Phase II trial of gemcitabine (G) with pazopanib (P) or gemcitabine with docetaxel (T) in advanced soft tissue sarcoma (STS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11008-11008
Author(s):  
Neeta Somaiah ◽  
Brian Andrew Van Tine ◽  
Elizabeth Goodwin Hill ◽  
Mohammed M. Milhem ◽  
Scott Schuetze ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Comparable Efficacy ◽  
Rank Test ◽  
Open Label ◽  
Exact Test ◽  
Phase 2 Trial ◽  
Grade 3 ◽  
To Receive ◽  
Clinical Trial Information ◽  
Alternative Regimen

11008 Background: P is a multi-tyrosine kinase inhibitor with efficacy in many sarcoma subtypes. We designed a trial to assess the benefit of adding P to G as an alternative regimen to the commonly used combination of G+T in pts with STS (NCT01593748). Methods: We performed an open-label, randomized phase 2 trial enrolling pts with advanced non-adipocytic STS who had received prior anthracycline based therapy. Pts were assigned (1:1 stratified randomization based on leiomyosarcoma and prior pelvic radiation) to receive G 1000 mg/m2 on days 1 and 8 with P 800 mg daily or G 900 mg/m2 on days 1 and 8 and T 100 mg/m2 on day 8, repeated q 3 wks. The primary objectives were estimating median PFS and rate of grade ≥3 adverse events (AEs). Secondary objectives included estimating the hazard ratio (HR) and response rates. Cross-over was allowed for RECIST progression. Sample size of 90 was derived based on the precision of 95% confidence intervals (CI) for reporting toxicity and PFS in each arm. Results: A total of 90 pts enrolled; 45 on each arm. Pt characteristics and results are detailed in Table. Median PFS was 4.1 months for each arm (p= 0.3, based on stratified log-rank test). The clinical benefit rate (PR+SD) was 29% for each arm (p>0.99, based on Fisher’s exact test). The rate of related grade ≥3 AEs were 20.6% with G+T and 19.9% with G+P. Related grade ≥3 AEs (%) occurring in ≥10% of pts (G+T; G+P): anemia (36, 20), fatigue (29; 13), low platelets (56; 51), low neutrophils (20; 49), AST increase (2; 13) and hypertension (2; 20). Conclusions: This study demonstrates comparable efficacy between G+P and G+T, suggesting that G+P can be considered for second-line therapy in advanced non-adipocytic STS. Pt Characteristics and Results. Clinical trial information: NCT01593748. [Table: see text]

Expanded analyses of napoli-1: Phase 3 study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 234-234 ◽  
Author(s):  
Li-Tzong Chen ◽  
Daniel D. Von Hoff ◽  
Chung-Pin Li ◽  
Andrea Wang-Gillam ◽  
Gyorgy Bodoky ◽  
...  
Keyword(s):  
Sensitivity Analyses ◽  
Open Label ◽  
Phase 3 ◽  
Open Label Study ◽  
Prior Therapy ◽  
Previously Treated ◽  
Grade 3 ◽  
Intent To Treat ◽  
To Receive ◽  
Clinical Trial Information

234 Background: MM-398 is a nanoliposomal encapsulation of irinotecan. OS in the ITT population was significantly longer with MM-398+5FU/LV over 5FU/LV alone, and the most frequent grade 3+ AEs included neutropenia, fatigue, and GI effects (diarrhea and vomiting). Expanded, pre-specified analyses of the Phase 3 study are presented. Methods: Patients (n=417) with mPAC previously treated with gemcitabine-based therapy, were randomized 1:1:1 in an open-label study to receive: (A) MM-398 (120 mg/m2 IV over 90 min) q3w; (B) 5FU (2,000 mg/m2 over 24 h) plus racemic leucovorin (LV) (200 mg/m2 over 30 min) x 4w followed by 2w rest; or (C) combination of MM-398 (80 mg/m2 IV over 90 min) prior to 5FU (2,400 mg/m2 over 46 h) and racemic LV (400 mg/m2 over 30 min) q2w. The primary endpoint was OS. The Intent To Treat (ITT) population included all randomized patients; the Per Protocol (PP) population included patients who received at least 80% of the target dose in the first 6 weeks and did not violate any inclusion/exclusion criteria. Results: Analysis of the PP populations confirmed the favorable OS, which was also reflected by the PFS, ORR and CA19-9 levels, of the combination MM-398+5FU/LV arm over the control 5FU/LV arm. The MM-398 monotherapy arm did not show a statistically significant improvement in OS compared with the control arm. Analysis of subgroups, based on pretreatment characteristics including stage at diagnosis, time since initial histological diagnosis, prior lines of therapy, time since last prior therapy, and CA19-9 levels, consistently favored OS for the MM-398+5FU/LV arm over the 5FU/LV arm. Conclusions: Expanded analysis of the PP population and sensitivity analyses support the favorability of MM-398+5FU/LV over 5FU/LV, with a manageable safety profile. Clinical trial information: NCT01494506. [Table: see text]

Camrelizumab plus apatinib in patients with advanced cervical cancer: A multicenter, open-label, single-arm, phase II trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6021-6021
Author(s):  
Chunyan Lan ◽  
Xin Huang ◽  
Jing-Xian Shen ◽  
Yin Wang ◽  
Ying Xiong ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Objective Response ◽  
Previous Treatment ◽  
Rank Test ◽  
Advanced Cervical Cancer ◽  
Open Label ◽  
Ecog Performance Status ◽  
Grade 3

6021 Background: Camrelizumab is a fully humanized, monoclonal antibody against PD-1. We aimed to assess the efficacy and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor targeting VEGFR2, in patients with advanced cervical cancer. Methods: In this open-label, single-arm, phase 2 study done at four centres in China, eligible patients were aged 18–70 years, had an ECOG performance status of 0 or 1, progressed after at least one line of systemic chemotherapy for metastatic, recurrent or persistent cervical cancer, and had measurable disease. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once daily. Treatment continued until disease progression, unacceptable toxicity, and withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by RECIST version 1.1. An optimal Simon two-stage design was employed to test the null hypothesis of a 17% ORR versus 35% alternative (1-sided alpha 0.10, 80% power), if > 3 responses out of the first 16 patients were observed, then the study would continue to enroll a total of 44 patients. Results: Between Jan 21st, 2019, and Aug 1st, 2019, 45 patients were enrolled and received study treatment (safety population). The median age was 51 (range, 33–67) years. Median previous treatment lines were 2 (range, 1–4). As of Jan 22, 2020, median follow-up was 9.2 months (range, 2.4–12.2). 25 (59.5%; 95%: CI 44.7–74.4) of 42 patients who had at least one post-baseline tumor assessment (efficacy evaluable population) achieved an objective response, including two (4.8%) complete response, and 23 (54.8%) partial response. Median duration of response was not reached. The disease control rate was 88.1% (37/42). Median progression-free survival (PFS) was 7.6 months (95% CI: 5.8–not reached). 31 (68.9%) patients had grade ≥ 3 treatment-related adverse events (TRAEs). Grade ≥ 3 TRAEs occurring in ≥ 5% of patients were hypertension (24.4%), anemia (20.0%), fatigue (15.6%), γ-glutamyltransferase increased (13.3%), neutropenia (6.7%), and thrombocytopenia (6.7%). In post-hoc analyses, objective response was noted in 20 (69%) of 29 patients with PD-L1-positive tumors, and in 5 (50.0%) of 10 patients with PD-L1-negative tumors (Chi-square test, P = 0.281). PFS was longer in patients with PD-L1-positive tumors than patients with PD-L1-negative tumors (median PFS: 9.6 versus 5.3 months; log-rank test, P = 0.017). Conclusions: Camrelizumab plus apatinib showed promising antitumor activity and tolerable toxicities in patients with advanced cervical cancer. Clinical trial information: NCT03816553.

ARMOR2: Galeterone in progressive CRPC patients who have failed oral therapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 71-71 ◽  
Author(s):  
Mary-Ellen Taplin ◽  
Robert B. Montgomery ◽  
Keyword(s):  
Study Drug ◽  
Oral Steroid ◽  
Open Label ◽  
Phase 2 Trial ◽  
Treatment Naïve ◽  
Psa Response ◽  
Steroid Analog ◽  
Grade 3 ◽  
Clinical Trial Information

71 Background: Galeterone is a first-in-class multitargeted oral steroid analog; it suppresses prostate cancer by a combination of AR modulation (antagonism and degradation) and CYP17 inhibition. Safety and proof of concept of galeterone in CRPC was assessed in ARMOR1. Galeterone was reformulated by spray dry dispersion technology (SDD) to optimize PK and remove food effect. ARMOR2 (NCT 01709734) is an open label, 2-part phase 2 trial that evaluates safety and efficacy of SDD galeterone in 4 populations of CRPC patients. These results report Part 1. Methods: Objectives of Part 1: confirm dose equivalence of SDD formulation with evaluation of PK, safety and PSA response. Metastatic (M1) and non-metastatic (M0) treatment naïve CRPC pts enrolled to groups of 1,700, 2,550 or 3,400 mg PO daily. An abiraterone refractory (Abi-R) group of 3 patients opened at 2,550mg. Results: 28 were enrolled in part 1. Safety: All groups were safe by IMC assessment. There were 4 grade 3 adverse events. 2 were unrelated to study drug. 2 had transient G3 ALT elevations (did not recur with rechallenge). There was no AME: supplemental steroids were not required. G4 angioedema occurred in a pt receiving lisinopril (known association with angioedema). Efficacy: PSA response was improved compared to ARMOR1 (AACR 2012. Taplin et al abstract: CT-07). At early follow up Abi-R pts showed improvements in PSA with 1 PSA30% response, 2 with stablized PSA (decline in PSA-V from +0.44 to -0.39 ng/day). Conclusions: Galeterone in SDD formulation is tolerated at doses up to 3,400mg daily. SDD galeterone provides improved PSA response and durability vs. prior formulation. There is evidence of activity in abiraterone refractory patients. Clinical trial information: 01709734. [Table: see text]

SOPHIA analysis by chemotherapy (Ctx) choice: A phase III (P3) study of margetuximab (M) + Ctx versus trastuzumab (T) + Ctx in patients (pts) with pretreated HER2+ metastatic (met) breast cancer (MBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1040-1040 ◽  
Author(s):  
Santiago Escrivá ◽  
Seock-Ah Im ◽  
Fatima Cardoso ◽  
Javier Cortes ◽  
Giuseppe Curigliano ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Phase Iii ◽  
Rank Test ◽  
Test Results ◽  
Open Label ◽  
Innate And Adaptive Immunity ◽  
Antiproliferative Effects ◽  
Primary Endpoints ◽  
Grade 3 ◽  
Clinical Trial Information

1040 Background: Despite advances, pretreated HER2+ MBC remains incurable with ongoing need for new therapies. Investigational M has similar HER2 binding and antiproliferative effects as T. Relative to T, M Fc engineering increases binding affinity for both variants of activating Fc receptor (FcR) CD16A and decreases affinity for inhibitory FcR CD32B, coordinately activating innate and adaptive immunity. In a Phase 3 (P3) trial, M prolonged PFS over T (Table). Second interim OS results from Sept 2019 also favor M (hazard ratio [HR], 0.89; 95% CI 0.69–1.13; nominal P=0.326). Methods: SOPHIA (NCT02492711), an open-label P3 trial, enrolled pts with HER2+ MBC after pertuzumab and 1–3 lines of prior treatment (Tx) for MBC. Randomization was 1:1 to M (15 mg/kg IV q3w + Ctx) or T (6 [8 for loading dose] mg/kg IV q3w + Ctx), stratified by met sites (≤2, >2), lines of Tx for met disease (≤2, >2), and Ctx choice, including capecitabine (Cap), eribulin (Eri), gemcitabine (Gem), or vinorelbine (Vin). Primary endpoints were central blinded PFS and OS, assessed sequentially using the stratified log-rank test. Results: Investigator chemotherapy choices and results by chemotherapy are shown in the table. Subjects receiving Eri and Gem had the lowest PFS hazards ratios (HRs), favoring M over T, although no statistical significance of individual chemotherapy subgroups was seen. There was variable toxicity among Ctx subgroups, and fewer subjects receiving Cap had Ctx related Grade 3 or higher (>=Gr 3) AEs. In this unblinded study, more subjects on M than T in all subgroups discontinued Ctx while continuing study antibody. Conclusions: In combination with chemotherapy in pretreated HER2+ MBC, M improved PFS over T. Safety was manageable in all Ctx subgroups. Differences among HRs for chemotherapy subgroups may be driven by selection bias and/or sensitivity differences. Clinical trial information: NCT02492711 . [Table: see text]

Preliminary safety analysis of phase II open-label NIVACOR trial (GOIRC-03-2018) in patients with advanced colorectal cancer RAS or BRAF mutated.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 37-37
Author(s):  
Angela Damato ◽  
Annalisa Berselli ◽  
Francesco Iachetta ◽  
Alessandra Romagnani ◽  
Mario Larocca ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Final Analysis ◽  
Safety Analysis ◽  
Open Label ◽  
Flat Dose ◽  
Grade 3 ◽  
To Receive ◽  
Dose Delay ◽  
Clinical Trial Information

37 Background: NIVACOR trial is an open-label, multicentric Italian phase II trial of FOLFOXIRI/bevacizumab in association with an anti-PD1 antibody, nivolumab, in patients (pts) with metastatic colorectal cancer (mCRC). We report preliminary safety analysis by an Independent Monitoring Committee. Methods: Pts with mCRC RAS or BRAF mutated, regardless microsatellite status and eligible to receive a first line treatment will be enrolled. FOLFOXIRI/bevacizumab (BEV) in association with nivolumab (NIV) was administered every 2 weeks for 8 cycles (induction) followed by BEV plus NIV every 2 weeks (maintenance) until PD or unacceptable toxicities. BEV was administered intravenously at dose of 5 mg/kg and NIV intravenously as a flat dose of 240 mg every 2 weeks. The primary endpoint was the ORR. The safety is assessed after the inclusion of the 10th patient, receiving ≥1 dose. Results: As of September 20, 2020, 25/70 pts are enrolled. The first 10 pts were evaluated for preliminary safety analysis. Median age was 58 years (32-66), 60% of pts were male, median cycles of treatment was 5.5 (1-9). 100% were KRAS G12D mut and BRAF wild type, respectively, and 2% MSI-H/dMMR. 7/10 pts experienced at least one AE related to FOLFOXIRI/BEV and 2/10 related to NIV. The most frequent grade 1-2 AEs related to FOLFOXIRI/BEV were nausea and vomiting 4(57%), fatigue 5(71%), and diarrhea 5(71%); 3(43%) pts had grade 3-4 neutropenia, and 1(14%) febrile neutropenia. Only 2 pts developed grade 1-2 AEs related to NIV represented by rash (50%) and salivary gland infection (50%); no grade 3-4 was reported. One of pts with dose delay because of serious AES (proteinuria) BEV related, and one patient discontinued due to serious AEs (ileo-urethral fistula) not related to NIV. Conclusions: Combination of FOLFOXIRI/BEV and NIV was generally well tolerated and showed an acceptable toxicity profile. The final analysis will be scheduled at the end of enrollment. Clinical trial information: NCT04072198.

Phase II study of pembrolizumab plus capecitabine and bevacizumab in microsatellite stable (MSS) metastatic colorectal cancer (mCRC): Interim analysis.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 77-77
Author(s):  
Andrea Grace Bocobo ◽  
Renee Wang ◽  
Spencer Behr ◽  
Julia C. Carnevale ◽  
Pelin Cinar ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Phase 2 ◽  
Open Label ◽  
Eligibility Criteria ◽  
Stage Design ◽  
Phase 2 Trial ◽  
Best Response ◽  
Grade 3 ◽  
Clinical Trial Information ◽  
Therapy Treatment

77 Background: MSS mCRC rarely responds to pembrolizumab monotherapy, but capecitabine and bevacizumab may induce immune-stimulatory effects. This study evaluates the safety, tolerability and preliminary efficacy of pembrolizumab in combination with capecitabine and bevacizumab in MSS mCRC. We present results at the planned interim analysis. Methods: Design:single-arm, open-label, single-site phase 2 trial with a safety lead-in to confirm the recommended phase 2 dose (RP2D) for capecitabine and expansion cohorts. Per the Simon’s 2-stage design, ≤1 response in 29 patients (pts) requires trial suspension. Key eligibility criteria: MSS mCRC with stable disease (SD) or progressive disease (PD) on prior fluoropyrimidine-based therapy. Treatment: RP2D PO capecitabine on days 1-14 plus 200 mg IV pembrolizumab and 7.5 mg/kg IV bevacizumab on day 1 in 21-day cycles. Pts are followed for toxicity and radiographic response. Results: From 04/2018-09/2020, 29 pts were enrolled, of whom 15 (52%) were female; 21 (72%) white; and median age was 55 years (range 36-77 years). Prior therapies: 2 (7%) pts had SD and 27 (93%) pts had PD on fluoropyrimidine-containing regimens; 24 (83%) pts had prior exposure to bevacizumab. The RP2D for capecitabine was 1000 mg/m2 PO BID, with no dose limiting toxicities observed. Complete toxicity data are available for 25 off-treatment pts. The most common related adverse events (AEs) were palmar-plantar erythrodysesthesia (PPE) (64%) and fatigue (68%). Grade ≥3 related AEs occurred in 9 (36%) pts, including immune-related AEs of Grade 3 dyspnea, hypophosphatemia, and pancreatitis in 1 pt each. Treatment related AEs leading to dose interruptions, reductions, or delays occurred in 15 (60%) pts, most commonly PPE in 13 (52%) pts. No pt had a related AE leading to treatment discontinuation or death. Disposition: of 29 pts enrolled, 24 were removed for PD and 1 was removed for an unrelated AE. Best response by RECIST 1.1 in 23 evaluable pts: partial response (PR) in 2 (9%); SD in 14 (61%); PD in 7 (30%). Median time on treatment was 6 months (range 2-26 months). Conclusions: Combination of pembrolizumab with capecitabine and bevacizumab was found to be tolerable with an expected toxicity profile in MSS mCRC pts. With 2 responses, the study met interim analysis criteria to continue accrual. Tissue and blood-based immune correlatives are planned. Clinical trial information: NCT03396926.

Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced non-clear cell renal cell carcinoma (nccRCC) (HCRN GU16-260-Cohort B).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4510-4510
Author(s):  
Michael B. Atkins ◽  
Opeyemi Jegede ◽  
Naomi B. Haas ◽  
David F. McDermott ◽  
Mehmet Asim Bilen ◽  
...  
Keyword(s):  
Clear Cell ◽  
Metastatic Lesion ◽  
Limited Information ◽  
Cell Renal Cell Carcinoma ◽  
Best Response ◽  
Treatment Naïve ◽  
Correlative Studies ◽  
Grade 3 ◽  
To Receive ◽  
Clinical Trial Information

4510 Background: The HCRN GU16-260 trial reported on the efficacy and toxicity of nivo monotherapy in treatment naïve clear cell RCC (Cohort A) and the efficacy of nivo/ipi salvage therapy in pts with tumors resistant to initial nivo monotherapy (Atkins JCO 2020.38.15_suppl.5006). Limited information is available on the effects of such an approach in pts with advanced nccRCC. Methods: Eligible pts with treatment-naïve nccRCC received nivo 240mg IV q2 wk x 6 doses followed by 360mg IV q3 wk x 4 doses followed by 480 mg q4 wk until progressive disease (PD), toxicity, or completion of 96 wks of treatment (Part A). Pts with PD prior to or stable disease (SD) at 48 wks (pSD) were potentially eligible to receive salvage nivo (3mg/kg) /ipi (1 mg/kg) q3 wk x 4 doses followed by q4 wk nivo maintenance for up to 48 wks (Part B). All pts were required to submit tissue from a metastatic lesion obtained within 12 months (mo) prior to study entry and prior to enrolling on Part B for correlative studies. Results: 35 pts with nccRCC were enrolled between 5/2017 and 12/2019 at 12 participating HCRN sites. Median age 63 (range 35-84 years); 89% male. IMDC favorable 8 (23%), intermediate 18 (51%) and poor risk 9 (26%). Of the 35 pts 19 (54%) had papillary, 6 (17%) chromophobe and 10 (29%) unclassified histology. RECIST defined ORR was 5 of 35 (14.3%) [CR 2 (5.7%), PR 3 (8.6%)], SD 16 (45.7%), PD 14 (40.0%). Immune-related ORR was 8 of 35 (22.9%). RECIST ORR by histology was: papillary - 1/19 (5%); chromophobe - 1/6 (17%); unclassified - 3/10 (30%). 9 pts (26%) had tumors with sarcomatoid features with 3 (33%) (2 unclassified, 1 papillary) responding. Median PFS was 4.0 (2.7, 4.3) mo. 21 pts remain alive. None of the responders have progressed or died. 28 pts (25 PD, 3 pSD) were potentially eligible for salvage nivo/ipi (Part B), but 12 did not enroll due to symptomatic PD (2), grade 3-4 toxicity on nivo (3), or other including no biopsy tissue (7). In the 16 Part B pts, best response to nivo/ipi was: PR (1, 6%) – (unclassified/non-sarcomatoid); SD (7, 44%); PD (8, 50%). Grade 3 Treatment-related adverse events (TrAEs) were seen in 7/35 (20%) on nivo. Grade 3-5 TrAEs were seen in 7/16 (44%) on nivo/ipi with 1 pt experiencing sudden death. Correlative studies including PD-L1 status, WES and RNAseq are pending. Conclusions: Nivo monotherapy has limited activity in treatment naïve nccRCC with most responses (4 of 5) seen in pts with sarcomatoid and/or unclassified tumors. Toxicity is consistent with prior nivo studies. Salvage treatment with nivo/ipi was provided in 16 of 28 (57%) pts with PD/pSD on nivo monotherapy, with 1 response observed. Clinical trial information: NCT03117309.

Combining radiation therapy with anti-PD-1 for patients with advanced hepatocellular carcinoma: An open-label, single-center, single-arm clinical study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16117-e16117
Author(s):  
Jian-Xu Li ◽  
Ting-Shi Su ◽  
Xiao-Feng Lin ◽  
Yi-Tian Chen ◽  
Shi-Xiong Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trial ◽  
Radiation Therapy ◽  
Clinical Study ◽  
Cancer Staging ◽  
Advanced Hepatocellular Carcinoma ◽  
Single Center ◽  
Open Label ◽  
Grade 3 ◽  
Clinical Trial Information

e16117 Combining radiation therapy with anti-PD-1 for patients with advanced hepatocellular carcinoma: an open-label, single-center, single-arm clinical study Jian-Xu Li, Ting-Shi Su, Xiao-Feng Lin, Yi-Tian Chen, Shi-Xiong Liang, Bang-De Xiang; Guangxi Medical University Cancer Hospital, Nanning, China Abstract Research Funding: Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China. Guangxi Medical and Health Appropriate Technology Development and Application Project (No. S2019039), Guangxi, China. Background: Based on the results of recent studies, the PD-1 monoclonal antibodies have been approved to treat the patients with advanced hepatocellular carcinoma (HCC) by the FDA. Radiation therapy (RT) can enhance responsiveness to PD-1 monoclonal antibody by potential mechanisms. A phase Ⅱa study was conducted to assess the safety and the efficacy of combining RT with anti-PD-1 for patients with advanced hepatocellular carcinoma. Methods: Patients with advanced HCC were eligible. Stereotactic body radiation therapy (SBRT) were adopted, and the dose of radiation were Dt-PGTV 30-50 Gy/10fractions. Camrelizumab (200mg) were given intravenously every 3 weeks since the first day of RT until disease progression, or intolerable toxicity. Adverse events (AEs) and objective response rate (ORR) were summarized to assess the safety and efficacy. Results: From April 2020 to November 2020, 17 patients were enrolled (median age 54, range 32-69). 15 (88%) patients were male. 14 (82%) had ECOG performance score of 0. All the patients had Child-Pugh score A. 16 patients staged as Barcelona Clinic Liver Cancer staging C or China Liver Cancer staging Ⅲ. Extrahepatic metastases were identified in 11 (65%) patients. 13 (77%) patients were Hepatitis B virus infected. 15 (88%) patients had previously 2 lines or more chemotherapy. 9 (53%) patients had Alpha-fetoprotein level≥400 ng/ml. The ORR was 47%. The best response assessed by RECIST 1.1 was partial response (8 patients). Four patients had grade 3 immune-related adverse events (irAEs), including increased aspartate aminotransferase and alanine transaminase (n =1)，decreased hemoglobin (n =1)，decreased platelet count (n =1)，decreased neutrophil count (n =1). All grade 3 irAEs were mitigated with proper treatment. None treatment-related deaths occurred. Conclusions: In this study, RT combined with anti-PD-1 had an acceptable safety profile and indicated an effective treatment option in patients with unresectable HCC. Clinical trial information: NCT04193696. Clinical trial information: NCT04193696.

scholarly journals A multicenter phase II study of Q3 week or weekly paclitaxel in combination with bevacizumab for the treatment of metastatic or unresectable angiosarcoma

Rare Tumors ◽  
2018 ◽  
Vol 10 ◽  
pp. 203636131877177 ◽  
Author(s):  
Nam Bui ◽  
Nikhil Kamat ◽  
Vinod Ravi ◽  
Sant Chawla ◽  
Marti Lohman ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Progression Free Survival ◽  
Weekly Paclitaxel ◽  
Comparable Efficacy ◽  
Progression Rate ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Multicenter Phase ◽  
Grade 3 ◽  
To Receive

Paclitaxel (P) and bevacizumab (B) are agents that provide clinical benefit in advanced angiosarcoma (AS). The objective of this study was to assess the efficacy and safety of P-B in two different scheduled regimens. Patients were to receive P 200mg/m2 IV with B 15mg/kg IV every 21 days (Regimen A) or P 90mg/m2 IV weekly D1, 8, 15 with B 15mg/kg IV D1 of a 28 day cycle (Regimen B) x6 cycles. Maintenance B followed at a dose of 15 mg/kg intravenously once every 21 days. The primary end point was 4 month non-progression rate (NPR). A total of 16 patients were enrolled. 4 month NPR was 62.5% with median overall survival 16 months and median progression free survival 5.06 months. 11 patients made it to cycle 3 and were evaluable for response with 1 CR (9%), 4 PR (36%), 2 SD (18%), and 6 PD (36%). There were ten grade 3 toxicities and four grade 4 toxicities. The breakdown between the two regimens revealed comparable efficacy and safety. Paclitaxel and Bevacizumab is an active regimen in angiosarcoma. Q3 week and weekly paclitaxel appear similar in efficacy and safety.

Rituximab Therapy after Response to R-CHOP Induction Therapy for Patients with Previously Untreated Indolent Non-Hodgkin’s Lymphoma (NHL): Clinical Outcomes and Pharmacokinetics (PK)

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1295-1295
Author(s):  
Louis Fehrenbacher ◽  
Jonathan A. Polikoff ◽  
Robert Hermann ◽  
Haresh Jhangiani ◽  
Jean Bjerke ◽  
...  
Keyword(s):  
Phase Iii ◽  
Open Label ◽  
Community Based ◽  
Serious Adverse Events ◽  
Residual Concentration ◽  
Ann Arbor ◽  
Grade 3 ◽  
To Receive ◽  
Ongoing Phase

Abstract The addition of rituximab (R) therapy significantly improves PFS in patients with relapsedl/refractory disease responding after CHOP as well as responders after R-CHOP induction (van Oers, 2005). The aim of this study was to assess, in patients with previously untreated indolent NHL, the safety, efficacy and PK of additional R therapy in responders to R-CHOP induction. Between 10/01 and 08/06, 102 patients aged 28–84 (mean 57 yr) yrs with Ann Arbor Stage III (28.4%) or IV (71.6%) indolent NHL were treated on this Phase II single-arm, open-label, multi-center, community-based trial. Baseline LDH and β2 microglobulin were above normal in 20.6% and 66.3% of patients, respectively. Treatment consisted of 6 cycles of R-CHOP (cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2, and doxorubicin 50 mg/m2 all IV on Day 1 of each 21-day cycle; prednisone 100 mg/d po Days 1–5; and R 375 mg/m2 IV 2–3 days prior to first dose of CHOP and thereafter on Day 1 of each cycle). Patients with ongoing response (CR/CRu or PR) received R 375 mg/m2 weekly x 4, repeated every 6 months x 2 yrs, for a total of up to 16 R doses, within 28 days after completion of R-CHOP. Median follow-up was 39 mos. ORR after R-CHOP was 86.3% (95% CI: 78.3, 92.1), with CR/CRu 48% (95% CI: 38.0, 58.2). As measured from initiation of R-CHOP, PFS at 2 and 3 yrs was 75.2% (95% CI: 64.0, 83.3) and 67.3% (95% CI: 54.6, 77.2), respectively. OS at 2 and 3 yrs was 92.9% (95% CI: 85.7, 96.6) and 89.4% (95% CI: 81.2, 94.2), respectively. Infusion-related toxicity with R given after R-CHOP was less frequent than seen with R-CHOP in this study. The overall incidence of serious adverse events during R therapy given after R-CHOP was 8.5%, including 3 NCI-CTC grade 3/4 events: viral encephalitis (n=1), patellar fracture (n=1) & development of colon cancer (n=1). Serum R concentrations were collected over serial timepoints from 12 patients. Both pre- and end of infusion serum R concentrations were similar across cycles 2–4 of R therapy given after R-CHOP. R concentration was higher just prior to infusion of the first R dose given after R-CHOP due to residual concentration from the R-CHOP treatment. Concentrations were very low (< 10 ug/mL) just prior to initiation of the subsequent R cycles. During R therapy given after R-CHOP, serum R concentrations were similar to those previously reported during R monotherapy treatment (Berinstein, 1998). In summary, this study demonstrated that R therapy given after R-CHOP to be generally well-tolerated, and associated with 75.2% PFS and 92.9% OS at 2 yrs, and 67.3% PFS and 89.4% OS at 3 yrs. Moreover, the current study demonstrates that PK data from R induction can be extrapolated to R given after R-CHOP. The benefit of adding additional R therapy to responders to R-chemotherapy will be addressed in the analysis of the ongoing Phase III PRIMA study, wherein patients with advanced follicular lymphoma who respond to R-chemotherapy induction are randomized to receive further R therapy vs. observation.

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