scholarly journals 955 CORE1: phase 2, single arm study of CG0070 combined with pembrolizumab in patients with non muscle invasive bladder cancer (NMIBC) unresponsive to bacillus calmette-guerin (BCG)

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A1005-A1005
Author(s):  
Roger Li ◽  
Gary Steinberg ◽  
Donald Lamm ◽  
Ed Uchio ◽  
Vignesh Packiam ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Intravesical Therapy ◽  
Survival Duration ◽  
Phase 2 ◽  
Free Survival ◽  
Gm Csf ◽  
Coxsackie Adenovirus Receptor ◽  
Phase 2 Study

BackgroundCG0070, an oncolytic vaccine available as an intravesical therapy, is a serotype 5 adenovirus engineered to express GM-CSF and replicate in tumor cells with mutated or deficient RB (which results in increased of the transcription factor E2F). The CG0070 mechanism of action includes direct cell lysis in conjunction with immunogenic cell death which is enhanced in the presence of GM-CSF. In an initial phase 1 study as well as a subsequent phase 2 study, an overall CR rate of ~62% and a CR at 12 months (m) of 29% have been observed in patients with high risk NMIBC previously treated with BCG. Intravenous Pembrolizumab was recently approved by the FDA for patients with BCG-unresponsive CIS (with or without papillary tumors) with an overall complete RR of 41% and a 12m CR rate of ~20%. This phase 2 study (NCT04387461) will assess the potential synergy of the two agents in the treatment of BCG-unresponsive NMIBC.Methods35 patients with BCG-unresponsive CIS with or without concurrent Ta or T1 disease will be treated with intravesical (IVE) CG0070 at a dose of 1x10e12 vp in combination with pembrolizumab at a dose of 400 mg IV q6 weeks. CG0070 will be administered weekly x 6 as induction followed by weekly x 3 maintenance instillations at 3, 6, 9, 12, and 18m. Patients with persistent CIS or HG Ta at 3 m may receive re-induction with weekly x 6 CG0070. Pembrolizumab will be administered up to 24m. Assessment of response will include q 3m cystoscopy with biopsy, urine cytology, CTU/MRU, and mandatory bladder mapping biopsies at 12m.ResultsThe primary endpoint is CR at 12 m. Secondary endpoints will include CR at any time, progression free survival, duration of response, cystectomy free survival and the safety of the combination. Correlate assessments will include changes in the TME, systemic immune induction, viral replication and transgene expression. Baseline expression of PD-L1, coxsackie adenovirus receptor, E2F transcription factor as well as anti-adenovirus antibody titer will be correlated with tumor response. At this time the first 5 patients demonstrates 100% 3 m CR. Treatment related AE have been limited to transient grade 1-2 urinary frequency (3 patients) and grade 1 bladder spasm, hematuria, painful urination, thyroiditis, and flu-like symptoms (one patient/each). No grade 3, 4, 5 AE or SAE were observed.ConclusionsThe study is currently enrolling. Preliminary safety and efficacy data on 8 patients will be available by November 2021Trial RegistrationNCT04387461Ethics ApprovalIRB: CG2003C

scholarly journals Phase 2 study using oral thalidomide-cyclophosphamide-prednisone for idiopathic multicentric Castleman disease

Blood ◽  
2019 ◽  
Vol 133 (16) ◽  
pp. 1720-1728 ◽  
Author(s):  
Lu Zhang ◽  
Ai-lin Zhao ◽  
Ming-hui Duan ◽  
Zhi-yuan Li ◽  
Xin-xin Cao ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Progression Free Survival ◽  
Castleman Disease ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Multicentric Castleman Disease ◽  
End Point ◽  
Phase 2 Study ◽  
Grade 3

Abstract Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder. The anti–interleukin 6 (IL-6) therapy siltuximab is not available everywhere, and is not effective for over one-half of patients. Alternative treatment approaches are urgently needed. In the first iMCD clinical trial directed against a target other than IL-6 signaling, we investigated a thalidomide-cyclophosphamide-prednisone (TCP) regimen in newly diagnosed iMCD patients. This single-center, single-arm, phase 2 study enrolled 25 newly diagnosed iMCD patients between June 2015 and June 2018. The TCP regimen (thalidomide 100 mg daily for 2 years; oral cyclophosphamide 300 mg/m2 weekly for 1 year; prednisone 1 mg/kg twice a week for 1 year) was administered for 2 years or until treatment failure. The primary end point was durable tumor and symptomatic response for at least 24 weeks. Twelve patients (48%) achieved the primary end point with no relapse, 3 patients (12%) demonstrated stable disease, and 10 patients (40%) were evaluated as treatment failure. Even when considering all patients, there were significant (P < .05) improvements in median symptom score, IL-6 level, hemoglobin, erythrocyte sedimentation rate, albumin, and immunoglobulin G. Among responders, the median levels of all evaluated parameters significantly improved, to the normal range, after treatment. The regimen was well tolerated. One patient died of pulmonary infection and 1 patient had a grade 3 adverse event (rash); 2 patients died following disease progression. Estimated 1-year progression-free survival and overall survival were 60% and 88%, respectively. The TCP regimen is an effective and safe treatment of newly diagnosed iMCD patients, particularly when siltuximab is unavailable. This trial was registered at www.clinicaltrials.gov as #NCT03043105.

TRIDENT-1: A global, multicenter, open-label Phase II study investigating the activity of repotrectinib in advanced solid tumors harboring ROS1 or NTRK1-3 rearrangements.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS9637-TPS9637
Author(s):  
Robert Charles Doebele ◽  
Jessica Jiyeong Lin ◽  
Misako Nagasaka ◽  
Viola Weijia Zhu ◽  
Nashat Y. Gabrail ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Solid Tumors ◽  
Phase 1 ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Advanced Solid Tumors ◽  
Phase 2 ◽  
Resistance Mutations ◽  
Open Label ◽  
Phase 2 Study

TPS9637 Background: Repotrectinib is a next-generation ROS1/TRK inhibitor with > 90-fold greater potency than crizotinib against ROS1 and > 100-fold greater potency than larotrectinib against TRK. Preclinical studies demonstrated inhibitory activity of repotrectinib against ROS1 resistance mutations, including the solvent-front mutation (SFM) G2032R. In the phase 1 portion of the study, repotrectinib was found to be well tolerated with encouraging antitumor activity including a 91% confirmed overall response (cORR) in TKI-naïve ROS1+ NSCLC pts. In ROS1+ NSCLC pts who received 1 prior chemo and 1 prior TKI, the cORR was 57% at the clinical dose of 160 mg QD or above. Intra-cranial (IC) activity was observed in ROS1+ NSCLC pts with measurable CNS disease (100% IC-ORR in TKI-naïve and 75% IC-ORR in patients with 1 prior TKI). Encouraging antitumor activity was observed in pts with NTRK+ solid tumors. Methods: A global phase 2 study was initiated and is actively enrolling. The primary endpoint for the Phase 2 study is cORR assessed by BICR (Blinded Independent Central Review) using RECIST v1.1, in each expansion cohort in pts with advanced solid tumors that harbor a ROS1 or NTRK1/2/3 gene fusion. Secondary endpoints include duration of response (DOR), progression-free survival (PFS), overall survival (OS), IC-ORR, IC-PFS, and quality of life assessments. All pts need to have RECIST 1.1 measurable disease confirmed by BICR and ECOG performance score ≤1. Repotrectinib is administered at 160 mg QD for 14 days and, if tolerated, the dose can be increased to 160 mg BID. Approximately 320 pts (≥12 years old) will be enrolled into 6 defined expansion cohorts, depending on the status of previous treatment with TKIs and cancer types (see table below). Clinical trial information: NCT03093116 . [Table: see text]

scholarly journals The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lars Ny ◽  
Henrik Jespersen ◽  
Joakim Karlsson ◽  
Samuel Alsén ◽  
Stefan Filges ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Median Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
Epigenetic Therapy ◽  
Phase 2 ◽  
Free Survival ◽  
Phase 2 Study ◽  
Phase 2 Clinical Trial ◽  
Registration Number

AbstractPreclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. We report the results of the PEMDAC phase 2 clinical trial (n = 29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic uveal melanoma (UM). The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Objective responses and/or prolonged survival were seen in patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM.Trial registration ClinicalTrials.gov registration number: NCT02697630 (registered 3 March 2016). EudraCT registration number: 2016–002114-50.

scholarly journals RTID-12. PHASE 2 TRIAL OF TUMOR TREATING FIELDS (TTFIELDS) PLUS RADIATION THERAPY (RT) PLUS TEMOZOLAMIDE (TMZ) COMPARED TO RT PLUS TEMOZOLOMIDE IN NEWLY DIAGNOSED GLIOBLASTOMA (ndGBM)

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii196-ii196
Author(s):  
Rachel Grossman ◽  
Dror Limon ◽  
Felix Bokstein ◽  
Carmit Ben Harosh ◽  
Deborah Blumenthal ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Skin Toxicity ◽  
Phase 2 ◽  
Free Survival ◽  
Tumor Treating Fields ◽  
Phase 2 Trial ◽  
Phase 2 Study ◽  
Newly Diagnosed Glioblastoma ◽  
Early Progressive Disease

Abstract OBJECTIVE In the EF-14 phase 3 trial, TTFields 9200 kHz) added to maintenance TMZ increased median OS to 20.9 months versus 16.0 months with maintenance TMZ (p< 0.001) in ndGBM. Preclinical investigations showed that TTFields/RT have a synergistic effect. A pilot study (N=10) in ndGBM demonstrated the feasibility and safety of TTFields combined with RT/TMZ (Grossman Front Onc 2020). The only TTFields-related adverse event was array-associated skin toxicity. Median PFS was 8.9 months. Based on these encouraging results, this prospective, randomized phase 2 study [NCT03869242] in 60 patients further investigates if the addition of TTFields TMZ/RT treatment in ndGBM patients improves treatment efficacy and delays disease progression. METHODS Following debulking surgery or biopsy, 60 patients (≥18 years) with histologically confirmed GBM, KPS≥70 and life expectancy >3 months will be randomized 1:1 to: i) RT with concomitant TMZ/TTFields (200 kHz) for 6 weeks followed by up to 6 months of maintenance TMZ combined with TTFields (experimental arm) up to 24 months; or ii) RT with concomitant TMZ alone followed by maintenance TMZ combined with TTFields (control arm). Patients with early progressive disease, significant comorbidities precluding maintenance RT or TMZ or with implanted electronic devices will be excluded. The primary endpoint is the rate of progression free survival at 12 months (PFS12). Treatment with TTF will be continued until second progression or 24 months (the earlier of the two). All patients will be followed for survival. All adverse events will graded per CTCAE V5.0. The sample size of 60 patients provides 80% power with two-sided alpha level of 0.05 to detect a PFS12 of 46.5% with RT/TMZ/TTFields compared to 29.4% with RT/TMZ followed, respectively, by maintenance TMZ/TTFields (calculated from the RT/TMZ followed by maintenance TMZ/TTFields arm of the EF-14 trial). Follow-up will continue for >12 months from recruitment of the last patient.

scholarly journals Bortezomib in combination with fludarabine and cyclophosphamide for patients with relapsed or refractory mantle-cell lymphoma: results of the LYM-4003 study

2019 ◽  
Author(s):  
Xiao-xiao Wang ◽  
Yan Gao ◽  
Jie Jin ◽  
Jun-ning Cao ◽  
Ji-feng Feng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Response Duration ◽  
Severe Toxicity ◽  
Phase 2 ◽  
Open Label ◽  
Median Response ◽  
Free Survival ◽  
Overall Response

Abstract Background The LYM-4003 study was initiated to identify the maximum tolerated dose (MTD) of cyclophosphamide when combined with bortezomib and fludarabine in a phase 1b trial, and to assess the efficacy and safety of this combination in a phase 2 trial in patients with relapsed or refractory MCL. Methods Patients with relapsed or refractory MCL who had received at least one previous lines of treatment were enrolled in this single-arm, open-label, phase 1/2 trial at six major cancer centers in China. In phase 1, to identify the MTD of cyclophosphamide, 3 patient cohorts received escalating doses (150, 200, and 250 mg/m2) of intravenous cyclophosphamide on days 1, 2 of each 28-day cycle. Patients also received bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11, fludarabine 25 mg/m2 on days 1, 2, 3 of each 28-day cycle. In phase 2 study, patients received bortezomib and fludarabine plus the MTD of cyclophosphamide. Treatment in both phases to maximum 6 cycles of chemotherapy, continued until disease progression, or severe toxicity. The primary endpoint was overall response. The secondary endpoint was survival. We used the Kaplan-Meier method to estimate response duration, progression-free survival, and overall survival. Analysis was by intention to treat population. Results 40 patients were enrolled between April 8, 2011 and October 10, 2015, 9 in phase 1 and 34 (including three patients who received the MTD of cyclophosphamide in phase 1) in phase 2. In phase 1, we identified the MTD as 250 mg/m2 cyclophosphamide. In phase 2, grade 3–4 hematological toxicities included thrombocytopenia, leucopenia, neutropenia, and lymphopenia. Among 32 patients in phase 2, 23 (72%) had an overall response: 10 (31%) had a complete response and 13 (41%) had a partial response. The median follow-up time was 31.6 months. The median response duration was 26.3 months. The median progression-free survival was 21 months (95% CI 7.3–34.7), and the median overall survival was 32.4 months (95% CI 17.8–47.0). Conclusions Bortezomib in combination with fludarabine and cyclophosphamide is highly effective and well tolerated for patients with relapsed or refractory MCL. Trial registration ClinicalTrials.gov NCT01322776 (Registered on March 25, 2011)

scholarly journals Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma

Blood ◽  
2012 ◽  
Vol 119 (19) ◽  
pp. 4375-4382 ◽  
Author(s):  
Shaji Kumar ◽  
Ian Flinn ◽  
Paul G. Richardson ◽  
Parameswaran Hari ◽  
Natalie Callander ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase 2 ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Highly Active ◽  
Phase 2 Study ◽  
Significant Efficacy ◽  
Good Partial Response

Abstract Combinations of bortezomib (V) and dexamethasone (D) with either lenalidomide (R) or cyclophosphamide (C) have shown significant efficacy. This randomized phase 2 trial evaluated VDC, VDR, and VDCR in previously untreated multiple myeloma (MM). Patients received V 1.3 mg/m2 (days 1, 4, 8, 11) and D 40 mg (days 1, 8, 15), with either C 500 mg/m2 (days 1, 8) and R 15 mg (days 1-14; VDCR), R 25 mg (days 1-14; VDR), C 500 mg/m2 (days 1, 8; VDC) or C 500 mg/m2 (days 1, 8, 15; VDC-mod) in 3-week cycles (maximum 8 cycles), followed by maintenance with V 1.3 mg/m2 (days 1, 8, 15, 22) for four 6-week cycles (all arms) ≥ very good partial response was seen in 58%, 51%, 41%, and 53% (complete response rate of 25%, 24%, 22%, and 47%) of patients (VDCR, VDR, VCD, and VCD-mod, respectively); the corresponding 1-year progression-free survival was 86%, 83%, 93%, and 100%, respectively. Common adverse events included hematologic toxicities, peripheral neuropathy, fatigue, and gastrointestinal disturbances. All regimens were highly active and well tolerated in previously untreated MM, and, based on this trial, VDR and VCD-mod are preferred for clinical practice and further comparative testing. No substantial advantage was noted with VDCR over the 3-drug combinations. This trial is registered at www.clinicaltrials.gov (NCT00507442).

scholarly journals Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia

Blood ◽  
2016 ◽  
Vol 127 (1) ◽  
pp. 79-86 ◽  
Author(s):  
John C. Byrd ◽  
Joseph M. Flynn ◽  
Thomas J. Kipps ◽  
Michael Boxer ◽  
Kathryn S. Kolibaba ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Safety Profile ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Meaningful Difference ◽  
Phase 2 ◽  
Free Survival ◽  
Phase 2 Study ◽  
Key Points ◽  
Randomized Phase 2

Key Points Obinutuzumab monotherapy demonstrates an increased ORR with 2000 mg over 1000 mg, but no difference in progression-free survival. No meaningful difference was observed in the overall safety profile across the 2 treatment arms.

A phase 2 study of s-1 plus leucovorin in patients with untreated advanced cholangiocarcinoma (CCA).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 467-467
Author(s):  
Suebpong Tanasanvimon ◽  
Teerapat Ungtrakul ◽  
Nattaya Poovorawan ◽  
Napa Parinyanitikul ◽  
Chanida Vinayanuwattikun ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Primary Endpoints ◽  
Phase 2 Study ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Grade 3

467 Background: Patients with CCA usually present with advanced disease leading to the grave prognosis. Currently, cisplatin and gemcitabine is the standard treatment in advanced CCA. However, the CCA treatment outcomes are still poor and the options of treatment are quite limited. This study aimed to explore the efficacy and safety of S-1 plus leucovorin in patients with untreated advanced CCA. Methods: This single-arm two-center phase 2 study evaluated the efficacy and safety of S-1 40, 50 and 60 mg according to body surface area and leucovorin 15 mg , both given orally twice daily for one week, repeated every two weeks. Treatment was continued until complete 12 cycles, disease progression or unacceptable toxicity. The primary endpoints were overall response rate (ORR) and disease control rate (DCR) per RECIST version 1.1. The secondary endpoints were progression free survival (PFS), overall survival (OS) and toxicity. Results: Of total 32 patients and a median follow up time of 9.5 months, the ORR was 25% (95%CI 9.1-40.9) and the DCR was 62.5% (95% CI 44.8-80.2). In 25 response evaluable patients, the ORR was 32% (95% CI 12.4-51.7). The PFS was 8.0 (95%CI 5.59-10.4) months. The OS was 11.0 (95%CI 9.47-12.53). The most common grade 3 or 4 toxicities were anemia, mucositis and diarrhea. There was one patient discontinuing treatment due to treatment related toxicity. Conclusions: S-1 plus leucovorin was active and tolerable in patients with advanced CCA. Clinical trial information: TCTR20160313001.

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