Halo 110-101: Early safety results of pegvorhyaluronidase alfa (PEGPH20; PVHA) + cisplatin (C) + gemcitabine (G) ± atezolizumab (ATZ) in patients (pts) with locally advanced or metastatic cholangiocarcinoma (CCA) and gallbladder cancer (GBC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 408-408
Author(s):  
Do-Youn Oh ◽  
Mann Muhsin ◽  
Andrea J. Bullock ◽  
Ghassan K. Abou-Alfa ◽  
Rachna T. Shroff ◽  
...  
Keyword(s):  
Immune Cell ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Phase Clinical Trial ◽  
The Mean ◽  
The Individual ◽  
Dose Limiting Toxicity ◽  
Clinical Trial Information

408 Background: Standard of care for CCA/GBC is C-G therapy. MAbs (ATZ, pembrolizumab) targeting PD-L1 show promise in treating CCA/GBC. Hyaluronan (HA), which may impede drug and immune cell access, is high (67%) in CCA/GBC tumors. PEGPH20 enzymatically degrades HA. HALO 110-101 (NCT03267940) evaluates safety and activity of PEG-C-G-ATZ or PEG-C-G versus C-G in CCA/GBC pts. Methods: This study comprises two parts. In Run-In (RI) six pts were enrolled in PEG-C-G arm, then six pts in PEG-C-G-ATZ arm. Eight additional pts may be enrolled for tolerability. In Expansion (EX), up to 50 pts will be enrolled for efficacy. Treatment (Tx) cycle is 21 days (d). PEGPH20 dose is 3 μg/kg on d1, eight and 15 and ATZ dose is 1200 mg (one–three hours after PEGPH20) on d1 (PEG-C-G-ATZ only). C-G is dosed at 25 mg/m2 C and 1000 mg/m2 G on d2 and nine. In C-G arm (EX only), C-G is dosed on d1 and 8. Primary endpoints are ORR (RECIST v1.1), AEs (NCI CTCAE v4.03), laboratory/safety (RI only); secondary endpoints are PK; DOR, DCR, PFS; OS, OS by PD-L1 expression; ORR and DOR (imRECIST). Results: Eighteen pts have been enrolled (nine in each arm). The mean (SD) age is 57 (12.2) yrs in PEG-C-G and 69 (8.8) yrs in PEG-C-G-ATZ. 56% were men. All pts experienced ≥ 1 AE. The most common AEs are nausea, fatigue (50% each); decreased appetite (44%); anemia, constipation (39% each); thrombocytopenia, oedema peripheral, AST increased, myalgia (33% each). To date, there has been one dose-limiting toxicity (febrile neutropenia) in the PEG-C-G arm. There have been no deaths due to AEs. Conclusions: The overall safety profile of PEGPH20 + C + G ± ATZ is acceptable and consistent with safety observed for the individual components. There were no DLTs resulting in a dose reduction of PEGPH20, which is being dosed at 3 μg/kg in the EX phase. Clinical trial information: NCT03267940. [Table: see text]

HALO 110-101: A phase Ib, randomized, open-label study of PEGPH20 (pegvorhyaluronidase alfa) in combination with cisplatin (CIS) + gemcitabine (GEM) (PEGCISGEM) or atezolizumab and CIS + GEM (PEGCISGEMATEZO) in hyaluronan-high subjects with locally advanced or metastatic cholangiocarcinoma and gallbladder cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS543-TPS543 ◽  
Author(s):  
Mitesh J. Borad ◽  
Rachna T. Shroff ◽  
Ghassan K. Abou-Alfa ◽  
J. Randolph Hecht ◽  
Andrea J. Bullock ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
Immune Cell ◽  
Locally Advanced ◽  
Safety Data ◽  
Data Monitoring Committee ◽  
Open Label ◽  
Dosing Schedule ◽  
Primary Endpoints ◽  
Safety Parameters ◽  
Secondary Endpoints

TPS543 Background: Cholangiocarcinoma (CCA) is treated with CIS and GEM (CISGEM), but prognosis is poor. Hyaluronan (HA) accumulation in solid tumors may impede drug and immune cell access. PEGPH20 targets tumors that accumulate HA (HA-high). This study (NCT03267940) plans to enroll 70 subjects to evaluate the safety and activity of PEGPH20 + programmed cell death-ligand 1 (PD-L1) agent atezolizumab, (PEGCISGEMATEZO), & PEGPH20 + CISGEM (PEGCISGEM) in HA-high subjects with CCA and gallbladder cancer. Study will comprise initial run-in and expansion portions. Primary endpoints include incidence of AEs and other laboratory/safety parameters and ORR (RECIST v1.1). Secondary endpoints include PK parameters; DOR, DCR, PFS, and ORR (RECIST v1.1 and immune-modified RECIST); and OS and OS by PD-L1 expression. Methods: ~6 HA-high subjects will be enrolled in PEGCISGEM arm run-in portion and undergo at ≥1 cycle; subsequently, 6 HA-high subjects will enter the PEGCISGEMATEZO arm. Treatment period will be 21-day cycles. In the expansion portion, ~50 HA-high subjects will be enrolled and randomized in a 2:2:1 ratio into PEGCISGEMATEZO, PEGCISGEM, and CISGEM arms. PEGPH20 is planned to be administered at 3.0 μg/kg on Days 1, 8 and 15 of all cycles in both portions. ATEZO will be administered at 1200 mg 1–3 hours after PEGPH20 on Day 1 of each 21-day cycle in the PEGCISGEMATEZO arm in both portions. In the PEGCISGEM & PEGCISGEMATEZO arms, dosing schedule for CISGEM is the same during both portions, with administration of 25 mg/m2 CIS and 1000 mg/m2 GEM on Days 2 and 9 of each cycle. In CISGEM control arm (expansion only), dosing schedule will be on Days 1 and 8 of each cycle. Treatment will continue until death, withdrawal of consent, disease progression, or unacceptable toxicity. Tumor response will be evaluated using RECIST v1.1. AEs will be graded per NCI CTCAE v4.03. Tumor samples will be tested retrospectively for PD-L1 expression. Safety data will be periodically monitored by an independent data monitoring committee. Clinical trial information: NCT03267940.

Efficacy of entrectinib in patients (pts) with solid tumors and central nervous system (CNS) metastases: Integrated analysis from three clinical trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3017-3017 ◽  
Author(s):  
Salvatore Siena ◽  
Robert Charles Doebele ◽  
Alice Tsang Shaw ◽  
Christos Stelios Karapetis ◽  
Daniel Shao-Weng Tan ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Phase 1 ◽  
Locally Advanced ◽  
Integrated Analysis ◽  
Data Sets ◽  
Cns Metastases ◽  
Prior Therapy ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Clinical Trial Information

3017 Background: Entrectinib potently inhibits kinases encoded by the NTRK and ROS1 genes. It achieves therapeutic levels in the CNS with antitumor activity in intracranial tumor models. We report integrated data (31 May 2018 cut-off) from 3 Phase 1/2 entrectinib trials (ALKA-372-001, EudraCT 2012-000148-88; STARTRK-1, NCT02097810; STARTRK-2, NCT02568267) for a large cohort of adults with ROS1 fusion-positive NSCLC ( ROS1+) or NTRK fusion-positive solid tumors ( NTRK+), with/without baseline CNS metastases. Methods: Pts had locally advanced/metastatic NTRK+ or ROS1+ tumors by nucleic acid-based confirmation. Baseline CNS metastases were identified by CT/MRI. Tumor assessments were at wk 4, then every 8 wk by blinded independent central review (RECIST v1.1). Primary endpoints: ORR, DOR. Secondary endpoints: CBR, PFS, OS, intracranial efficacy and safety. Results: Most pts had ≥1 prior therapy; 33% had baseline CNS metastases. Outcomes for the ROS1+ NSCLC (n = 53) and NTRK+ solid tumors (n = 54; 24% sarcoma, 18% NSCLC) efficacy evaluable data sets are shown (table). Entrectinib was tolerable with a manageable safety profile; most treatment-related AEs were grade 1–2. Conclusions: Entrectinib induced clinically meaningful durable responses in pts with ROS1+ NSCLC or NTRK+ solid tumors with or without CNS disease. Clinical trial information: NCT02097810; NCT02568267. [Table: see text]

IMvigor 210, a phase II trial of atezolizumab (MPDL3280A) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 355-355 ◽  
Author(s):  
Jean H. Hoffman-Censits ◽  
Petros Grivas ◽  
Michiel Simon Van Der Heijden ◽  
Robert Dreicer ◽  
Yohann Loriot ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Antitumor Immunity ◽  
Immune Cell ◽  
Locally Advanced ◽  
Primary Endpoints ◽  
Immune Mediated ◽  
Platinum Based Chemotherapy ◽  
Metastatic Urothelial Carcinoma ◽  
Clinical Trial Information

355 Background: The ORR and survival of mUC patients (pts) who progress after platinum-based chemotherapy (pctx) are poor. Atezolizumab (atezo) reinvigorates antitumor immunity by targeting PD-L1 and has shown promising Ph 1 activity in mUC. Methods: IMvigor 210 cohort 2 (NCT02108652) enrolled 316 mUC pts who progressed during or following pctx. Pts received atezo at 1200 mg IV q3w until loss of clinical benefit. The SP142 IHC assay centrally assessed PD-L1 expression. Pts/investigators were blinded to PD-L1 status. Co-primary endpoints were confirmed ORR by RECIST v1.1 per central review (IRF) and modified (m) RECIST per investigator, which were met if null hypothesis (ORR = 10%) was rejected (α = 5%). ORR endpoints were stratified by PD-L1 tumor-infiltrating immune cell (IC) status: IC2/3, IC1/2/3, all comers. Results: Efficacy/safety-evaluable pts (N = 311) had a median age of 66 y, CrCl < 60 mL/min (35%) and ≥ 2 prior regimens for mUC (40%). Many had poor prognostic factors (Table). At 5/5/15 data cutoff (follow up ≥ 24 w), 43/47 responding pts had ongoing responses. Both IRF (Table) and mRECIST ORR correlated with IC status. Durable responses were seen including poor prognostic subgroups (Table). mDOR was not reached in any PD-L1 or prognostic subgroup. mPFS was 2.1 mo in all PD-L1 subgroups. Median treatment duration was 12 w (range 0-46). Treatment-related AEs (most commonly fatigue) occurred in 66% of pts (all Grade); 15% had G3-4 related AE and 4% had G3-4 immune-mediated AE. 27% of AEs led to dose interruption and 3% led to withdrawal. No renal toxicity was seen. Conclusions: IMvigor 210, the first Ph 2 study targeting PD-L1/PD-1 in mUC, demonstrated significantly improved ORR vs historic controls. Responses were durable and associated with higher PD-L1 IC expression; poor prognostic factors did not preclude response. Atezo was well tolerated, and a randomized Ph 3 study vs ctx is ongoing (IMvigor 211; NCT02302807). Clinical trial information: NCT02108652. [Table: see text]

Impact of a pre- and postoperative chemotherapy (Ctx) on overall survival (OS) and progression free survival (PFS) in locally advanced gastric cancer (LAGC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 156-156
Author(s):  
Ricarda Manth ◽  
H Schaefer ◽  
J Schroeder ◽  
G Spiessl ◽  
N Nuessler ◽  
...  
Keyword(s):  
Internal Control ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Initial Therapy ◽  
Tumor Board ◽  
Free Survival ◽  
Locally Advanced Gastric Cancer ◽  
Primary Surgery ◽  
Secondary Endpoints

156 Background: Perioperative Ctx has become standard of care for LAGC. Duration of pre- and post-op Ctx is a matter of debate. Our study evaluated effects of varying durations of pre- and post-op Ctx on PFS and OS. Secondary endpoints were toxicity, reasons for cessation of Ctx and response. We compared the outcome to a group of pts receiving no perioperative Ctx as an internal control. Methods: Pts with LAGC were included in a prospective cohort trial from a single institution from 2007 to 2015. Inclusion criteria were T1-T4, N0-3, M0, AEG (n=27) or gastric cancers (n=65). Initial therapy decisions were made by an interdisciplinary tumor board for all pts. Pts received DDP/5-FU (qw d28 mod FFCD-Protocol, Ychou et al. JCO 2011) for 2 mo, and a 3rd mo of pre-op Ctx in case of non-progression after 2 mo and proceeded to Ctx after surgery for a planned total of six mo of Ctx. Results: 92 pts (53 m; 39 f pts) with a median age of 69 ys (range 33-96) were included. A total of 74 pts were recommended periop Ctx and 18 primary surgery (S). A total of 67 (91%) of the periop Ctx received pre-op Ctx (NA) of which 47 (64%) received 3 mo of pre-op Ctx, 19 (26%) two mo, 1 pt (1%) one mo, and 7 pts refused preop Ctx (9%) of which only 3 proceeded to surgery. Only 53 pts (72 %) received post-op Ctx; 25 pts (34%) received three mo, 9 pts (12 %) two mo, and another 10 pts (14 %) one mo of postop Ctx. Nine pts (13%) in the NA group and 20 pts (39%) in the post-op Ctx group had to stop Ctx due to toxicity after 1 (n=11) and <2 (n=9) mo of Ctx. Only 23 pts (31%) received the planned pre- and postop Ctx of 6 mo in total. Up to 07/2016 a total of 36 deaths were observed (39%). 5 yr PFS was 49% in the group of periop Ctx vs 14% in the S group. PFS in pts receiving a total of < 4 mo of Ctx was 36% vs. 61% in pts receiving 6 mo of Ctx. 3 yr OS was 19% in the S group vs 48% in the Ctx group. The OS in pts receiving < 4 mo was 34% vs.43% in pts with 6 mo Ctx. A pCR after preop Ctx was observed in 2 pts, a PR in 47 pts, a SD in 12 pts, while a PD occurred in 3 pts only. Conclusions: Pre-op Ctx was considerably better tolerated than post-op Ctx and led to fewer Tx cessations. We found a better PFS for pts with >4 mo of periop Ctx, as well as OS was affected by a shorter duration of periop Ctx.

Combination checkpoint immunotherapy and cytotoxic chemotherapy: Pembrolizumab (Pembro) plus either docetaxel or gemcitabine in patients with advanced or metastatic urothelial cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 398-398 ◽  
Author(s):  
Primo Lara ◽  
Laurel Beckett ◽  
Yueju Li ◽  
Mamta Parikh ◽  
Daniel Robles ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Progression Free Survival ◽  
Organ Function ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Initial Cohort ◽  
Secondary Endpoints ◽  
Anti Tumor Activity ◽  
Dose Limiting Toxicity ◽  
Clinical Trial Information

398 Background: Metastatic urothelial cancer (mUC) is only modestly responsive to checkpoint inhibitor immunotherapy; e.g., the PDL1 inhibitor atezolizumab confers only a 16% tumor response rate (RR) in platinum-treated mUC. Chemotherapy is hypothesized to enhance tumoral neoantigen expression thus priming response to PD1-directed immunotherapy. Here we report results from the initial cohort of an investigator-initiated trial of Pembro plus either docetaxel or gemcitabine in platinum-treated mUC patients (pts). Methods: Primary endpoint was safety; secondary endpoints were overall RR and progression-free survival (PFS). Eligible pts had Zubrod PS 0-1, adequate end-organ function, and up to 2 prior lines of chemo (at least 1 platinum-based). Dose limiting toxicity (DLT) was any grade (Gr) 3+ non-heme toxicity, Gr3+ neutropenia w/ fever or infection, or Gr4 platelets (plts), or Gr3 plts with bleeding. In dose level (DL) 1, treatment consisted of Pembro 200 mg IV on D1 q3 weeks plus either docetaxel 75 mg/m2 on D1 (Arm 1) or gemcitabine 1000 mg/m2 on D1&D8 (Arm 2). Results: Overall 12 pts were enrolled in DL1, six in each arm. Median age was 69 years (range 45-84), 8 (67%) male, & 10 (83%) of white race. One pt in each arm had DLT: Gr3 hypophosphatemia in Arm 1, Gr3 diarrhea in Arm 2. Attributable Gr3+ toxicities were seen in 7 (54%). Most common Gr3+ AEs were anemia (5, 38%), fatigue (4, 31%), & neutropenia (4, 31%). There were no treatment related deaths; 3 died from tumor progression (PD). As of 10/2016, 4 pts remain on active therapy. In total 4 pts had confirmed response (1 CR, 3 PR), 2 had stable disease (SD), and 6 had PD for an overall RR of 33% and Disease Control Rate (DCR) of 50%. Arm 1 had an overall RR of 50% (1CR, 2PR, 1SD) and DCR of 67%. Arm 2 had an overall RR of 17% (1PR, 1SD) and DCR of 33%. Median PFS (overall, Arm 1 & 2) were 4.8, 5.7, and 3.7 months. Conclusions: Pembro 200 mg IV q3 weeks plus either full-dose docetaxel or gemcitabine is feasible in platinum-treated mUC pts. Encouraging anti-tumor activity for chemo-immunotherapy was seen in this ongoing study, particularly with Pembro+docetaxel. Further investigation of this approach is warranted. Clinical trial information: NCT02437370.

Transarterial infusion chemotherapy (TAI) combined with Sintilimab in locally advanced, potentially resectable hepatocellular carcinoma (HCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16593-e16593
Author(s):  
Li Xu ◽  
Yaojun Zhang ◽  
Xiaohui Wang ◽  
Mude Shi ◽  
Juncheng Wang ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Control Group ◽  
Resection Rate ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Infusion Chemotherapy ◽  
Conventional Tace ◽  
Secondary Endpoints ◽  
Transarterial Infusion ◽  
Clinical Trial Information

e16593 Background: Our previous studies showed that TAI with modified FOLFOX increased tumor response and resection rate compared with conventional TACE in advanced HCC. PD-1/PD-L1 inhibitors have been demonstrated promising value in HCC. This study aims to evaluate the efficacy and safety of FOLFOX-TAI combined with Sintilimab (a PD-1 inhibitor) in locally advanced, potentially resectable HCC. Methods: This prospective, nonrandomized controlled phase II study is recruiting 40 pts with locally advanced, potentially resectable HCC (localized to semi-liver with invasion to branch of the portal vein). Pts in the combined group receive repeated 3-week cycles of Sintilimab 200mg IV Day1 and TAI with FOLFOX Day2 (Oxaliplatin 130 mg/m2, Leucovorin 400 mg/m2, 5-FU 400 mg/m2 and 5-FU 2400 mg/m2, next 46 hours). Pts in the control group only received TAI. Tumor assessment with RECIST 1.1 was performed every 2 cycles. The pts gained visible tumor shrinkage and opportunity for resection received surgical hepatectomy. Pts with stable disease (SD) or unconfirmed progression disease (PD) will receive repeated cycles until confirmed PD or intolerable toxicity, with max cycles of 8 for TAI and 16 for Sintilimab. The primary endpoint is progression or postoperative relapse free survival (PFS). Secondary endpoints include ORR, DCR, resection rate, OS, and safety. Results: As of Jan 10, 2020, 33 eligible pts were enrolled. All treatment related AEs were grade 1 or 2, including transaminase and bilirubin increase, nausea, hypoalbuminemia, rash, leucopenia, thrombopenia, and weight loss. No irAE and treatment related SAE was observed. Conclusions: TAI combined with Sintilimab attributed to high surgical conversion rate and good safety profile for locally advanced, potentially resectable HCC. Clinical trial information: NCT03869034 .

scholarly journals Perioperative radiotherapy versus surgery alone for retroperitoneal sarcomas: a systematic review and meta-analysis

2020 ◽  
Vol 54 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Alexandros Diamantis ◽  
Ioannis Baloyiannis ◽  
Dimitrios E. Magouliotis ◽  
Maria Tolia ◽  
Dimitrios Symeonidis ◽  
...  
Keyword(s):  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Standard Of Care ◽  
Treatment Result ◽  
R0 Resection ◽  
Resection Rate ◽  
Free Survival ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Retroperitoneal Sarcomas

AbstractBackgroundThere is no clear evidence on whether radiotherapy (RT) improves treatment result in patients with retroperitoneal sarcomas (RPS).MethodsA systematic literature search was performed using PubMed, Scopus and CENTRAL databases. Data were retrieved from published comparatives studies in patients with RPS undergoing surgery alone or RT plus surgery. The primary endpoints were the 5-year OS and the median OS. The secondary endpoints were the recurrence-free survival (RFS) and the R0-resection rate. Continuous outcomes were calculated by means of weighted mean difference (WMD).ResultsTen out of 374 articles were analyzed. The median OS and the 5-year survival were significantly increased in patients treated with RT and surgery, compared to patients treated with surgery alone (p < 0.00001, p < 0.001). Median RFS was significantly increased in patients treated with either preoperative (p < 0.001) or postoperative (p = 0.001) RT compared to patients that underwent surgery alone. Finally, median R0-resection rate was similar between the two groups (p = 0.56).ConclusionRT along with radical surgery could be the standard of care in at least a subgroup of patients with RPS.

A randomized phase II study of individualized stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) with DEBDOX beads as a bridge to transplant in hepatocellular carcinoma (HCC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 223-223 ◽  
Author(s):  
Francis W. Nugent ◽  
Amir Qamar ◽  
Keith E. Stuart ◽  
Kari Galuski ◽  
Sebastian Flacke ◽  
...  
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
Locally Advanced ◽  
Bridge To Transplant ◽  
Class A ◽  
Randomized Phase Ii ◽  
Median Total Dose ◽  
Secondary Endpoints ◽  
Prescription Dose ◽  
Clinical Trial Information

223 Background: For HCC pts undergoing LT, local regional treatment as a "bridge" is standard to decrease tumor progression. The most common treatment is TACE, but the best bridging modality is unclear. Recently, SBRT has been shown to be both safe and effective when used in pts with locally advanced HCC. We prospectively compare SBRT to TACE as a bridge for HCC pts undergoing LT. Methods: 60 pts planned for accrual. From 9/2014-9/2016, 29 pts within Milan Criteria with C-P Class A/B cirrhosis were randomized to TACE vs. SBRT. TACE pts received 2 treatments one month apart utilizing DEBDOX beads (n = 15). TACE pts were hospitalized after each TACE. Pts receiving SBRT (n = 12) received a median total dose of 45Gy delivered over 5 fractions using fiducials. Mean liver dose, Veff, and NTCP were utilized to determine the prescription dose. Pts were assessed by imaging using mRECIST criteria at 2 months and every 3 months thereafter until LT or death. Toxicity and quality of life were assessed before treatment, during treatment, two weeks post-treatment, and then every three months using the PIQ-6 Pain Impact Questionnaire and the SF-36v2 Health Survey. Primary endpoint was time to retreatment of treated lesion(s). Secondary endpoints include toxicity, pathologic response, radiologic response, number of subsequent treatments, cost, and QOL. Results: A. Demographics/Toxicity. Conclusions: For HCC patients with C-P Class A/B liver cirrhosis, SBRT appears equally effective to TACE as a bridge to liver transplantation, may engender less toxicity, and eliminates hospitalizations. Clinical trial information: NCT02182687. [Table: see text][Table: see text]

Patient reported outcomes following palliative gastric RadiOtherapy for symptomatic advanced gastric cancer (PROG): Results from a phase 2 trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21667-e21667
Author(s):  
Jeremy Chee Seong Tey ◽  
Huili Zheng ◽  
Yu Yang Soon ◽  
Wee Yao Koh ◽  
Cheng Nang Leong ◽  
...  
Keyword(s):  
Patient Reported Outcomes ◽  
Locally Advanced ◽  
Significant Proportion ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Phase 2 Trial ◽  
Pain Subscale ◽  
Patient Reported ◽  
The Mean ◽  
Clinical Trial Information

e21667 Background: To determine the effect of gastric radiotherapy (RT) on patient reported outcomes (PROs; secondary endpoint) in the PROG trial. Methods: Patients with symptomatic locally advanced or metastatic gastric carcinoma with at least one index symptom of bleeding, pain or obstruction were treated with palliative gastric radiotherapy to a dose of 36Gy in 12 fractions (at 3Gy daily fractions). PROs were assessed using the European Organisation for Research and Treatment of Cancer Qualify of Life Questionanaire-C30 and stomach module STO22. The primary PRO hypothesis was that at least 30% of patients will achieve a > 10 point absolute improvement (considered significant) in the fatigue, nausea/vomiting and pain subscales in the C30, and dysphagia and pain subscales in the STO22 at 12 fractions and one month after radiotherapy. Assessments were performed at baseline, 12 fractions and one month post radiotherapy. Paired T test was used to compare the mean scores from baseline, and at 12 fractions and one month post completion of RT Results: Questionnaires were available from 49 of 50 patients (98%) at baseline, 36 of 45 patients (80%) at 12 fractions and 16 of 38 patients (42%) at one-month post RT. At 12 fractions, 50%, 28% and 44% of patients achieved a significant improvement in fatigue, nausea/vomiting and pain subscales in the C30 respectively. 42% and 28% of patients achieved a significant improvement in dysphagia and pain subscale in the STO22. The observed mean difference was 11 points and 4 points for pain subscale in the C30 and STO22 (P < 0.02). At one-month post RT, 63%, 31% and 50% of patients achieved a significant improvement in fatigue, nausea/vomiting and pain subscales in the C30 respectively. 44% and 19% of patients achieved a significant improvement in dysphagia and pain subscale in the STO22. There were no significant differences in the mean scores in the subscales of interest. Conclusions: Palliative gastric radiotherapy resulted in improvements in fatigue, dysphagia and pain at 12 fractions and at 1-month post radiotherapy in a significant proportion of patients. A phase III trial comparing the effects of different fractionation regimens on PROs is warranted. Clinical trial information: NCT01341756.

A phase Ib study of safety and clinical activity of atezolizumab (A) and cobimetinib (C) in patients (pts) with metastatic colorectal cancer (mCRC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 560-560 ◽  
Author(s):  
Johanna C. Bendell ◽  
Yung-Jue Bang ◽  
Cheng Ean Chee ◽  
David P. Ryan ◽  
Autumn Jackson McRee ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Clinical Activity ◽  
Immune Biomarkers ◽  
Primary Endpoints ◽  
Cell Accumulation ◽  
Molecular Determinants ◽  
Immune Therapies ◽  
Heavily Pretreated ◽  
Secondary Endpoints

560 Background: The majority of pts with mCRC have microsatellite stable (MSS) tumors with minimal response to PD-L1/PD-1 blockade. MEK inhibition upregulates tumor major histocompatibility complex-I expression, promotes intratumoral T-cell accumulation and improves anti–PD-L1 responses (Ebert, Immunity. 2016), supporting clinical evaluation of combined anti–PD-L1 (A) plus MEKi (C) in pts with mCRC. Methods: Pts with chemotherapy-refractory or locally advanced mCRC were evaluated. A was administered IV q2w at 800 mg. C was dosed PO daily at 20 to 60 mg during dose escalation and 60 mg during dose expansion (14/14 or 21/7 d on/off schedule). Primary endpoints were safety and tolerability. Investigator-assessed ORR and PFS by RECIST v1.1 and OS were secondary endpoints. Microsatellite instability (MSI) status was locally reported and centrally confirmed by NGS-based scoring. Results: As of May 10, 2017, 84 pts (57 KRASmt, 25 KRASwt, 2 unknown) were enrolled and evaluable. 66 pts had received 5+ prior therapies; 38 had known MSI status at baseline (MSS [n = 29], MSI-low [n = 8], MSI-H [n = 1]). A + C combination was tolerable. Treatment-related Gr 1-2 and Gr 3-4 AEs occurred at 60% and 37%, respectively. The most frequent related Gr 3-4 AEs were increased blood CPK, rash, diarrhea and fatigue (5% each). No treatment-related Gr 5 AEs occurred. 13% and 24% of pts experienced AEs leading to A and C withdrawal, respectively. Median follow-up was 14.3 mo (range, 0.5-29.8). Confirmed PR was observed in 7 pts (8%; locally reported MSS [n = 3], MSI-low [n = 1], MSI unknown [n = 3]). Median DOR was 14.8 mo (95% CI: 6.0, NE); DCR (PR + SD) was 31%. Median PFS was 1.9 mo (95% CI: 1.8, 2.3); median OS was 10.0 mo (95% CI: 6.2, 14.1). The 6-mo and 1-y OS rates were 65% (95% CI: 54, 76) and 46% (95% CI: 34, 58), respectively. Molecular determinants and immune biomarkers of response will be presented. Conclusions: A + C demonstrated a tolerable safety profile and improvements in OS vs those reported with SOC in heavily pretreated pts with mCRC. Objective responses observed in pts with MSS/MSI-low mCRC were durable, suggesting benefit of this novel combination in a pt population refractory to immune therapies. Clinical trial information: NCT01988896.

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