Rilpivirine plus cobicistat-boosted darunavir as alternative to standard three-drug therapy in HIV-infected, virologically suppressed subjects: Final results of the PROBE 2 trial

2021 ◽  
pp. 135965352110422
Author(s):  
Franco Maggiolo ◽  
Nicola Gianotti ◽  
Laura Comi ◽  
Elisa Di Filippo ◽  
Laura Fumagalli ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Virological Failure ◽  
Safety Data ◽  
Low Frequency ◽  
Integrase Inhibitor ◽  
Transcriptase Inhibitor ◽  
Primary Analysis ◽  
Open Label ◽  
Hiv Rna ◽  
Switch Group

Background Primary analysis at 24 weeks showed that switching to rilpivirine plus darunavir/cobicistat was non-inferior to continuing a standard three-drug antiretroviral regimen in virologically suppressed people with HIV. We present efficacy and safety data from the 48-week analysis. Methods PROBE 2 is a randomized, open-label trial. Adults who were on a three-drug therapy and had had <50 HIV-1 RNA copies/mL for at least 6 months were randomly assigned (1:1) to 25 mg rilpivirine plus 800/150 darunavir/cobicistat once daily (early switch group) or to continue their regimen for 24 weeks before switching (late switch group). In the 48-week analysis, the efficacy endpoint was the proportion of participants with <50 copies/mL of HIV-RNA (US Food and Drug Administration snapshot algorithm). The trial is registered with ClinicalTrials.gov , number NCT04064632. Findings 160 participants were recruited and randomized. At week 48, 70 (87.5%) in the early switch group and 76 (94.8%) in the late switch group maintained HIV-RNA <50 copies/mL. Virological failure (≥50 HIV-RNA copies/mL) was not seen in any patient of the early switch group and in 2 subjects in the late switch group none of which had treatment emergent resistance-associated mutation. Adverse events leading to treatment discontinuation occurred in 7 (8.7%) participants in the early switch group and in none in the late switch group. Interpretation The combination of rilpivirine plus darunavir/cobicistat sustained virological suppression, was associated with a low frequency of virological failure, and had a favorable safety profile, which support its use as a nucleoside reverse transcriptase inhibitor-sparing and integrase inhibitor-sparing alternative to three-drug regimens.

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): Final results from a phase 2, multicenter, open-label study (DESTINY-CRC01).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3505-3505
Author(s):  
Takayuki Yoshino ◽  
Maria Di Bartolomeo ◽  
Kanwal Pratap Singh Raghav ◽  
Toshiki Masuishi ◽  
Fotios Loupakis ◽  
...  
Keyword(s):  
Safety Profile ◽  
Topoisomerase I ◽  
Objective Response ◽  
Safety Data ◽  
Progression Free Survival ◽  
Drug Discontinuation ◽  
Phase 2 ◽  
Antibody Drug Conjugate ◽  
Primary Analysis ◽  
Open Label

3505 Background: T-DXd is an antibody–drug conjugate of a humanized anti-HER2 antibody bound to a topoisomerase I inhibitor by a cleavable linker. The primary analysis of DESTINY-CRC01 (DS8201-A-J203; NCT03384940), a phase 2, open-label, multicenter study of T-DXd in pts with HER2-expressing mCRC showed promising antitumor activity and a manageable safety profile (cohort A median follow-up [FU], 27.1 weeks; Siena S, ASCO 2020). We present updated longer-term efficacy and safety data. Methods: Pts had centrally confirmed HER2-expressing, RAS wild-type mCRC that progressed after ≥2 prior regimens. 6.4 mg/kg of T-DXd was administered every 3 weeks (Q3W) in 3 cohorts (A: HER2 IHC3+ or IHC2+/ISH+; B: IHC2+/ISH−; C: IHC1+). The primary end point was confirmed objective response rate (ORR) by independent central review in cohort A. Secondary end points were disease control rate (DCR; CR + PR + SD), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: At data cutoff (Dec 28, 2020), 86 pts (A, 53; B, 15; C, 18) received T-DXd. Median age was 58.5 y (range, 27-79), 53.5% were male, and 90.7% had left colon or rectum cancer. Median prior regimens for metastatic disease was 4 (range, 2-11). All pts had prior irinotecan; 30.2% in cohort A had prior anti-HER2 therapy. Median (m) treatment duration (all pts) was 3.0 mo (95% CI, 2.1-4.1; cohort A, 5.1 mo [95% CI, 3.9-7.6]). In cohort A (median FU, 62.4 weeks), confirmed ORR was 45.3% (24/53 pts; 95% CI, 31.6-59.6), DCR was 83.0% (44/53 pts; 95% CI, 70.2-91.9), mDOR was 7.0 mo (95% CI, 5.8-9.5), mPFS was 6.9 mo (95% CI, 4.1-8.7) with 37 (69.8%) PFS events, and mOS was 15.5 mo (95% CI, 8.8-20.8) with 36 (67.9%) OS events. These results are consistent with the primary analysis. Confirmed ORR was 43.8% (7/16 pts; 95% CI, 19.8-70.1) in pts with prior anti-HER2 therapy, 57.5% (23/40 pts; 95% CI, 40.9-73.0) in pts with IHC3+ status, and 7.7% (1/13 pts; 95% CI, 0.2-36.0) in pts with IHC2+/ISH+ status. In cohorts B and C, mPFS was 2.1 mo (95% CI, 1.4-4.1) and 1.4 mo (95% CI, 1.3-2.1); mOS was 7.3 mo (95% CI, 3.0-NE) and 7.7 mo (95% CI, 2.2-13.9), respectively. Treatment-emergent adverse events (TEAEs) of grade (G) ≥3 occurred in 65.1% of pts (56/86); the most common TEAEs were hematologic and gastrointestinal. TEAEs leading to drug discontinuation occurred in 13 pts (15.1%). 8 pts (9.3%) had interstitial lung disease (ILD) adjudicated by an independent committee as related to T-DXd (4 G2; 1 G3; 3 G5). Conclusions: T-DXd at 6.4 mg/kg Q3W showed promising activity and durability with longer-term FU in this pt population. The safety profile was consistent with prior results; ILD continues to be recognized as an important identified risk that requires careful monitoring and intervention as needed. These results support continued exploration of T-DXd in pts with HER2-overexpressing mCRC. Clinical trial information: NCT03384940.

scholarly journals Safety and Efficacy of Dolutegravir Plus Rilpivirine in Treatment-Experienced HIV-Infected Patients: The DORIVIR Study

2018 ◽  
Vol 17 ◽  
pp. 232595821876084 ◽  
Author(s):  
Rosario Palacios ◽  
M. Mayorga ◽  
C. M. González-Domenech ◽  
C. Hidalgo-Tenorio ◽  
C. Gálvez ◽  
...  
Keyword(s):  
Adverse Events ◽  
Hdl Cholesterol ◽  
Transcriptase Inhibitor ◽  
Strand Transfer ◽  
Open Label ◽  
Intention To Treat ◽  
Hiv Rna ◽  
Prior Art ◽  
Transfer Inhibitor ◽  
Reverse Transcriptase Inhibitor

Objectives: To analyze the efficacy and safety of dolutegravir/rilpivirine (DTG/RPV) in HIV-infected patients who switched from any other antiretroviral therapy (ART). Methods: Open-label, multicenter study including patients who switched to DTG/RPV between February 2015 and February 2016. Efficacy (HIV RNA <50 copies/mL), adverse events, and metabolic changes at 24 weeks were analyzed. Results: A total of 104 participants were included, who switched for the following reasons: toxicity/intolerance (42.3%), convenience (27.8%), and drug interactions (17.3%). Prior regimens are protease inhibitor (56.7%), integrase strand transfer inhibitor (26.9%), and non-nucleoside reverse transcriptase inhibitor (16.3%). Efficacy at 24 weeks was 88.4% (intention to treat) and 96.8% (per protocol). Triglyceride levels were reduced, on average, by 12.7% and a mean decrease of 9.0% in the glomerular filtration rate was observed as well ( P values of .003 and .002, respectively), whereas total cholesterol, HDL cholesterol, LDL cholesterol, creatinine, and glutamic-pyruvic transaminase remained unchanged. No patient discontinued due to adverse events. Conclusions: Dolutegravir/RPV is effective and safe in long-term HIV-infected patients under any prior ART. Toxicity, convenience, and interactions were the main reasons for changing. At 24 weeks, the lipid profile improved with a decrease in triglycerides.

scholarly journals Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study

2016 ◽  
Vol 76 (2) ◽  
pp. 355-363 ◽  
Author(s):  
Dae Hyun Yoo ◽  
Nenad Prodanovic ◽  
Janusz Jaworski ◽  
Pedro Miranda ◽  
Edgar Ramiterre ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Safety Data ◽  
Extension Study ◽  
Comparable Efficacy ◽  
Efficacy And Safety ◽  
Open Label ◽  
Acr20 Response ◽  
American College Of Rheumatology ◽  
Switch Group ◽  
Maintenance Group

ObjectivesTo assess the efficacy and safety of switching from the infliximab reference product (RP; Remicade) to its biosimilar CT-P13 (Remsima, Inflectra) or continuing CT-P13 in patients with rheumatoid arthritis (RA) for an additional six infusions.MethodsThis open-label extension study recruited patients with RA who had completed the 54-week, randomised, parallel-group study comparing CT-P13 with RP (PLANETRA; NCT01217086). CT-P13 (3 mg/kg) was administered intravenously every 8 weeks from weeks 62 to 102. All patients received concomitant methotrexate. Endpoints included American College of Rheumatology 20% (ACR20) response, ACR50, ACR70, immunogenicity and safety. Data were analysed for patients who received CT-P13 for 102 weeks (maintenance group) and for those who received RP for 54 weeks and then switched to CT-P13 (switch group).ResultsOverall, 302 of 455 patients who completed the PLANETRA study enrolled into the extension. Of these, 158 had received CT-P13 (maintenance group) and 144 RP (switch group). Response rates at week 102 for maintenance versus switch groups, respectively, were 71.7% vs 71.8% for ACR20, 48.0% vs 51.4% for ACR50 and 24.3% vs 26.1% for ACR70. The proportion of patients with antidrug antibodies was comparable between groups (week 102: 40.3% vs 44.8%, respectively). Treatment-emergent adverse events occurred in similar proportions of patients in the two groups during the extension study (53.5% and 53.8%, respectively).ConclusionsComparable efficacy and tolerability were observed in patients who switched from RP to its biosimilar CT-P13 for an additional year and in those who had long-term CT-P13 treatment for 2 years.Trial registration numberNCT01571219; Results.

scholarly journals Pharmacokinetic Effects of Coadministration of Lersivirine with Raltegravir or Maraviroc in Healthy Subjects

2011 ◽  
Vol 56 (2) ◽  
pp. 887-892 ◽  
Author(s):  
Manoli Vourvahis ◽  
Grant Langdon ◽  
Robert R. LaBadie ◽  
Gary Layton ◽  
Marie-Noella Ndongo ◽  
...  
Keyword(s):  
Steady State ◽  
Integrase Inhibitor ◽  
Transcriptase Inhibitor ◽  
Time Profile ◽  
Maximum Plasma ◽  
Open Label ◽  
Nonnucleoside Reverse Transcriptase Inhibitor ◽  
Cyp3a4 Enzyme ◽  
Reverse Transcriptase Inhibitor ◽  
Drug Resistant Strains

ABSTRACTLersivirine (UK-453,061) is a new nonnucleoside reverse transcriptase inhibitor currently being developed as a treatment for human immunodeficiency virus type 1 infection. Lersivirine shows potent activity against wild-type and clinically relevant drug-resistant strains. Previous studies have demonstrated that lersivirine is metabolized by glucuronidation via UGT2B7 and by cytochrome P450 3A4 (CYP3A4). Lersivirine is also a weak inducer of the CYP3A4 enzyme. Therefore, coadministered lersivirine could potentially affect the pharmacokinetics of maraviroc, a CCR5 antagonist metabolized by CYP3A4, and raltegravir, an integrase inhibitor metabolized by glucuronidation. Two open-label studies assessed the pharmacokinetics of raltegravir and of maraviroc when they were coadministered with lersivirine and the pharmacokinetics of lersivirine when it was coadministered with raltegravir. Minor, clinically nonsignificant effects on the pharmacokinetics of raltegravir coadministered with lersivirine were observed at steady state for raltegravir, with estimated mean changes of −15%, −29%, and +25% in the area under the concentration-time profile from time zero to the end of the dosing interval (AUCtau), maximum plasma concentration (Cmax), and concentration observed 12 h postdose (C12), respectively. There were no clinically relevant effects of steady-state raltegravir on lersivirine AUCtau,Cmax, or concentration observed 24 h postdose (C24) (estimated mean changes of −2 to +5%). Coadministration of lersivirine at steady state with maraviroc resulted in no clinically relevant effects on maraviroc AUCtau,Cmax, orC12(estimated mean changes of +3.4 to +8.6%). Lersivirine appeared to be generally well tolerated in these studies and appears to be suitable for coadministration with raltegravir or maraviroc without the need for dose modification.

scholarly journals LGG-49. SAFETY AND EFFICACY OF TRAMETINIB (T) MONOTHERAPY AND DABRAFENIB + TRAMETINIB (D+T) COMBINATION THERAPY IN PEDIATRIC PATIENTS WITH BRAF V600-MUTANT LOW-GRADE GLIOMA (LGG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii375-iii375
Author(s):  
Eric Bouffet ◽  
James A Whitlock ◽  
Christopher Moertel ◽  
Birgit Geoerger ◽  
Isabelle Aerts ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Pediatric Patients ◽  
Objective Response ◽  
Safety Data ◽  
Dose Finding ◽  
Combination Group ◽  
Clinical Activity ◽  
Low Grade ◽  
Open Label ◽  
Independent Review

Abstract BACKGROUND Children with BRAF V600-mutant LGG have suboptimal response to standard chemotherapy. Previously, D (BRAF V600 inhibitor) monotherapy has demonstrated clinical benefit in this population. We report interim analysis results of pediatric patients with recurrent/refractory BRAF V600-mutant LGG treated with either T (MEK1/2 inhibitor) monotherapy or D+T combination therapy. METHODS This is a 4-part, open-label, multicenter, phase I/II study (NCT02124772) in pediatric patients (&lt;18 y) with refractory/recurrent tumors. The dose-finding phase, including dose confirmation stratified by age, was followed by disease-specific cohorts at recommended dose levels. Efficacy was determined by both investigator and independent review using RANO criteria. Adverse events (AEs) were assessed per NCI-CTCAE v4.03. RESULTS Of 49 pediatric patients with BRAF V600-mutant LGG (T, n=13; D+T, n=36) enrolled, pooled efficacy data was available for both treatments while safety data was available for 30 patients (T, n=10; D+T, n=20). Most patients (n=8/10) receiving T monotherapy withdrew/discontinued the treatment in contrast to 3/20 in the D+T group. Pyrexia occurred in 50% of patients (n=5/10) in the monotherapy group and was a frequent AE in the combination group (75%; n=15/20). Objective response rate per independent review was 15% (95% CI, 2%–45%) with T monotherapy and 25% (95% CI, 12%–42%) with D+T combination therapy. Seven patients (54%) on monotherapy and 33 patients (92%) on combination therapy had stable disease or better. CONCLUSION In pediatric patients with previously treated BRAF V600-mutant LGG, T monotherapy and D+T combination therapy demonstrated clinical activity, with pyrexia being a common AE.

scholarly journals Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate)

2017 ◽  
Vol 77 (2) ◽  
pp. 212-220 ◽  
Author(s):  
Dinesh Khanna ◽  
Christopher P Denton ◽  
Celia J F Lin ◽  
Jacob M van Laar ◽  
Tracy M Frech ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Phase Ii ◽  
Controlled Trial ◽  
Safety Data ◽  
Open Label ◽  
Double Blind ◽  
Skin Score ◽  
Open Label Extension ◽  
Registration Number ◽  
Randomised Controlled

ObjectivesAssess the efficacy and safety of tocilizumab in patients with systemic sclerosis (SSc) in a phase II study.MethodsPatients with SSc were treated for 48 weeks in an open-label extension phase of the faSScinate study with weekly 162 mg subcutaneous tocilizumab. Exploratory end points included modified Rodnan Skin Score (mRSS) and per cent predicted forced vital capacity (%pFVC) through week 96.ResultsOverall, 24/44 (55%) placebo-tocilizumab and 27/43 (63%) continuous-tocilizumab patients completed week 96. Observed mean (SD (95% CI)) change from baseline in mRSS was –3.1 (6.3 (–5.4 to –0.9)) for placebo and –5.6 (9.1 (–8.9 to–2.4)) for tocilizumab at week 48 and –9.4 (5.6 (–8.9 to –2.4)) for placebo-tocilizumab and –9.1 (8.7 (–12.5 to –5.6)) for continuous-tocilizumab at week 96. Of patients who completed week 96, any decline in %pFVC was observed for 10/24 (42% (95% CI 22% to 63%)) placebo-tocilizumab and 12/26 (46% (95% CI 27% to 67%)) continuous-tocilizumab patients in the open-label period; no patients had >10% absolute decline in %pFVC. Serious infection rates/100 patient-years (95% CI) were 10.9 (3.0 to 27.9) with placebo and 34.8 (18.0 to 60.8) with tocilizumab during the double-blind period by week 48 and 19.6 (7.2 to 42.7) with placebo-tocilizumab and 0.0 (0.0 to 12.2) with continuous-tocilizumab during the open-label period.ConclusionsSkin score improvement and FVC stabilisation in the double-blind period were observed in placebo-treated patients who transitioned to tocilizumab and were maintained in the open-label period. Safety data indicated increased serious infections in patients with SSc but no new safety signals with tocilizumab.Trial registration numberNCT01532869; Results.

Participants on dolutegravir re-suppress HIV RNA after virologic failure: updated data from the ADVANCE trial

2021 ◽  
Author(s):  
Toby Pepperrell ◽  
Willem Daniel Francois Venter ◽  
Kaitlyn McCann ◽  
Bronwyn Bosch ◽  
Melissa Tibbatts ◽  
...  
Keyword(s):  
Virological Failure ◽  
Virologic Failure ◽  
Hiv Rna ◽  
Suppressive Capacity

Abstract Following evidence of HIV RNA re-suppression on DTG-based regimens, we assess the re-suppressive capacity of ADVANCE participants on TAF/FTC+DTG, TDF/FTC+DTG and TDF/FTC/EFV. Viraemic participants were able to re-suppress within 3 follow-up visits of protocol-defined virological failure (PDVF) in 77/121(64%), 85/126(67%) and 44/138(32%) cases respectively (DTG regimens vs. TDF/FTC/EFV; p&lt;0.001).

Atezolizumab + obinutuzumab + venetoclax in patients with relapsed or refractory indolent non-Hodgkin’s lymphoma (R/R iNHL): Primary analysis of a phase 2 trial from LYSA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7544-7544
Author(s):  
Charles Herbaux ◽  
Herve Ghesquieres ◽  
Reda Bouabdallah ◽  
Stephanie Guidez ◽  
Emmanuel Gyan ◽  
...  
Keyword(s):  
Tumor Lysis Syndrome ◽  
Safety Data ◽  
Induction Treatment ◽  
Phase 2 ◽  
Primary Analysis ◽  
Phase 2 Trial ◽  
Ann Arbor ◽  
Baseline Characteristics ◽  
Grade 3

7544 Background: R/R iNHL treatment remains challenging. Atezolizumab (ATE) and obinutuzumab (OBI) are monoclonal antibodies acting respectively to inhibit T-lymphocyte exhaustion or by inducing lymphoma cells cytotoxicity, whereas venetoclax (VEN) is a small molecule inhibiting BCL-2. Combining tumor-targeted therapies with agents that enhance anti-tumor immunity represents an attractive treatment paradigm. This LYSA sponsored multicenter phase 2 trial (NCT03276468) evaluated ATE, OBI and VEN combination in R/R B-cell lymphomas. Herein, we present primary efficacy and safety data from the iNHL cohort including Follicular Lymphoma (FL) and Marginal Zone Lymphomas (MZL). Methods: Patients ≥18 years with biopsy-confirmed R/R FL and MZL who failed at least one line of therapy were eligible. OBI was given IV at 1 g on day (D) 1, 8 and 15 of cycle (C) 1 and on D1 from C2 to C8 every 3 weeks. ATE was given IV, 1.2 g every 3 weeks, started at D2 of C1, then administered at D2 of each cycle for 24 cycles. VEN was given orally at 800 mg/D at full dose, starting on D8C1 for 24 cycles. The primary endpoint was the Overall Response Rate (ORR) evaluated by Lugano criteria at the end of induction (EOI) after 8 cycles of ATE, OBI and VEN (M6) or at premature treatment discontinuation. Results: At the time of the primary analysis (08 Jan 2021), 78 patients were enrolled. FL cohort (n = 58): the median follow-up was 14.5 months. Main baseline characteristics were: Ann Arbor Stage III/IV, 85.7%; FLIPI HR, 47.3%; > 2 prior lines of therapy, 32.1%; and exposed to ASCT, 30.4%. The ORR on PET scan at EOI was measured at 53.6% [41.8%-65.1%], including 30.4% of CMR. 37 patients (63%) received the full induction treatment. MZL cohort (n = 20; 13 nMZL, 5 eMZL, 2 sMZL): the median follow-up was 11.9 months. Main baseline characteristics were: Ann Arbor Stage IV, 100%; bone marrow infiltration, 38.9%; ≥ 2 extra-nodal sites, 50%; and > 2 prior lines of therapy, 22.2%. The ORR on CT scan at EOI was measured at 66.76% [44.6%-84.4%], including 16.7% of CR and 50.0% PR. 11 patients (55%) received the full induction treatment. At time of the present analysis, responses in the 2 cohorts seem durable with only 21,4% of responders who have reported relapse/progression. Out of the 78 pts, a total of 55 (70.5%) pts experienced grade 3–4 adverse event (AE) and 1 patient experienced an AE that led to discontinuation of any drug. Main AE of grade 3 or more were hematologic cytopenias, with only one febrile neutropenia (1.3%). Three pts experienced immune-related AE (1 grade 2 myositis and 2 grade 3 colitis), no tumor lysis syndrome was observed. Conclusions: ATE, OBI and VEN triplet appears to be well tolerated, with no unexpected toxicity brought by the combination. The ORR at EOI seems to be comparable to other innovative regiments in this setting, with durable responses to date. Clinical trial information: NCT03276468.

Obinutuzumab short-duration infusion (SDI) in previously untreated advanced follicular lymphoma: Results from the end of induction analysis of the phase IV GAZELLE study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7545-7545
Author(s):  
Miguel Angel A. Canales Albendea ◽  
Thomas A. Buchholz ◽  
Koji Izutsu ◽  
Takayuki Ishikawa ◽  
Laura Maria Fogliatto ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Complete Response ◽  
Primary Analysis ◽  
Open Label ◽  
Secondary Endpoints ◽  
To Receive ◽  
Phase Iv

7545 Background: Obinutuzumab (G)-chemotherapy (chemo) has demonstrated improved progression-free survival compared with rituximab (R)-chemo in previously untreated advanced follicular lymphoma (FL). G is currently administered by IV infusion over ̃3–4 hours. A shorter duration of infusion in Cycle (C) 2 and subsequent cycles, as is standard practice with R, could improve convenience for patients (pts) and efficiency for infusion facilities. We report the primary analysis of the prospective, open-label, multicenter, single-arm, Phase IV, GAZELLE study (NCT03817853), which evaluated the safety of G administered as a 90-minute (min) SDI from C2 onwards in pts with FL. Methods: Pts with previously untreated FL received G (1000mg) intravenously on Day (D) 1, 8, and 15 of C1, and on D1 thereafter, plus chemo (bendamustine, CHOP, or CVP) for 6–8 cycles. In C1, pts received G at the standard infusion rate. Pts without a Grade (Gr) ≥3 infusion-related reaction (IRR) in C1 were eligible to receive G as a 90-min SDI from C2. Pts with a Gr 3 IRR in C1 received the standard G infusion in C2, and were eligible for G SDI in subsequent cycles if no Gr ≥3 IRRs occurred. Pts with a second Gr 3/4 IRR discontinued G. At the end of induction (EOI), responding pts received maintenance G (1000mg) as SDI for 2 years or until disease progression (PD). The primary endpoint was incidence of Gr ≥3 IRRs during C2. IRRs were defined as any event occurring ≤24 hours from infusion judged to be related to treatment. Secondary endpoints included adverse events (AEs) and investigator-assessed overall response rate at EOI. Results: As of December 3, 2020, 113 pts had received study treatment. Median age was 62.0 years, 50.4% were male, 61.9% had stage IV FL, and 45.1% were classified as high-risk FLIPI. Of the 110 pts who were eligible for G SDI from C2, no pt experienced a Gr ≥3 IRR with SDI in C2 (Table). One pt experienced a Gr 3 IRR with SDI in C5, presenting hypertension. All other IRRs with SDI were Gr 1/2. No Gr 4/5 IRRs were reported. Other AEs were similar to those observed in previous studies. At the clinical cut-off date, 104 pts had a CT imaging-based response assessment at EOI and 9 pts had no response assessment; 76/113 (67.3%) had a complete response, 22 (19.5%) had a partial response, and six (5.8%) had PD. Conclusions: In GAZELLE, G SDI in C2 and beyond appeared to be safe. No Gr 3 IRRs were observed in C2 and only one Gr 3 IRR was reported in subsequent cycles. The safety profile of G SDI was comparable with the established profile of G in advanced FL. Clinical trial information: NCT03817853. [Table: see text]

Health-related quality of life (HRQOL) in patients (pts) with advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC) or esophageal adenocarcinoma (EAC): Results of nivolumab plus chemotherapy (NIVO+chemo) versus chemo from CheckMate 649.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 167-167
Author(s):  
Elena Elimova ◽  
Lucjan Wyrwicz ◽  
Steven I. Blum ◽  
Hong Xiao ◽  
Mingshun Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastroesophageal Junction ◽  
Well Being ◽  
Primary Analysis ◽  
Open Label ◽  
Cox Models ◽  
Study Objective ◽  
Gastroesophageal Junction Cancer ◽  
Patient Reported ◽  
Mean Differences

167 Background: CheckMate 649 (NCT02872116) is a randomized, open label phase 3 study in first line (1L) treatment of pts with advanced GC/GEJC/EAC. Primary analysis results showed statistically significant improvement in overall survival (OS) for NIVO+chemo vs. chemo in all randomized pts. We present HRQOL results for these pts, included as an exploratory study objective. Methods: HRQOL was assessed using EQ-5D-3L (EQ-5D) and Functional Assessment of Cancer Therapy–Gastric Cancer (FACT-Ga). Assessments were performed at baseline (BL), every 6 weeks during treatment and during follow-up. Change from BL EQ-5D Visual Analog Scale (VAS), Utility Index (UI) and FACT-Ga scores were analyzed using mixed models. Time to first symptom deterioration (TTSD), time until definitive deterioration (TuDD), and time to improvement (TTI) were estimated with Kaplan-Meier estimators and stratified Cox models; deterioration/improvement was based on prespecified meaningful change thresholds. Results: 1581 pts were randomized to NIVO+chemo (n = 789) or chemo (n = 792). Among 1359 pts with BL and post-BL patient-reported outcomes (NIVO+chemo, n = 693; chemo, n = 666), BL scores for FACT-Ga total were similar between treatment groups. Least squares mean differences from BL favored NIVO+chemo at most visits for EQ-5D, FACT-Ga total, and Gastric Cancer Subscale (GaCS), and were comparable for other subscales (not shown). TTI generally favored NIVO+chemo (most HR > 1) but was not significantly different between arms. TTSD was longer in NIVO+chemo arm compared with chemo alone (all HRs < 1), except for Emotional Well-Being (WB); only GaCS and FACT-Ga total were significantly different between arms. TuDD showed statistically significant delays in deterioration (HR with CI < 1) for all scores expect Social WB. Conclusions: Compared with chemo alone, the addition of NIVO to chemo maintained HRQoL with a decreased risk of symptom deterioration in patients with previously untreated advanced or metastatic GC/GEJC/EAC. Together with improved OS, these data support NIVO+chemo as a new 1L standard treatment for GC/GEJC/EAC. Clinical trial information: NCT02872116. [Table: see text]

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