Regorafenib (R) in advanced solitary fibrous tumor (SFT): Results from an exploratory phase II clinical study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11558-11558
Author(s):  
Silvia Stacchiotti ◽  
Giacomo Giulio Baldi ◽  
Salvatore Lo Vullo ◽  
Carlo Morosi ◽  
Francesca Gabriella Greco ◽  
...  
Keyword(s):  
Response Rate ◽  
Alternative Hypothesis ◽  
Progression Free Survival ◽  
Error Rates ◽  
Cytotoxic Agents ◽  
High Rate ◽  
Antiangiogenic Agents ◽  
Type I ◽  
Phase 2 ◽  
Phase 2 Trial

11558 Background: R showed antitumor activity in a PDX model of dedifferentiated SFT (D-SFT), inducing a superior tumour growth inhibition than with other antiangiogenic agents (A), such as pazopanib (P) and axitinib (A). The efficacy of P and A in patients (pts) with advanced typical- (T-)/ malignant- (M-)SFT has been already confirmed in phase 2 clinical trials, but not in D-SFT. An exploratory phase 2 study was designed to investigate the activity of R in advanced SFT. Methods: An investigator-initiated exploratory phase 2 trial was started in December 2015 at the Istituto Nazionale Tumori, Milan, Italy, to evaluate the activity of R, 160 mg OD, 3 weeks on/1 week off, until progression or limiting toxicity. in > 18 years old pts with advanced SFT. The target sample size was 16 evaluable pts; at least 3 responses were requested to reject the null hypothesis of 5% in favour of an alternative hypothesis of 30% (with type-I and type-II error rates fixed at the 10% level). Eligible pts had to have evidence of progression. Prior treatment with A was allowed. Centralized pathologic review was performed, distinguishing T-SFT, M-SFT and D-SFT subtypes. The primary end-point was the overall response rate (ORR) by Choi. Secondary end-points were ORR by RECIST, progression-free survival (PFS), overall survival (OS). Results: Enrolment was completed in February 2021. Eighteen pts were enrolled (D-SFT = 4; M-SFT = 13; T-SFT = 1). Four pts were naïve, 14 were pre-treated [12 with antiangiogenics (4 with > 1 prior antiangiogenic line); 11 with cytotoxic agents]. Three pts are ongoing, 13 completed their treatment (11 = progression, 1 = toxicity, 1 = other). Fourteen pts are evaluable for response by Choi and RECIST (1 = screening failure; 1 = early discontinuation for toxicity before radiologic assessment; 2 = too early). A definitive dose reduction was required in 5 of 14 evaluable (35.7%) pts. The ORR by Choi was 42.9% (exact binomial 95% Confidence Interval [CI]: 17.7%-71.1%), with 6/14 (42.9%) partial responses (PR), 5/14 (35.7%) stable disease (SD) and 3/14 (21.4%) progressions (PD). Best responses by RECIST were: 1/14 (7.1%) PR, 10/14 (71.4%) SD, 3/14 (21.4%) PD. 5/6 pts responsive by Choi were pre-treated with another antiangiogenic. No responses were seen in the 3 D-SFT pts. At a m-FU of 23 months, m-PFS by Choi was 3.68 (IQR: 2.73-8.54) months, with 23.4% pts progression free at 1 year. m-PFS by Choi in responsive pts was 5.62 (IQR: 2.89 – 8.54) mos. Median OS was 15.7 (IQR: 7.35-not reached) months. Conclusions: R did not show a higher activity in D-SFT compared to P and A. The response rate was in the range observed with other A, but m-PFS was shorter. This may be due to discrepancies in pt populations and a high-rate of dose reductions with R. However, responses to R were seen also in pts previously treated with other A and almost one fourth of pts benefited from R for more than a year. Clinical trial information: 2015-002629-21.

Eribulin and gemcitabine in previously treated patients with advanced liposarcoma or leiomyosarcoma: A multicenter, single-arm, phase 2-trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11516-11516
Author(s):  
Chang Gon Kim ◽  
Jin-Hee Ahn ◽  
Jeong Eun Kim ◽  
Jee Hung Kim ◽  
Min Kyung Jeon ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Alternative Hypothesis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Histologic Types

11516 Background: Eribulin and gemcitabine have shown encouraging efficacy in soft-tissue sarcoma (STS) as a monotherapy. Here, we evaluated the activity and safety of combined use of eribulin and gemcitabine in two most common histologic types of STS, liposarcoma and leiomyosarcoma. Methods: In this non-randomized, multi-center phase 2 study, patients were included if they had progressive disease after one or two prior chemotherapy including doxorubicin. Patient were given eribulin 1.4 mg/m2 and gemcitabine 1,000 mg/m2 on day1 and day 8 every 3 weeks. The primary endpoint was progression-free survival rate at 12 weeks (PFSR12wks) with null and alternative hypothesis of PFSR12wks≤20.0% and ≥40.0%, respectively. Results: Of 37 patients included, 22 had leiomyosarcoma, and 15 had liposarcoma. At 12-weeks after treatment, 16 and (72.7%) 11 (73.3%) patients in leiomyosarcoma and liposarcoma were progression-free. Overall PFSR12wks was 73.0%, satisfying the primary endpoint. Objective response rate, disease control rate, median progression-free survival, and median overall survival were 16.2%, 78.4%, 23.9 weeks, and 88.9 weeks, without any statistical differences according to histologic subtypes. No new safety signals and treatment-related death were observed. Conclusions: Eribulin and gemcitabine showed promising activity and manageable safety profile in patients with STS of liposarcoma and leiomyosarcoma histology. Updated outcomes for ongoing patients will be presented. Clinical trial information: NCT03810976.

Randomized, double-blind, placebo-controlled, phase II trial of first-line platinum/docetaxel with or without erlotinib (E) in patients (pts) with recurrent and/or metastatic (R/M) head and neck squamous cell carcinomas (HNSCCs).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6017-6017 ◽  
Author(s):  
William Nassib William ◽  
Lei Feng ◽  
Merrill S. Kies ◽  
Salmaan Ahmed ◽  
George R. Blumenschein ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Type I Error ◽  
Performance Status ◽  
Local Treatment ◽  
Progression Free Survival ◽  
Type I ◽  
Phase 2 ◽  
First Line ◽  
Double Blind ◽  
Phase 2 Trial

6017 Background: In a single-arm, phase 2 study, we previously demonstrated that in pts with R/M HNSCC, cisplatin, docetaxel and E improved progression-free survival (PFS) compared to historical data (Kim et al., ASCO 2006). Herein, we evaluated this regimen in a single center, randomized, phase 2 trial. Methods: Pts with R/M HNSCC, with a performance status (PS) 0-2, were randomized (1:1) to receive up to 6 cycles of first-line chemotherapy with cisplatin 75 mg/m2 (or carboplatin AUC 6) and docetaxel 75 mg/m2 i.v. on day 1 every 21 days, plus placebo (P) vs. E 150 mg p.o. daily, followed by maintenance P or E until disease progression. The primary endpoint was PFS. With 120 pts, the study had 80% power to detect an improvement in median PFS from 3.0 to 4.9 months with a two-sided type I error rate of 0.1. Results: From 05/2010 to 07/2015, 120 pts were randomized to the P (N = 60) or E (N = 60) groups. All pts but one initiated treatment and were eligible for evaluation of the primary endpoint – 92 males; median age 62 years; 52 oropharynx, 40 oral cavity, 19 larynx, 8 hypopharynx cancer pts; 86 current/former smokers; 43 with recurrence within 6 months of completion of local treatment; 27 with prior exposure to EGFR inhibitors. Median PFS was 4.4 vs. 6.1 months for the P and E groups, respectively (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.42-0.95 months, p = 0.026). Response rates were 44% vs. 56% for P vs. E (p = 0.21). Median overall survival (OS) for P- and E-treated pts was 13.7 vs. 17.0 months (HR = 0.67, 95% CI 0.43-1.04, p = 0.07). Benefits from E on PFS and OS were more pronounced in pts with oropharyngeal tumors (p≤0.05 for interaction). In the E group, first-cycle rash grade 2-4 (34% pts) was associated with longer OS (HR = 0.40, p = 0.02). E-treated pts experienced a higher incidence of grade 3-4 adverse events (33.9 vs. 53.3%), including diarrhea (3 vs.17%), dehydration (5 vs. 15%), nausea (5 vs. 14%), rash (0 vs. 12%). Conclusions: This study met its primary endpoint. Addition of E to first-line platinum/docetaxel improved PFS and OS. This regimen may warrant further evaluation in randomized, phase 3 trials. Clinical trial information: NCT01064479.

scholarly journals Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil With Bevacizumab in Patients With Metastatic Gastroesophageal Adenocarcinoma

2011 ◽  
Vol 29 (7) ◽  
pp. 868-874 ◽  
Author(s):  
Manish A. Shah ◽  
Minaxi Jhawer ◽  
David H. Ilson ◽  
Robert A. Lefkowitz ◽  
Edric Robinson ◽  
...  
Keyword(s):  
Response Rate ◽  
Gastroesophageal Junction ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Error Rates ◽  
Diffuse Gastric Cancer ◽  
Type I ◽  
Patients With Cancer ◽  
Gastroesophageal Adenocarcinoma ◽  
Grade 3

Purpose To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF) with bevacizumab in patients with advanced gastroesophageal malignancies. Patients and Methods Previously untreated patients with metastatic gastroesophageal adenocarcinoma received bevacizumab 10 mg/kg, docetaxel 40 mg/m2, fluorouracil 400 mg/m2, leucovorin 400 mg/m2 on day 1, fluorouracil 1,000 mg/m2/d × 2 days intravenous continuous infusion beginning on day 1, and cisplatin 40 mg/m2 on day 3. The primary objective was to improve 6-month progression-free survival (PFS) from 43% (historical DCF control) to 63% with the addition of bevacizumab. The target accrual was 44 patients to have 10% type I and II error rates. Results In total, 44 eligible patients with cancer were enrolled from October 2006 to October 2008: 22 gastric, 20 gastroesophageal junction (GEJ), and two esophagus. In 39 patients with measurable disease, the confirmed response rate was 67% (95% CI, 50% to 81%). Six-month PFS was 79% (95% CI, 63% to 88%), and median PFS was 12 months (95% CI, 8.8 to 18.2 months). With 26-month follow-up, median overall survival (OS) was 16.8 months (95% CI, 12.1 to 26.1 months), and 2-year survival was 37%. Treatment-related grade 3 to 4 toxicity was as follows: neutropenia without fever (50%), fatigue (25%), venous thromboembolism (39%), and nausea, vomiting, mucositis, neuropathy, and febrile neutropenia less than 10% each. In subset analysis, diffuse gastric cancer had significantly worse PFS and OS, and the response rate in proximal/GEJ tumors was 85% (95% CI, 62% to 97%). Conclusion mDCF with bevacizumab appears tolerable and has notable patient outcomes in patients with advanced gastroesophageal adenocarcinoma. Six-month PFS was 79%, surpassing our predefined efficacy end point, and median and 2-year OS were 16.8 months and 37%, respectively.

AHOD0321: A COG Phase 2 Study of Weekly Gemcitabine and Vinorelbine for Children with Recurrent or Refractory Hodgkin Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2318-2318
Author(s):  
Peter D. Cole ◽  
Tanya M. Trippett ◽  
Richard A. Drachtman ◽  
Pedro de Alarcon ◽  
Lu Chen ◽  
...  
Keyword(s):  
Response Rate ◽  
Alternative Hypothesis ◽  
Single Agent ◽  
Hodgkin Disease ◽  
Hematologic Toxicity ◽  
Type I ◽  
Phase 2 ◽  
Response Data ◽  
Phase 2 Study ◽  
Grade 3

Abstract Introduction: This COG Phase 2 study was conducted to assess the efficacy and toxicity of gemcitabine and vinorelbine (GV) in pediatric patients with heavily pre-treated relapsed/refractory Hodgkin disease. Both agents have significant single-agent response rates in this setting, and preclinical data suggest the combination will be at least additive. Methods: GV was given on days 1 and 8 of each 21d treatment cycle: vinorelbine 25 mg/m2/dose IV push and gemcitabine 1000 mg/m2/dose IV over 100 minutes. Filgrastim 5 mg/kg/dose was started on Day 9 and continued for a minimum of 7 days, until the post-nadir absolute neutrophil count was greater than 1500/μL. Response was evaluated after every two cycles. Patients with measurable responses after two cycles were given the option of going off protocol therapy for stem cell transplantation (SCT). A minimum of two additional cycles was mandated for those with stable disease after two cycles. The statistical analysis of response used a two-stage minimax rule to test the null hypothesis that the response rate is ≤40% with 5% Type I error against an alternative hypothesis of a response rate >65%, with 80% power. Results: Thirty-one eligible patients with a median age of 17.8 years (range 10.7 – 29) were enrolled. Fourteen were female (45%). All patients had received at least 2 prior chemotherapy regimens and 17 had prior autologous SCT. Toxicity and response data are currently available for 24 patients who completed at least two cycles and 16 who completed four cycles of GV. Among those who completed two cycles, hematologic toxicity was predominant, including grade 3–4 anemia (50%), leukopenia (71%), neutropenia (79%), and thrombocytopenia (83%). Nonhematologic grade 3–4 toxicity included elevated SGPT (38%) or SGOT (21%) and hyperbilirubinemia (4%). No patients developed non-cardiogenic pulmonary edema. There have been three documented infectious complications, including febrile neutropenia, sinusitis, and a urinary tract infection. One patient, with a history of prior mediastinal irradiation, developed pericardial and pleural effusions following cycles 4 and 5 of GV, consistent with gemcitabine-induced radiation recall. There were no toxic deaths. Response data are available for 24 patients of whom 18 (75%) have had measurable responses: 5 CRs, 10 VGPRs, and 3 PRs. All radiographic evaluations of treatment response are undergoing centralized review and full response data for all enrolled patients will be available for presentation. Conclusion: GV is an effective and well-tolerated re-induction regimen for children with relapsed or refractory Hodgkin disease.

Erlotinib and bevacizumab in chemotherapy-naive performance status 2 patients with advanced non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19082-e19082
Author(s):  
T. Al Baghdadi ◽  
N. Hanna ◽  
S. Bhatia ◽  
J. McClean ◽  
C. Johnson ◽  
...  
Keyword(s):  
Alternative Hypothesis ◽  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Patient Characteristics ◽  
Poor Performance Status ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Patient Reported

e19082 Background: Poor performance status is a negative prognostic variable for survival and a risk for increased toxicities with standard chemotherapy. A phase 2 study combining erlotinib (E) and bevacizumab (B) demonstrated encouraging efficacy in the treatment of recurrent NSCLC with acceptable toxicity. We, therefore, tested this regimen in untreated PS 2 patients with advanced NSCLC. Methods: Single-arm phase 2 trial in treatment-naïve patients with advanced non-squamous NSCLC and either a PS of 2 or age >75. Only patients eligible for bevacizumab per label were allowed onto study. Patients received E 150 mg orally daily and B 15 mg/kg IV on day 1 every 21 days for up to 6 cycles. The primary end-point was the rate of non progressive disease at 4 months (alternative hypothesis P>60%). Other end-points included overall survival, progression free survival (PFS), toxicity evaluations and patient-reported PS (PRPS) measures. Results: 25 patients were enrolled. Patient characteristics: 56% female, median age 77 years (range: 52–90); 88% stage IV; 92% were PS 2; 20% were never or remote smokers (> 30 years) The PRPS was 1, 2, 3 in 32%, 52%, 8% respectively with data on 2 patients missing. The rate of non-progression at 4 months was 40%; overall best response: 5% PR, 40% SD, 50% PD and 5% unevaluable; median PFS 2.6 months, 95% CI (1.3–5.1); MST 5.8 months, 95% CI (3.8- 8.7). 2 patients had G3 rash. G3 diarrhea, G3 hemorrhage, G3 proteinuria, G3 duodenal ulcer and G3 pneumonitis each developed in one patient. Conclusions: E + B is an active regimen with an acceptable toxicity profile; however, this study did not meet its’ primary endpoint. Further study of this combination will not be pursued in the Hoosier Oncology Group for this patient population. [Table: see text]

scholarly journals CTNI-18. FINAL RESULTS OF A PHASE 2 STUDY OF EFFICACY, SAFETY AND INTRATUMORAL PHARMACOKINETICS (PK) OF SELINEXOR MONOTHERAPY IN RECURRENT GLIOBLASTOMA (rGBM)

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii46-ii46
Author(s):  
Andrew Lassman ◽  
Patrick Wen ◽  
Martin van den Bent ◽  
Scott Plotkin ◽  
Annemiek Walenkamp ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Median Number ◽  
Recurrent Glioblastoma ◽  
Phase 2 ◽  
Nuclear Retention ◽  
Phase 2 Trial ◽  
Human Gbm

Abstract BACKGROUND Selinexor is an FDA-approved first-in-class, oral selective nuclear export inhibitor which forces nuclear retention of many tumor suppressor proteins. METHODS We conducted a phase 2 trial of selinexor monotherapy for adults with recurrent GBM including a surgical arm to explore intratumoral PK and 3 medical arms to optimize dosing. Prior treatment with radiotherapy and temozolomide was required; prior bevacizumab was exclusionary. The primary endpoint was 6-month progression-free survival (6mPFS) rate. RESULTS Selinexor administered ~2 hours pre-operatively yieleded average intratumoral concentration (136 nM, n=6) comparable to the in vitro IC50 (130 nM) from 7 primary human GBM cell lines. Among all 68 patients accrued to 3 medical arms (~85 mg BIW, n=24; 60 mg BIW, n=14; 80 mg QW, n=30), median age was 56 years (21–78). Median number of prior lines of therapies was 2 (1–7). At 80 mg QW, 28% patients were progression-free at the end of cycle 6; the 6mPFS was 17%; disese control rate by RANO was 37% (1 CR, 2 PRs, 7 SD) among 27 evaluable patients; responses were durable (median 11.1 months), and treatment lasted for 442, 547 and 1282 days in 3 responders, as of data lock, with one responder remaining on treatment off study; median overall survival was 10.2 months with 95% CI (7.0, 15.4). The ~85 mg BIW-schedule was abandoned due to poor tolerability. The related adverse events (all grades) in patients on ~85 mg BIW/60 mg BIW/80 mg QW were nausea (41.7%/64.3%/66.7%), fatigue (70.8%/71.4%/50.0%), neutropenia (29.2%/14.3%/33.3%), decreased appetite (45.8%/71.4%/26.7%), thrombocytopenia (66.7%/28.6%/23.3%) and weight loss (16.7%,/42.9%/6.7%). CONCLUSION Selinexor monotherapy demonstrated encouraging intratumoral penetration and efficacy, with durable disease control in rGBM. Monotherapy dose at 80 mg QW is recommended for further development in rGBM. A phase 1/2 study of combination therapy for newly diagnosed or rGBM has been initiated (NCT04421378).

scholarly journals POS0698 BIIB059 DEMONSTRATED A CONSISTENT THERAPEUTIC EFFECT ON SRI-4 RESPONSE ACROSS SUBGROUPS OF PARTICIPANTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN THE LILAC PHASE 2 STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 597-598
Author(s):  
R. Van Vollenhoven ◽  
R. Furie ◽  
K. Kalunian ◽  
S. Navarra ◽  
J. Romero-Diaz ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Response Rate ◽  
Small Sample ◽  
Statistical Testing ◽  
Type I ◽  
Phase 2 ◽  
Systemic Lupus ◽  
Research Support ◽  
Chemokine Production

Background:Type I interferons and other inflammatory mediators derived from plasmacytoid dendritic cells (pDCs) are implicated in systemic lupus erythematous (SLE) pathology. BIIB059 is a humanized monoclonal antibody that targets blood dendritic cell antigen 2 (BDCA2), a pDC-specific receptor. The binding of BIIB059 to BDCA2 leads to rapid internalization of BDCA2 from the surface of pDCs and subsequent inhibition of interferon, cytokine, and chemokine production. In Part A of the 2-part, phase 2 LILAC study (NCT02847598), BIIB059 significantly reduced SLE activity, as evidenced by reduced total active joint count (primary endpoint) and higher SLE Responder Index (SRI-4)1 response (a secondary endpoint) versus placebo.2Objectives:To evaluate SRI-4 response for BIIB059 versus placebo at Week 24 in SLE participant subgroups.Methods:Enrollment in LILAC Part A was open to adults fulfilling ≥ 4 of 11 revised 1997 ACR criteria for classification of SLE, with ≥ 4 tender and ≥ 4 swollen joints, active skin disease, and positive lupus antibodies. Participants were randomized to receive either BIIB059 450 mg or placebo subcutaneously every 4 weeks for 20 weeks (with an additional dose at Week 2). SRI-4 response at Week 24 was analyzed in subgroups, though analyses were limited by small sample sizes and were not powered for statistical testing.Results:In LILAC Part A, 64 and 56 participants were dosed with BIIB059 450 mg and placebo, respectively. At week 24, SRI-4 response rate was observed in favor of BIIB059 regardless of the baseline disease activity, such as SLEDAI-2K <10 versus ≥10, presence of BILAG-2004 grade A or B arthritis, oral corticosteroid usage, positivity for anti-ds DNA autoantibody and/or complement status, with point estimates for least-squares mean differences as well as corresponding 95% CIs consistently favoring BIIB059 (Figure 1). The incidence of adverse events in the overall study population was similar between the placebo and BIIB059 groups.2Conclusion:BIIB059 treatment was associated with greater SRI-4 response rate, consistent among different subgroups of baseline disease activity as measured by SLEDAI-2K and BILAG-2004, glucocorticoid dosage, and serology. These findings provide additional evidence of the potential benefit of BIIB059 for the treatment of patients with active SLE.References:[1]Furie RA, et al. Arthritis Rheum. 2009;61(9):1143-1151. 2. Furie RA, et al. Arthritis Rheumatol. 2020;72(suppl 10). Abstract 0935.Acknowledgements:This study was sponsored by Biogen (Cambridge, MA, USA). Writing and editorial support was provided by Excel Scientific Solutions (Fairfield, CT, USA); funding was provided by Biogen.Disclosure of Interests:Ronald van Vollenhoven Consultant of: AbbVie, AstraZeneca, Biotest, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, UCB, Grant/research support from: AbbVie, Arthrogen, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, UCB, Richard Furie Consultant of: Biogen, Grant/research support from: Biogen, Kenneth Kalunian Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, Equillium, Genentech, Gilead, ILTOO, Janssen, Nektar, Roche, Viela, Grant/research support from: Lupus Research Alliance, Pfizer, Sanford Consortium, Sandra Navarra Speakers bureau: Astellas, Johnson & Johnson, Novartis, Pfizer, Consultant of: Biogen, Grant/research support from: Biogen, Juanita Romero-Diaz Consultant of: Biogen, Boehringer Ingelheim, Victoria Werth Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Gilead, GlaxoSmithKline, Janssen, Kyowa Kirin, Resolve, Viela, Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, XIAOBI HUANG Shareholder of: Biogen, Employee of: Biogen, HUA CARROLL Shareholder of: Biogen, Employee of: Biogen, Cristina Musselli Shareholder of: Biogen, Employee of: Biogen, Catherine Barbey Shareholder of: Biogen, Employee of: Biogen, NATHALIE FRANCHIMONT Shareholder of: Biogen, OMass Therapeutics, Employee of: Biogen

A multicenter, randomized phase 1b/2 study of gemcitabine and cisplatin with or without CPI-613 as first-line therapy for patients with advanced unresectable biliary tract cancer (BilT-04).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4158-TPS4158
Author(s):  
Vaibhav Sahai ◽  
Amy E. Chang ◽  
Oxana V. Crysler ◽  
David Bing Zhen ◽  
Muhammad Shaalan Beg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Biliary Tract ◽  
Alternative Hypothesis ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase 2 ◽  
First Line ◽  
Eligibility Criteria ◽  
Phase 1B ◽  
Gemcitabine And Cisplatin

TPS4158 Background: Patients (pts) with advanced biliary tract cancers (BTC) have poor prognosis despite systemic chemotherapy. Gemcitabine and cisplatin is a standard first-line systemic therapy with an overall response rate (ORR) of 26% and a median overall survival of 11.7 months. This investigator-initiated, multi-institutional phase 1b/2 trial is designed to investigate the role of gemcitabine, cisplatin and CPI-613 in pts with advanced BTC. CPI-613 is a stable intermediate of a lipoate analog that inhibits pyruvate dehydrogenase and a-ketoglutarate dehydrogenase enzymes of the tricarboxylic (TCA) cycle preferentially within the mitochondria of cancer cells. Methods: Key eligibility criteria include histologically confirmed, metastatic or unresectable BTC (intra- or extra-hepatic and gallbladder) without prior systemic treatment, measurable disease per RECIST v1.1, and ECOG PS 0-1. Primary objective of the phase 1b portion (n = 20 pts; TiTE-CRM methodology) is to determine the recommended phase 2 dose of the combination, and for the phase 2 portion, ORR (n = 48-58 pts; 2:1 randomization). Assuming a null hypothesis ORR of 25% and an alternative hypothesis of 43%, this ongoing trial has at least 80% power with a one-sided alpha of 0.05 to identify treatment efficacy of the study arm. Secondary objectives include evaluation of progression-free survival, overall survival, and safety in this patient population. Exploratory objectives include identification of molecular markers of response and resistance in tumor samples and serially collected blood (pre-, on-, and post-therapy), including whole exome/transcriptomic analysis, and immunohistochemical staining (PDK, PDH, KGDH, SOD2 and CD79a). Gemcitabine 1000 mg/m2, cisplatin 25 mg/m2 with or without CPI-613 (dose levels: 500 mg/m2, 1000 mg/m2, 1500 mg/m2, and 2000 mg/m2) will be given IV on days 1 and 8 every 21 days. In the absence of disease progression, pts may continue therapy for up to 2 years. Total accrual goal is 68-78 evaluable pts. To date, 5 of planned 20 pts enrolled on the phase 1b portion are without dose limiting toxicity. Clinical trial information: NCT04203160.

scholarly journals Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial

2020 ◽  
Vol 8 (1) ◽  
pp. e000798
Author(s):  
Lu Xie ◽  
Jie Xu ◽  
Xin Sun ◽  
Wei Guo ◽  
Jin Gu ◽  
...  
Keyword(s):  
Pulmonary Metastases ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Open Label Phase ◽  
High Grade Osteosarcoma

BackgroundResults of our previous study showed high objective response but short-term activity of apatinib in advanced osteosarcoma. We aimed to investigate the activity of apatinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy.MethodsThis open-label, phase 2 trial was conducted at Peking University People’s Hospital. We enrolled patients with advanced osteosarcoma progressed after chemotherapy. Patients received 500 mg apatinib orally once daily plus 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) and clinical benefit rate at 6 months, which were based on RECIST V.1.1.Results43 patients were enrolled between January 25 and September 4, 2018. With median follow-up time of 48.3 (Q1, Q3, 30.6, 66.6) weeks, 13 (30.23%, 95% CI 17.2%, 40.1%) of 43 patients were progression free at 6 months and the 6-month PFS rate was 50.9% (95% CI 34.6%, 65.0%). Until final follow-up, the objective response rate was 20.9% (9/43) and two patients with durable disease control were observed. Patients with programmed cell death 1 ligand-1 (PD-L1) tumor proportion score ≥5% and pulmonary metastases tended to have a longer PFS in comparison to the others (p=0.004 and 0.017, respectively). Toxic effects led to dose reductions, or interruptions, or both in 24 (55.8%) of 43 patients and permanent discontinuation in 4 (9.3%) patients. There were no treatment-related deaths.ConclusionsAlthough the combination of apatinib and camrelizumab seemed to prolong PFS in comparison to single agent apatinib in treating advanced osteosarcoma, it did not reach the prespecified target of 6-month PFS of 60% or greater. Overexpression of PD-L1 and the presence of pulmonary metastases only were associated with longer PFS.Trial registration numberNCT03359018.

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