a near resolution of bone lesions on NaF PET/CT for 11 months. In cohort 3, only pt enrolled (squamous cell carcinoma of the bladder) achieved SD for 16 weeks. Mixed responses with regression of lung, bone or lymph nodes were observed in 30% of pts with PD. Grade 3/4 toxicities included: fatigue (8%), hyponatremia (8%), hypophosphatemia (8%) diarrhea (4%), thromboembolism (4%), transaminitis (4%), hypothyroidism (4%), thrombocytopenia (4%), dysphonia (4%), hypomagnesemia (4%), creatinine increase (4%) and proteinuria (4%). Conclusions: Cabozantinib has clinical activity in pts with relapsed or refractory mUC with manageable toxicities. Further studies are underway to correlate response to therapy with MET expression. Clinical trial information: NCT01688999.

Phase II Study of Lenalidomide (CC-5013, Revlimid®) for Patients (pts) with Myelofibrosis (MF).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 377-377
Author(s):  
Jorge Cortes ◽  
Deborah Thomas ◽  
Srdan Verstovsek ◽  
Francis Giles ◽  
Miloslav Beran ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Myeloproliferative Disorders ◽  
Clinical Activity ◽  
Toxicity Profile ◽  
Prolonged Administration ◽  
Prior Therapy ◽  
Days Of Therapy ◽  
Grade 3 ◽  
Baseline Hemoglobin

Abstract Introduction: Thalidomide has been shown to induce responses in pts with MF but prolonged administration in these pts may be associated with neurotoxicity and other adverse events. Lenalidomide is the lead clinical compound in a new group of drugs called IMiDs®, which have immunomodulatory properties. It affects cytokine expression 200–5000 times more potently than thalidomide but lacks the teratogenecity, sedation and neurotoxicity. Methods: We thus designed a phase II study for pts with myelofibrosis (primary or associated with myeloproliferative disorders) with a platelet (plt) count of at least 30 x109/L. Pts may have received prior therapies, but were excluded if they had known hypersensitivity to thalidomide. Pts received lenalidomide 10 mg/day orally (5 mg daily for patients with platelet count less than 100,000 at study entry). Results: We have treated 41 pts. Their median age was 65 (range, 42 to 83). Thirty-six pts (88%) had received prior therapy for MF, including thalidomide 13 (32%), hydroxyurea 12 (29%), interferon 11 (27%) (pegylated 7), anagrelide 10 (24%), and erythropoietin 6 (15%). Baseline hemoglobin was <10g/dl in 19 (46%) (13, 32% transfusion dependent); platelets <100 x109/L in 12 (29%); neutrophils <1.5 x109/L in 2 (5%), and 20/34 (59%) had splenomegaly (median 10cm BCM, range 1 to 30) (7 prior splenectomy). Twenty pts are evaluable for response and toxicity (i.e., received at least 30 days of therapy, unless discontinued because of progression or toxicity). One pt discontinued therapy because of toxicity (grade 3 rash). Responses have been observed in 10 (50%) pts. These include CR in 2 pts (normalization of Hgb and WBC, respectively), PR in 2 pts (improvement in plts and hgb, ± spleen), hematologic improvement in 6 pts (improvement in plts 3, spleen 2, WBC 1). Three of 13 transfusion-dependent pts have become transfusion independent. The median time to response was 9 weeks (range, 2 to 22). Responses have been sustained for a median of 14 weeks (range, 2 to 28 weeks). Therapy has been well tolerated. The more common toxicities were rash in 12 (29%), and pruritus in 8 (20%). Grade ≥ 3 toxicities were thrombocytopenia (n=2), rash (n=1), fatigue (n=1), and neutropenia (n=1). Four (10%) pts have required dose reduction and 1 discontinued therapy because of toxicity (rash). Conclusion: We conclude that lenalidomide has clinical activity in a subset of patients with myelofibrosis with an acceptable toxicity profile. Studies using lenalidomide in combination with other agents are justified.

Phase II study of lenalidomide (CC-5013) for patients with myelofibrosis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6510-6510
Author(s):  
S. Verstovsek ◽  
J. Cortes ◽  
D. Thomas ◽  
M. Beran ◽  
C. Koller ◽  
...  
Keyword(s):  
Phase Ii ◽  
Total Bilirubin ◽  
Phase Ii Study ◽  
Performance Status ◽  
Clinical Activity ◽  
Prior Therapy ◽  
Grade 3 ◽  
Factor Α ◽  
Necrosis Factor ◽  
Baseline Hemoglobin

6510 Background: Lenalidomide (CC-5013, Revlimid), analogue of thalidomide, a new drug in a group known as ImiDs, with broad cytokine modulatory activity. Lenalidomide is less toxic than thalidomide without teratogenicity, sedation, or neurotoxicity, and is 50,000-fold more potent in inhibiting, tumor necrosis factor-α, that is involved in the pathophysiology of myelofibrosis (MF). Patients (pts) with MF currently have no approved standard effective therapy. Methods: Phase II study of lenalidomide for MF pts with plts >30×109, performance status ≥3, total bilirubin and creatinine of <3mg/dL, accrued 41 pts. Pts with prior hypersensitivity to thalidomide excluded. Pts received lenalidomide 10mg orally daily (5mg if platelets <100x109). Median age 65 (range, 42–83). 36 pts (88%) had received prior therapy for MF, including thalidomide 13 (32%), hydroxyurea 13 (32%), interferon 11 (27%), anagrelide 10 (24%), and erythropoietin 6 (15%). Baseline hemoglobin was <10g/dl in 19 (46%) (13 or 32% were transfusion dependent), platelets <100x109 in 12 (29%), absolute neutrophils <1.5x109 in 2 (5%), 20/34 (59%) had splenomegaly (median 10cm BCM, range 1–30; 7 with prior splenectomy), and 17 (42%) had cytogenetic abnormality. Results: Median follow is 5 months (range 1–14). Therapy has been well tolerated. Most common toxicities of any grade were rash 6(39%) and pruritus 9 (22%). Grade ≥3 toxicities were neutropenia 13 (32%), thrombocytopenia 11 (27%), fatigue 3 (7%) and rash 2 (5%). 8 (20%) pts required dose reduction; 4 discontinued therapy due to toxicity. Responses have been observed in 19 (46%) pts. These include CR 3(7%; normalization of hemoglobin and WBC), PR 5 (12%; improvement in platelets and hemoglobin ± spleen), and hematologic improvement 11 (27%) pts (improvement in platelets - 4, spleen - 2, WBC - 4, BM blasts - 1). 5 of 13 transfusion-dependent pts have become transfusion-independent. 6 of 12 (50%) pts with platelets <100x109 improved the count by >50%. Median time to response was 6 wks (range 1–22). Responses have been sustained for a median of 31+ wks (range 1+-40+). Conclusions: Lenalidomide has clinical activity in a subset of pts with MF with an acceptable toxicity profile. Studies using lenalidomide in combination with other agents are planned. No significant financial relationships to disclose.

Phase II Study of TRIplet combination Nivolumab (N) with Dabrafenib (D) and Trametinib (T) (TRIDeNT) in patients (pts) with PD-1 naïve or refractory BRAF-mutated metastatic melanoma (MM) with or without active brain metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9520-9520
Author(s):  
Elizabeth M. Burton ◽  
Rodabe Navroze Amaria ◽  
Isabella Claudia Glitza ◽  
Denai R. Milton ◽  
Adi Diab ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Unmet Need ◽  
Stage Iv ◽  
Primary Objective ◽  
Stopping Rules ◽  
Clinical Activity ◽  
Grade 3

9520 Background: Targeted therapies (TT) & immunotherapies (IMT) have improved survival for pts with BRAF V600 mutated stage IV MM, however many pts still progress and ultimately die from their disease. Preclinical data support the rationale for combining TT and IMT, but trials evaluating triplet combinations in IMT-naïve pts have reported mixed results. Notably, pts with untreated brain metastases (BM) were excluded from prior triplet trials and have a median PFS of 5.6 months when treated with TT. Further, there remains an unmet need for effective therapies for pts after IMT failure, as retrospective studies have reported short median PFS (5 mos) for TT in this setting. We hypothesized that N in combination with DT is safe and will demonstrate clinical activity in BRAF-mutated pts naïve or refractory to PD1 therapy and in pts with BM. Methods: We conducted a single arm phase II study (NCT02910700) of NDT in pts with BRAF-mutated, unresectable stg III or stg IV MM. Prior IMT was allowed, but prior BRAF/MEKi was not. Pts with untreated BM and asymptomatic or mildly symptomatic/requiring steroids were also allowed. Pts received 3mg/kg IV Q2wks of N (later amended to 480 mg IV Q4wks), 150mg PO BID of D and 2mg PO QD of T, all starting on Day 1. The primary objective was to determine safety and efficacy (ORR by RECIST 1.1). Monitoring for safety and futility using Bayesian stopping rules was performed. Longitudinal tissue and blood samples were collected to perform correlative analyses. Results: Following a 6 pt safety run-in with no observed DLTs, 27 pts were treated w NDT. 17 pts were PD1 refractory, 10 were PD-1 naïve. 10 of these 27 pts had a history or presence of BM, including active BM. Median follow up was 18.4 months (range 3.2-45.9). ORR in 26 evaluable pts was 92% (3 CR, 21 PR). Among the PD1 refractory pts evaluable for response (n = 16), ORR was 88% (2 CRs, 12 PR). All 10 evaluable PD-1 naïve pts achieved a response. 4 of 7 evaluable pts w BM achieved an intracranial response (57%), including 2 CRs. The median PFS for all pts was 8.5mos (8.5mos in PD1 naïve pts, 8.2mos in PD1 refractory pts). Median PFS for pts without BM was 8.5mos, 8.0 mos for those with BM. Median OS for all pts was not reached, and no statistically significantly difference in OS by PD1 exposure or presence of BM. 78% of pts experienced treatment related grade 3/4 AEs and 6 pts (22%) discontinued all 3 drugs due to toxicities. Conclusions: NDT at full doses of all 3 agents has a toxicity profile consistent with previously reported triplet combinations and shows promising clinical activity in pts with IMT refractory disease and with BM. There were no significant differences in outcomes between pts with and without BM. Translational studies to delineate predictors and mechanisms of response and resistance are ongoing. Clinical trial information: NCT02910700.

University of Chicago Consortium phase II study of ispinesib (SB-715992) in patients (pts) with advanced renal cell carcinoma (RCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15573-15573
Author(s):  
K. W. Beekman ◽  
R. Dunn ◽  
D. Colevas ◽  
N. Davis ◽  
J. Clark ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Primary Objective ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Elevated Alkaline Phosphatase ◽  
Multiple Tumor ◽  
Grade 3 ◽  
Metastatic Rcc

15573 Background: Ispinesib is a novel kinesin spindle protein inhibitor that has significant antitumor activity in multiple tumor models and has demonstrated preliminary clinical activity in early phase I and II trials. A phase II study of Ispenisib in patients with metastatic RCC who had received at least one prior therapy was thus conducted. Methods: The primary objective was to assess the RECIST based overall response rate (RR) with optimal Simon two-stage design utilizing 10% and 30% RR as the null and alternative hypotheses, respectively. Eighteen pts were to be accrued during the first stage; if 3 or more responses (PR or CR) were seen, an additional 17 pts would be accrued. Further study would be recommended if 7 or more of the 35 total pts had a response. Secondary objectives included toxicity, time to progression, and overall survival. Pts were treated with 7 mg/m2 over one hour on days 1, 8, and 15 every 28 days with radiologic disease re- evaluation every 8 weeks. Results: 19 pts were accrued in 6 months. Baseline characteristics included clear cell histology in 74%, papillary in 11%, and unclassified in 11%; 1 or =2 prior therapies in 37% and 63%; prior immunotherapy in 53%, and prior sunitinib, sorafenib or bevacizumab in 79%; ECOG performance status 0 in 58% and 1 in 42%. 4 patients are too early for radiologic assessment. None of the 15 patients evaluable responded to treatment (95% CI: 0 - 21.8%). Seven patients (47%) experienced stable disease after 8 weeks. One patient experienced grade 3 neutropenia. No other grade 3 or 4 toxicities were attributable to drug. Grade 1 and 2 toxicities included: fatigue (28%), anemia (28%), leukopenia (33%), elevated alkaline phosphatase (18%), anorexia (11%), hyponatremia (11%), dyspnea (11%), headache (11%), and hypoalbuminemia (11%). Conclusions: Treatment with weekly Ispenesib in metastatic RCC is well tolerated but does not lead to objective responses. Under the hypothesis that Ispenesib is a cytotoxic rather than cytostatic agent, further evaluation in patients with metastatic RCC at this dose and schedule is not indicated. Supported by: NCI #N01-CM-62201 No significant financial relationships to disclose.

A Phase II Study of Temsirolimus (CCI-779) in Patients with Advanced Leukemias.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4523-4523 ◽  
Author(s):  
Karen W.L. Yee ◽  
Guillermo Garcia-Manero ◽  
Deborah Thomas ◽  
Farhad Ravandi-Kashani ◽  
Srdan Verstovsek ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Blast Crisis ◽  
Single Agent ◽  
Mammalian Target Of Rapamycin ◽  
Median Number ◽  
Prior Therapy ◽  
Flat Dose ◽  
Grade 3

Abstract Temsirolimus (CCI-779, Wyeth Pharmaceuticals) has been shown to inhibit proliferation of a variety of tumors and induce G1 cell cycle arrest by preventing activation of the serine/threonine kinase, mTOR (mammalian target of rapamycin), a downstream effector of the PI3K/Akt pathway. Several lines of evidence implicate the PI3K/Akt/mTOR pathway in hematological malignancies. Interim results of a phase II study evaluating the efficacy and toxicity of single-agent temsirolimus in patients with advanced malignancies are presented. Temsirolimus was administered weekly, at a flat dose of 25 mg, as a 30-minute intravenous infusion. Treatment was continued until evidence of disease progression or unacceptable toxicity. To date, 8 patients have been enrolled and 7 are evaluable for efficacy and toxicity (one patient did not receive temsirolimus). Of these 7 patients, 5 had AML, 1 CML-myeloid blast crisis, and 1 ALL. Median age was 68 years (range, 21 to 87 years) and 5 were male. All patients had received prior therapy, median 2 regimens (range, 1 to 3 regimens). The median number of temsirolimus doses administered was 3 (range, 1 to 10) with a median time on study of 18 days (range, 3 to 89+ days). The most common temsirolimus-related adverse events were grade ≤ 2 and consisted of anorexia, nausea and/or vomiting and diarrhea, mucositis, dermatitis, hypertriglyceridemia, hyperglycemia, hypomagnesemia, hypocalcemia, hypokalemia, hypophosphatemia, and fatigue/asthenia. No patient developed nonspecific pneumonitis. Grade 3 toxicities included fatigue/asthenia (2), hyperglycemia (1), painful mucositis with dehydration and electrolyte abnormalities (1), diarrhea with hypokalemia (1), and hypophosphatemia (1). No patient experienced grade 4 toxicities or death from temsirolimus. No patient required dose reductions, but 2 did have dose delays due to grade 3 mucositis (1) and out-of-state hospitalization for pneumonia and atrial fibrillation (1). No patient achieved a complete remission. One patient with heavily pre-treated Philadelphia-negative precursor B-cell ALL had a transient 79% to 91% reduction in peripheral blood blasts 4 days after the first dose of temsirolimus that was maintained for 12 days prior to disease progression with involvement of the synovial fluid in bilateral knees. At the time of analysis, 6 of the 7 patients have discontinued treatment due to disease progression (4), patient refusal (1), or physician decision (1). Preliminary findings indicate that temsirolimus is relatively well-tolerated at a dose of 25 mg per week and may have biologic activity in ALL. Accrual onto the study is currently ongoing.

Phase II study of AZD2171 for the treatment of patients with myelodysplastic syndromes.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6570-6570
Author(s):  
Shannon Eileen O'Mahar ◽  
Alcee Jumonville ◽  
Patrick J. Flynn ◽  
Alvaro Moreno-Aspitia ◽  
Charles Erlichman ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Prior Therapy ◽  
Starting Dose ◽  
Orally Bioavailable ◽  
Grade 3 ◽  
Endothelial Growth Factor

6570 Background: Inhibition of vascular endothelial growth factor receptors (VEGFR) can block growth and trigger apoptosis in neoplastic cells. AZD2171 (cediranib) is a highly potent, orally bioavailable, VEGFR-1/2 inhibitor. We conducted a phase II study of the efficacy of AZD2171 for the treatment of MDS. Methods: Adults with MDS (IPSS Int-2 or High) were eligible if they exhibited adequate organ function and ECOG 0-2. The primary endpoint was proportion of responses according to the IWG criteria assessed at one and every 3 months. Prior investigation of cediranib at 45 mg daily in patients with acute leukemia demonstrated toxicity concerns and therefore, the starting dose of this study was lowered to 30 mg daily. Results: A total of 16 pts with MDS (median age 73 years) were enrolled at a 30 mg starting dose, and all were evaluable. Median baseline marrow blasts were 12.0 % (range 2-18); 3 pts (18.8 %) had low, 6 (37.5 %) intermediate, and 7 (43.8 %) had high risk cytogenetics. Prior therapy included azacitidine (n=7), decitabine (n=2), cytarabine (n=2), erythropoietin-stimulating agents (ESAs) (n=2), lenalidomide (n=1), or none (n=6). Patients were treated for a median of two 28-day cycles (range 1 to 11). There were no confirmed responses. Patients with baseline blasts > 5% showed no significant reduction in the blast count at 4 and 12 weeks. Median OS was 4.7 mo (95% CI: 2.6 – 11.6). Median TTP was 3.8 mo (95% CI: 1.7 – 10.8). Grade 4 hematological adverse events at least possibly related to cediranib were neutropenia (n=2) and thrombocytopenia (n=4). Grade 3 hematological adverse events at least possibly related to study treatment included: neutropenia (n=3), thrombocytopenia (n=2), and anemia (n=2). Grade 3 non-hematological adverse events included fatigue (n=4), dyspnea (n=3), dehydration (n=2), diarrhea (n=2), nausea (n=2), asthenia (n=1), and hypertension (n=1). Hypertension and proteinuria was uncommon with the 30 mg/day dose. Conclusions: With no confirmed response from 16 patients, cediranib was determined to be ineffective at a dose of 30 mg daily in our patient population. Supported by NCI N01-CM62205, NCI P30-CA014520 and the UW Carbone Comprehensive Cancer Center.

An open-label international multicentric phase II study of nilotinib in progressive pigmented villo-nodular synovitis (PVNS) not amenable to a conservative surgical treatment.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10516-10516 ◽  
Author(s):  
Hans Gelderblom ◽  
David Pérol ◽  
Christine Chevreau ◽  
Martin HN Tattersall ◽  
Silvia Stacchiotti ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Primary Tumour ◽  
Disease Stabilisation ◽  
Primary Objective ◽  
Neoplastic Disease ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Maximum Sample Size ◽  
Grade 3

10516 Background: PVNS, also known as tenosynovial giant cell tumor (TGCT), is a rare pathological entity affecting the synovium in young adults. This neoplastic disease is driven by a t(1;2) translocation resulting in the fusion of COL6A3 and M-CSF genes. Nilotinib has inhibitory properties on M-CSF receptor pathway which could be of therapeutic interest in patient (pts) with non resectable PVNS. Methods: In this open-label international, multicentric, non-randomized, phase II study the primary objective is to evaluate the efficacy of nilotinib treatment (800 mg/day) in pts with progressive or relapsing PVNS not amenable to surgery or in whom surgery would be mutilating, as measured by the 12-week progression-free rate (12-w PFR) validated by an independent committee. Using a Bayesian design with a futility stopping rule and a maximum sample size set to 50 evaluable pts, interim analyses (IA) were planned after the inclusion of 10 and then every 5 pts. Results: From December 2010 to September 2012, 56 pts with progressive disease were enrolled by 17 institutions from Europe and Australia. Successive previous IA led to positive results in favour of the study continuation. 47 pts (median age 37 y (range: 18-74), 51% of males) were evaluable at the time of the last IA, with a median follow-up of 11.2 months (range: 0.6-12.7). Median time since diagnosis was 2.5 years (range: 0.02-26). Primary tumour was mainly located on knee (25 pts, 53%), hip (6 pts, 13%), ankle (6 pts, 13%). 4 pts had already received imatinib, 76% of pts had undergone a previous surgery. The 12-w PFR was 93.6% (95%CI, 82.5%-98.7%), without any OR. PR were observed later (2 at w-24 and 1 at w-48). Nilotinib was well tolerated, with only 4 pts experiencing grade 3 adverse events (anorexia: 1 pt; prurit: 1 pt; diarrhea: 1 pt; hepatic failure: 1 pt). 8 pts (17%) had a dose reduction and/or temporary discontinuation of nilotinib due to toxicity. Final results will be further presented. Conclusions: Nilotinib treatment induces disease stabilisation in a large proportion of PVNS patients with non resectable disease or in whom resection would be mutilating. Clinical trial information: NCT01261429.

RECIST and iRECIST criteria for the evaluation of nivolumab + ipilimumab combination in patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC): Results of the GERCOR NIPICOL phase II study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 101-101 ◽  
Author(s):  
Romain Cohen ◽  
Jaafar Bennouna ◽  
Julie Henriques ◽  
Christophe Tournigand ◽  
Christelle De La Fouchardiere ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Low Frequency ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3 ◽  
Clinical Trial Information

101 Background: Immune checkpoint inhibitors (ICKi) are highly effective for MSI/dMMR mCRC pts. RECIST1.1 criteria are reported to underestimate response to ICKi. The GERCOR NIPICOL phase II study aimed to evaluate disease control rate (DCR) using RECIST1.1 and iRECIST for MSI/dMMR mCRC pts treated with nivolumab (NIVO) and ipilimumab (IPI). Methods: MSI/dMMR mCRC pts previously treated with fluoropyrimidines (FP), oxaliplatin (OX) and irinotecan (IRI) ± targeted therapies received NIVO 3 mg/kg + IPI 1 mg/kg Q3W for 4 cycles then NIVO 3 mg/kg Q2W until progression or a maximum of 20 cycles. CT-scan tumor assessments were done every 6 weeks during 24 weeks and then every 12 weeks. Primary objective was DCR at 12 weeks (12wDCR) according to RECIST1.1 and iRECIST by central review. Response rates and progression-free survival (PFS) by central review were secondary objectives. A one-stage Fleming design was used with a targeted improvement of 12wDCR from 70% to 85%. Results: Of 57 pts included between Dec 2017 and Nov 2018, 43.9% had received ≥ 3 prior lines including FP (100%), OX (100%), IRI (95.5%), antiangiogenics (57.9%) and anti-EGFRs (45.6%). 17.5% of pts had BRAF mutation and 27.5% Lynch syndrome. Grade 3-4 treatment-related adverse events were reported in 49.1% of pts, mainly hepatitis (12.3%). 12wDCR was 86.0% and 87.7% using RECIST1.1 and iRECIST respectively, with only 1 pseudo-progression (1.8%) observed during the first 12 weeks, and one later. Kappa coefficient between RECIST and iRECIST 12wDCR was 0.92 (95%CI 0.77-1.0). Best observed responses with RECIST1.1/iRECIST were: 2/2 complete responses (3.5/3.5%), 19/19 partial responses (33.3/33.3%), 30/31 stable diseases (52.6/54.4%) and 3/2 disease progressions (5.3/3.5%), with 3 pts not evaluable (cancer-related deaths before first evaluation). Conclusions: Combination of NIVO and IPI in MSI/dMMR mCRC is associated with a low frequency of pseudo-progression and high DCR rate. PFS will be evaluated in Dec 2019, with all pts having completed the predefined 1-year of ICKi therapy. Clinical trial information: NCT033501260.

Final efficacy results of NCIC CTG IND.202: A randomized phase II study of recombinant interleukin-21 (rIL21) in patients with recurrent or metastatic melanoma (MM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9032-9032 ◽  
Author(s):  
Teresa M. Petrella ◽  
Catalin Liviu Dragos Mihalcioiu ◽  
Elaine McWhirter ◽  
Karl Belanger ◽  
Kerry J. Savage ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Lesion Size ◽  
Primary Objective ◽  
Effector Memory ◽  
Prior Therapy ◽  
Randomized Phase Ii ◽  
Elevated Liver Enzymes ◽  
Biomarker Analysis

9032 Background: rIL21 is a T-cell derived cytokine with antitumor activity dependent on NK cells or CD8+ T cells through induction of central and effector memory cells. A previous phase II study demonstrated an ORR of 22.5% in previously untreated patients with MM. We conducted a multicentre randomized phase II study of MM evaluating the efficacy, toxicity, pharmacokinetics, immunogenicity, and biomarkers of rIL21 versus dacarbazine (DTIC). Methods: Eligible patients: Recurrent or MM, with either maximum tumour lesion size of < 50 mm or LDH < 2.5 x ULN and prior therapy with BRAF/MEK inhibitors allowed. Patients were treated with either rIL-21, 30 µg /kg/day dose IV daily x 5 days weeks 1, 3, 5 q 8 weeks or dacarbazine (DTIC) 1000 mg/m2 IV q 3 weeks. The primary objective was to compare progression free survival (PFS). The trial was designed to detect a hazard ratio of 1.75 with one-sided alpha of 0.1; 58 progression events were required to provide 80% power. Results: 64 patients were randomized, 32 in the rIL-21 arm and 32 in the DTIC arm. The Table summarizes key demographic and efficacy endpoints. Common rIl21 related adverse events were fatigue, rash, diarrhea, nausea, myalgia and elevated liver enzymes. At least one dose reduction/ interruption or discontinuation occurred in 32 (100%) and 27 (96.4%) of rIL21 and DTIC patients. Conclusions: Despite encouraging efficacy in prior phase I/II studies, the results suggest that rIL-21 is comparable to DTIC in this patient population. Additional biomarker analysis from this study is pending and combination studies are currently ongoing. Clinical trial information: NCT00514085. [Table: see text]

A phase 1b/2 study of INCB039110 + nab-paclitaxel (N) and gemcitabine (G) in patients (pts) with advanced solid tumors and pancreatic cancer (PC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 362-362 ◽  
Author(s):  
Gregory Lawrence Beatty ◽  
Safi Shahda ◽  
J. Thaddeus Beck ◽  
Nikhil Premparkash Uppal ◽  
Steven J. Cohen ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Cancer Progression ◽  
Malignant Cell ◽  
Primary Objective ◽  
Clinical Activity ◽  
Induction Phase ◽  
Open Label ◽  
Prior Therapy ◽  
Phase 1B ◽  
Grade 3

362 Background: JAK-STAT activity has been associated with malignant cell proliferation and production of proinflammatory cytokines involved in cancer progression. INCB039110 is a potent and selective inhibitor of JAK1. Methods: This was a 2-part phase 1b/2 open-label study evaluating INCB039110 (300 or 400 mg QD) in combination with N and G in pts with advanced or metastatic solid tumors (Part 1 [P1], dose optimization phase) and pts with advanced or metastatic PC who had not received prior chemotherapy (Part 2 [P2] and 2A [P2A]). Pts in P2 received the MTD established in P1: INCB039110 (300 mg QD) + N (125 mg/m2 day [d] 1, 8, 15) + G (1000 mg/m2 d 1, 8, 15), 28-d cycle. For exploratory purposes, pts in P2A underwent a 7-d induction phase with INCB039110 (200 mg QD) before receiving INCB039110 (200 mg QD) + N (125 mg/m2 d 1, 8, 15) + G (1000 mg/m2d 1, 8, 15). The primary objective was to evaluate safety/tolerability. Results: 55 pts were enrolled (27 P1, 20 P2, and 8 P2A). Most patients had advanced PC (n = 46). Median age was 65 (P1), 67 (P2), and 66 years (P2A). Prior therapy: 67% in P1, 30% in P2, and 0% in P2A. The most common reasons for treatment discontinuation were adverse events (AEs; 41% P1, 20% P2, 38% P2A), disease progression (37% P1, 45% P2, 0% P2A), and study termination by the sponsor (0% P1, 0% P2, 38% P2A). Median treatment durations were 84 d (P1), 121 d (P2), and 47 d (P2A). The most common non-hematologic AEs (all grades) were fatigue (59% P1, 75% P2, 88% P2A), nausea (41% P1, 50% P2, 38% P2A), pyrexia (37% P1, 40% P2, 13% P2A), and peripheral edema (30% P1, 50% P2, 25% P2A), with few grade 3 or 4 non-hematologic AEs. The most common grade 3 or 4 hematologic AEs (laboratory values) were neutropenia (33% P1, 60% P2, 13% P2A), lymphopenia (30% P1, 30% P2, 13% P2A), and leukopenia (30% P1, 45% P2, 0% P2A). The most common serious AEs occurring in ≥ 3 pts were pneumonia (n = 4 P1, n = 2 P2, n = 0 P2A) and anemia (n = 3 P1, n = 2 P2, n = 2 P2A). Among evaluable patients, ORR (all PRs) and DCR were 27% (13/48) and 75% (36/48), respectively. Responses were seen across INCB039110 doses. Conclusions: INCB039110 + N/G showed an acceptable safety profile in pts with advanced PC, with the combination demonstrating clinical activity. Clinical trial information: NCT01858883.

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