The anti–PD-1 antibody spartalizumab in combination with dabrafenib and trametinib in advanced BRAF V600–mutant melanoma: Efficacy and safety findings from parts 1 and 2 of the Phase III COMBI-i trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10028-10028 ◽  
Author(s):  
Georgina V. Long ◽  
Celeste Lebbe ◽  
Victoria Atkinson ◽  
Mario Mandalà ◽  
Paul D. Nathan ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Safety Data ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Grade 3 ◽  
The Impact

10028 Background: Treatment (tx) with checkpoint inhibitors or targeted therapy improves outcomes in patients (pts) with BRAF V600–mutant advanced melanoma; however, many pts subsequently progress and die. Preliminary evidence suggests that targeted therapy may enhance the impact of checkpoint inhibitors and improve efficacy compared with either treatment alone. Methods: COMBI-i is investigating first-line spartalizumab 400 mg every 4 wk + dabrafenib 150 mg twice daily + trametinib 2 mg once daily in pts with unresectable or metastatic BRAF V600–mutant melanoma (NCT02967692). We report efficacy and safety data from parts 1 (run-in cohort) and 2 (biomarker cohort), with a median follow-up of 24.3 mo. Response was assessed per RECIST v1.1. The randomized part 3 is ongoing. Results: 36 pts were enrolled (part 1: n = 9; part 2: n = 27); 20 (56%) had stage IV M1c disease and 15 (42%) had elevated lactate dehydrogenase (LDH) levels (≥ upper limit of normal). At the data cutoff (August 19, 2019), tx was ongoing in 10 pts (28%). The confirmed investigator-assessed objective response rate (ORR) was 78% (n = 28), with 16 complete responses (CRs; 44%) and 12 partial responses (33%). Median duration of response (DOR; 10/28 responders with events) was not reached (NR); 24-mo DOR rate was 53.4% (95% CI, 29%-73%). Median progression-free survival (PFS) was 22.7 mo; 24-mo PFS rate was 41.4% (95% CI, 23%-59%). At the cutoff, median overall survival (OS) was NR, with a 24-mo OS rate of 74.1% (95% CI, 56%-86%). In pts with elevated LDH, ORR was 67%, with 4 CRs (27%); median PFS was 10.7 mo (95% CI, 4.6-19.1 mo), and median OS was NR. The estimated 24-mo PFS and OS rates in these pts were 26.7% and 52.5%, respectively. All pts had ≥ 1 tx-related adverse event (TRAEs); 26 (72%) had grade ≥ 3 TRAEs. The most common grade ≥ 3 TRAEs were pyrexia (17%), increased lipase (11%), neutropenia (11%), increased blood creatine phosphokinase (8%), and increased γ-glutamyltransferase (8%). AEs leading to discontinuation of all 3 study drugs occurred in 6 pts (17%). All-causality grade ≥ 3 AEs requiring immunosuppressive medication occurred in 19 pts (53%). One pt died of cardiac arrest that was not considered tx related. Conclusions: The combination of spartalizumab + dabrafenib + trametinib resulted in high ORR and CR rates, with a high frequency of durable responses, including in patients with poor prognostic factors. Clinical trial information: NCT02967692.

The anti–PD-1 antibody spartalizumab (S) in combination with dabrafenib (D) and trametinib (T) in previously untreated patients (pts) with advanced BRAF V600–mutant melanoma: Updated efficacy and safety from parts 1 and 2 of COMBI-i.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9531-9531 ◽  
Author(s):  
Georgina V. Long ◽  
Celeste Lebbe ◽  
Victoria Atkinson ◽  
Mario Mandalà ◽  
Paul D. Nathan ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Safety Data ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Antigen Expression ◽  
Synergistic Activity ◽  
Efficacy And Safety ◽  
Grade 3

9531 Background: Checkpoint inhibitors and targeted therapies have improved outcomes in pts with BRAF V600–mutant advanced melanoma; however, many pts progress and new treatment (tx) strategies are needed. BRAF inhibition increases T-cell infiltration, melanoma antigen expression, and PD-1/PD-L1 expression, which may lead to synergistic activity with anti–PD-1 therapy. Methods: COMBI-i is investigating first-line S 400 mg Q4W + D 150 mg BID + T 2 mg QD in pts with unresectable or metastatic BRAF V600–mutant melanoma (NCT02967692). Here we report pooled efficacy and safety data from parts 1 (run-in cohort) and 2 (biomarker cohort). Response was assessed per RECIST v1.1. Results: 36 pts were enrolled (part 1: n = 9; part 2: n = 27); 18 (50%) had stage IV M1c and 15 (42%) had elevated LDH levels. At the data cutoff (median follow-up, 15.2 mo), tx was ongoing in 17 pts (47%). The confirmed objective response rate (ORR) by investigator assessment was 75% (n = 27), with 33% complete responses (CRs; n = 12). Medians for duration of response (DOR; 7/27 pts with events), progression-free survival (PFS; 13/36 pts with events), and overall survival (OS; 7/36 pts with events) were not reached. 12-mo DOR rate was 71.4% (95% CI, 49%-85%). 12-mo PFS and OS rates were 65.3% (95% CI, 47%-79%) and 85.9% (95% CI, 69%-94%), respectively. In pts with high baseline LDH: ORR was 67%, with 3 CRs (20%), median PFS was 10.7 mo (events in 10/15 pts [67%]), and median OS was not reached, with events in 6/15 pts (40%). All pts had ≥ 1 AE; 27 (75%) had grade ≥ 3 AEs. 6 pts (17%) had AEs leading to discontinuation of all 3 study drugs. Any-grade AEs in ≥ 40% of pts included pyrexia, chills, fatigue, cough, and arthralgia. Grade ≥ 3 AEs in > 3 pts were neutropenia, pyrexia, and increased lipase. One pt died of cardiac arrest that was not considered related to study tx. Conclusions: S+D+T showed promising and durable ORR (75%) with CR in 33% of pts. With > 15 mo of follow-up, median PFS was not reached. The safety profile was manageable reflecting individual toxicities of D, T, and S. The global, placebo-controlled, randomized phase 3 (part 3) of COMBI-i is ongoing. Clinical trial information: NCT02967692.

The anti–PD-1 antibody spartalizumab (S) in combination with dabrafenib (D) and trametinib (T) in previously untreated patients (pts) with advanced BRAF V600–mutant melanoma: Updated efficacy and safety from parts 1 and 2 of COMBI-I.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 57-57 ◽  
Author(s):  
Georgina V. Long ◽  
Celeste Lebbe ◽  
Victoria Atkinson ◽  
Mario Mandalà ◽  
Paul D. Nathan ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Safety Data ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Antigen Expression ◽  
Synergistic Activity ◽  
Efficacy And Safety ◽  
Grade 3

57 Background: Checkpoint inhibitors and targeted therapies have improved outcomes in pts with BRAF V600–mutant advanced melanoma; however, many pts progress and new treatment (tx) strategies are needed. BRAF inhibition increases T-cell infiltration, melanoma antigen expression, and PD-1/PD-L1 expression, which may lead to synergistic activity with anti–PD-1 therapy. Methods: COMBI-i is investigating first-line S 400 mg Q4W + D 150 mg BID + T 2 mg QD in pts with unresectable or metastatic BRAF V600–mutant melanoma (NCT02967692). Here we report pooled efficacy and safety data from parts 1 (run-in cohort) and 2 (biomarker cohort). Response was assessed per RECIST v1.1. Results: 36 pts were enrolled (part 1: n = 9; part 2: n = 27); 18 (50%) had stage IV M1c and 15 (42%) had elevated LDH levels. At the data cutoff (median follow-up, 15.2 mo), tx was ongoing in 17 pts (47%). The confirmed objective response rate (ORR) by investigator assessment was 75% (n = 27), with 33% complete responses (CRs; n = 12). Medians for duration of response (DOR; 7/27 pts with events), progression-free survival (PFS; 13/36 pts with events), and overall survival (OS; 7/36 pts with events) were not reached. 12-mo DOR rate was 71.4% (95% CI, 49%-85%). 12-mo PFS and OS rates were 65.3% (95% CI, 47%-79%) and 85.9% (95% CI, 69%-94%), respectively. In pts with high baseline LDH: ORR was 67%, with 3 CRs (20%), median PFS was 10.7 mo (events in 10/15 pts [67%]), and median OS was not reached, with events in 6/15 pts (40%). All pts had ≥ 1 AE; 27 (75%) had grade ≥ 3 AEs. 6 pts (17%) had AEs leading to discontinuation of all 3 study drugs. Any-grade AEs in ≥ 40% of pts included pyrexia, chills, fatigue, cough, and arthralgia. Grade ≥ 3 AEs in > 3 pts were neutropenia, pyrexia, and increased lipase. One pt died of cardiac arrest that was not considered related to study tx. Conclusions: S+D+T showed promising and durable ORR (75%) with CR in 33% of pts. With > 15 mo of follow-up, median PFS was not reached. The safety profile was manageable reflecting individual toxicities of D, T, and S. The global, placebo-controlled, randomized phase 3 (part 3) of COMBI-i is ongoing. Clinical trial information: NCT02967692.

Efficacy and safety of first-line bevacizumab (Bv) and cisplatin/gemcitabine (CG) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC) in the BO17704 study (AVAiL)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8050-8050 ◽  
Author(s):  
N. B. Leighl ◽  
P. Zatloukal ◽  
J. Mezger ◽  
R. Ramlau ◽  
V. Archer ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Safety Data ◽  
Progression Free Survival ◽  
The Elderly ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Safety Signals

8050 Background: AVAiL, an international, placebo-controlled, phase III trial, evaluated Bv plus CG in pts with previously untreated advanced, non-squamous NSCLC, with performance status 0/1. A retrospective analysis was performed to assess the efficacy and safety of Bv plus CG in the subpopulation of elderly pts (≥65 years [yrs]). Methods: 1,043 pts (age 20–83) were randomized to C 80mg/m2 and G 1,250mg/m2 q3w for up to 6 cycles plus either Bv 7.5mg/kg q3w (Bv 7.5; n=345), Bv 15mg/kg q3w (Bv 15; n=351) or placebo (Pl; n=347). Bv/Pl was administered until disease progression. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (RR) and safety. Efficacy and safety were compared between pts <65 yrs vs ≥65 yrs. Results: Efficacy data were available for 304 pts ≥65 yrs (median age 68), and 739 pts <65 yrs (median age 55). Baseline characteristics were similar between the groups. In the Bv arms, 179 pts (93%) received ≥1 cycle of treatment; 85 (47.5%) completed >6 cycles. Bv-treated pts ≥65 yrs derived an improvement in PFS compared to Pl (Bv 7.5: HR 0.71, p 0.023; Bv 15: HR 0.84, p= 0.25). ORRs were 40%, 29% and 30% for pts ≥65 in the Bv 7.5, Bv 15 and Pl arms. Survival was similar in all treatment arms regardless of age, (pts ≥65 Bv 7.5 HR 0.84; Bv 15 HR 0.88, p=NS). Safety data were available for 284 pts ≥65 yrs and 702 pts <65 yrs. There were no safety signals of concern in older patients. Grade ≥3 toxicities occurred in 84%, 80% and 80% of older pts treated with Bv 7.5, Bv 15 and Pl. Pts ≥65 yrs had no episodes of severe hemoptysis, but in Bv 7.5 and Pl arms, were more likely to have other bleeding, compared to pts <65. The incidence of hypertension and febrile neutropenia were similar in pts ≥65 and <65 yrs. Treatment-related deaths were not increased in Bv-treated pts ≥65 yrs vs pts <65 yrs or in Bv-arms vs Pl. Conclusions: The PFS benefit from Bv-based treatment in the elderly subpopulation is similar to that observed in the overall patient population. No particular safety signals were identified in this population, suggesting acceptable tolerability of Bv in elderly pts in AVAiL. [Table: see text]

An international, randomized, placebo-controlled, double-blind phase III study (MONET1) of motesanib plus carboplatin/paclitaxel (C/P) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC).

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. LBA7512-LBA7512 ◽  
Author(s):  
G. Scagliotti ◽  
I. Vynnychenko ◽  
Y. Ichinose ◽  
K. Park ◽  
K. Kubota ◽  
...  
Keyword(s):  
Cox Model ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
High Rate ◽  
Phase Iii ◽  
Rank Test ◽  
Double Blind ◽  
Grade 3 ◽  
Nonsquamous Nsclc

LBA7512 Background: This study evaluated whether motesanib (a selective oral inhibitor of VEGFR 1, 2 and 3; PDGFR and Kit) plus C/P improved overall survival (OS) compared with placebo + C/P in patients (pts) with nonsquamous NSCLC and in a subset of pts with adenocarcinoma. Methods: Pts had stage IIIB/IV or recurrent nonsquamous NSCLC and no prior systemic therapy for advanced NSCLC. The study initially enrolled all histologies but was amended to exclude pts with squamous NSCLC owing to a high rate of hemoptysis. Pts were randomized 1:1 to receive up to six 3-wk cycles of C (AUC 6 mg/mL·min) and P (200 mg/m2) with either motesanib 125 mg QD (Arm A) or placebo QD (Arm B) orally continuously. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), adverse events (AEs), objective response rate (ORR) and association between placental growth factor (PLGF) change and OS. OS was evaluated using a stratified Cox model and 2-sided log-rank test (α=0.03 for nonsquamous pts and α=0.02 for adenocarcinoma pts). Results: 1090 pts with nonsquamous NSCLC were randomized (Arm A/B, n=541/549); 890 had adenocarcinoma (n=448/442). 61% were men; median age was 60 years (range 21–87); 83% had stage IV disease. At the time of analysis, 753 pts had died (608 pts with adenocarcinoma). Median follow-up was 10.6 mo. OS was not significantly improved in Arm A compared with Arm B (Table). In Arm A, PLGF analysis did not show an association with OS. The incidence of grade ≥3 AEs in Arms A/B was 73/59%. Grade ≥3 AEs occurring more frequently in Arm A than B included neutropenia (22/15%), diarrhea (9/1%), hypertension (7/1%) and cholecystitis (3/0%). The incidence of grade 5 AEs was 14/9% in Arms A/B. Conclusions: In pts with advanced nonsquamous NSCLC, treatment with motesanib + C/P did not significantly improve OS compared with C/P alone. [Table: see text]

Randomized, open-label, phase III study of pemetrexed plus carboplatin (PemC) followed by maintenance pemetrexed versus paclitaxel/carboplatin/bevacizumab (PCB) followed by maintenance bevacizumab in patients with advanced nonsquamous (NS) non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. LBA8003-LBA8003 ◽  
Author(s):  
Ralph Zinner ◽  
Helen J. Ross ◽  
Robert Weaver ◽  
Ramaswamy Govindan ◽  
Viran R. Holden ◽  
...  
Keyword(s):  
Safety Data ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Drug Regimen ◽  
Primary Objective ◽  
Phase Iii ◽  
Rank Test ◽  
Type I ◽  
Open Label ◽  
Grade 3

LBA8003 Background: PemC and PCB are regimens used for first-line treatment of advanced NS-NSCLC. The primary objective was to compare progression-free survival without Grade 4 toxicity (G4PFS) between two vs three drug regimen arms. Methods: Patients ≥18 years, Stage IV NS NSCLC, AJCC (v7.0), and ECOG PS 0/1 were enrolled. Patients were randomized (1:1); received 4 cycles of induction (PemC: Pem, 500 mg/m2 and C, AUC = 6; PCB: P, 200 mg/m2, C, AUC = 6, and B, 15 mg/kg) followed by Pem (PemC Arm) or B (PCB Arm) maintenance therapy in the absence of progressive disease or discontinuation. Secondary endpoints were PFS, overall survival (OS), overall response rate (ORR), and disease control rate (DCR). The study was powered for G4PFS; assuming hazard ratio (HR) of 0.75; there was 80% power to detect superiority of PemC over PCB with a 2-sided type I error of 0.10. Efficacy data were analyzed by intent-to-treat principle using the log-rank test for time-to-event variables, and an exact test for ORR and DCR. Safety data were evaluated using CTCAE v3 for patients who received ≥1 dose of study treatment. Results: Patients were randomized to PemC (N = 182) or PCB (N = 179). Baseline factors were balanced between arms: median age 66/66 years; % female 42/42; % PS=0, 47/47; % stage IV M1a 29/30; for PemC vs PCB, median G4PFS (months) was 3.91/2.86 (HR = 0.85, 90% CI 0.7, 1.04, p = 0.176); PFS and OS had HR = 1.06 (95% CI 0.84, 1.35), p = 0.610, and HR = 1.07 (95% CI 0.83, 1.36), p = 0.616, respectively. The ORR (%) 23.6/ 27.4 and DCR (%) 59.9/57.0 were for PemC vs PCB, respectively. Significantly more drug-related grade 3/4 anemia (18.7% vs 5.4%), and thrombocytopenia (24.0% vs 9.6%) were seen on PemC; significantly more grade 3/4 neutropenia (48.8% vs 24.6%) and grade 1/2 alopecia (28.3 % vs 8.2%) were seen on PCB. Conclusions: PemC was not superior to PCB in G4PFS; no difference in PFS or OS was observed for the two- vs three-drug regimens. There were no unexpected toxicities; the toxicity profiles demonstrated distinctions by arm, and both regimens demonstrated tolerability. Clinical trial information: NCT00948675.

18-month efficacy and safety update from JAVELIN Merkel 200 part A: A phase II study of avelumab in metastatic Merkel cell carcinoma progressed on chemotherapy.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 192-192 ◽  
Author(s):  
Sandra P. D'Angelo ◽  
Jeffery Scott Russell ◽  
Shailender Bhatia ◽  
Omid Hamid ◽  
Janice M. Mehnert ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Objective Response ◽  
Safety Data ◽  
Progression Free Survival ◽  
Merkel Cell ◽  
Efficacy And Safety ◽  
Duration Of Response ◽  
Grade 3

192 Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer. Avelumab, a human anti–PD-L1 monoclonal antibody, is FDA and EMA approved for the treatment of metastatic MCC (mMCC). Here, we report efficacy and safety data for avelumab in patients (pts) with mMCC at ≥18-mo of follow-up. Methods: Pts with mMCC and progression on prior chemotherapy received avelumab 10 mg/kg IV Q2W. Objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) were evaluated by independent review committee (RECIST v1.1) with tumor assessment every 6 wks; overall survival (OS) and adverse events (AEs; NCI CTCAE v4.0) were also evaluated. Results: As of Mar 24, 2017, 88 pts were treated and followed for a median of 23.0 mo (range 18.7–32.0). Median treatment duration was 17 wks (range 2–132; mean 35 wks ±37). Treatment was ongoing in 15 pts (17%); 7 pts (8%) voluntarily discontinued with continuing responses (5 complete responses [CR] and 2 partial responses). Other reasons for discontinuation were disease progression (n = 42; 48%), death (n = 10; 11%), AE (n = 8; 9%), or consent withdrawal/other (n = 6; 7%). Confirmed ORR of 33% (95% CI 23.3–43.8; CR in 11.4%) remained unchanged from previous analysis and median DOR has not been reached (range 2.8–24.9 mo; 95% CI 18.0–not estimable). Responses were ongoing in 20/29 pts (69%), including 5 pts with > 2 y of follow-up. PFS curve showed a plateau with identical 12- and 18-mo rates of 29% (95% CI 19–39). Median OS was 12.6 mo (95% CI 7.5-19.0) and the 12- and 18-mo OS rates were 51% (95% CI 40–61) and 40% (95% CI 29–50), respectively. 66 pts (75%) had a treatment-related (TR)AE, most commonly ( > 10%) fatigue (25%), infusion-related reaction (15%; all grade 1/2), nausea (11%), and diarrhea (11%); 8 (9%) had a grade ≥3 TRAE. 17 pts (19%) had an immune-related AE, which was grade ≥3 in 4 pts (4.5%). No treatment-related deaths occurred. Conclusions: Updated results demonstrate continued durable antitumor activity of avelumab in pts with mMCC, beyond that expected with cytotoxic chemotherapy. The median OS exceeding 1 y and manageable safety profile of avelumab signify a clinically meaningful benefit in pts with mMCC. Clinical trial information: NCT02155647.

First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9000-9000
Author(s):  
Martin Reck ◽  
Tudor-Eliade Ciuleanu ◽  
Manuel Cobo ◽  
Michael Schenker ◽  
Bogdan Zurawski ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Performance Status ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Expression Level ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]

Association of statins and nivolumab activity in patients with metastatic renal cell carcinoma (mRCC): Results from the phase II nivoren—GETUG AFU 26 trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 359-359
Author(s):  
Emeline Colomba ◽  
Ronan Flippot ◽  
Cécile Dalban ◽  
Sylvie Negrier ◽  
Christine Chevreau ◽  
...  
Keyword(s):  
Phase Ii ◽  
Immune Modulation ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Population Based ◽  
Metabolic Reprogramming ◽  
Oncogenic Signaling ◽  
Grade 3 ◽  
The Impact

359 Background: Statins are HMG-CoA inhibitors that regulate several mechanisms involved in tumor growth, including mitochondrial metabolism, activation of oncogenic signaling pathways, and immune modulation. Population-based studies showed that statin intake may be negatively associated with RCC onset. The impact of statins on response to immunotherapy in mRCC is unknown. Herein we study the association between statin administration and outcomes in patients with mRCC treated with nivolumab in the NIVOREN-GETUG AFU 26 phase II trial (NCT03013335). Methods: Patients with mRCC who failed previous VEGFR inhibitors were included. We assessed nivolumab activity, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) according to statin intake at baseline. Toxicity was assessed using CTCAE v4.0. Results: Overall,133 patients were treated with statins at baseline among 702 evaluable for concomitant therapies (19%). Among them, median age was 68 (49-90), 84% were male, 85% had a performance status ≥ 80%, 42% were overweight and 20% obese. Patients treated with statins had mostly good (23%) or intermediate (58%) IMDC risk, 64% had grade 3 or 4 tumors, and nivolumab was given in a third line setting or more in 55%. Median follow-up was 23.9 months (95%CI 23.0-24.5) in the overall cohort. The ORR was 26% in patients treated with statins, PFS 5.0 months (CI95% 3.0 – 5.5), OS 27.9 months (CI95% 19.4-30.3). Outcomes of patients with or without statins did not differ significantly. Similar rates of grade 3-5 TRAE were reported in patients with (20%) or without (18%) statin intake. Conclusions: This is the first study to evaluate statin intake and outcomes with nivolumab in patients with mRCC. Despite numerically higher ORR, statins were not significantly associated with improved outcomes. These data require other analyzes considering other factors such as BMI and other comorbidities. Further studies may help better understand the interplay between immunity and metabolic reprogramming in RCC.

scholarly journals 413 Toripalimab in combination with concurrent chemoradiation in patients with advanced/metastatic esophageal carcinoma: protocol for a single-arm, prospective, open-label, phase II clinical trial

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A444-A444
Author(s):  
Lei Wu ◽  
Yi Wang ◽  
Gang Wan ◽  
Jiahua Lv ◽  
Qifeng Wang ◽  
...  
Keyword(s):  
Esophageal Carcinoma ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Stage Iv ◽  
Predictive Biomarkers ◽  
Primary Objective ◽  
High Morbidity ◽  
Efficacy And Safety ◽  
Open Label ◽  
Carboplatin Auc

BackgroundEsophageal carcinoma is a disease with high morbidity and mortality in China and, recently, Immune checkpoint inhibitors(ICIs) combined with chemotherapy have shown good efficacy and safety for treatment; however, some patients still suffer from tumor progression or metastasis after treatment. Clinical studies have confirmed that immunotherapy combined with chemoradiotherapy can significantly improve the prognosis of patients with advanced esophageal cancer, but the efficacy and safety of adding radiotherapy to immunotherapy and chemotherapy have been less reported.MethodsThis is an open-label, single-arm, and single-center phase ll trial.Patients with unresectable stage IV esophageal squamous cell carcinoma(ESCC) who had not received prior systemic therapy were enrolled. The patients were treated with two cycles of toripalimab (240 mg d1, Q3W) combined with induction chemotherapy (paclitaxel 135–175 mg/m2, d1+carboplatin AUC=4–6, d1, Q3W), sequentially combined with concurrent chemoradiotherapy (30–50 Gy in 15–25 fractions, paclitaxel 135–175 mg/m2, d1+carboplatin AUC=4–6 d1, Q3W), followed by maintenance treatment with toripalimab (240 mg d1, Q3W) for 1 year. The primary objective of this trial is to evaluate the progression-free survival (PFS) of this combination therapy;and the secondary objective is related to the assessment of objective response rate (ORR), the disease control rate (DCR), the duration of remission (DOR), the 1- and 2-year overall survival(OS) rates, the safety and tolerability of patients to treatment, and the identification of the changes in the health-related quality of life (HRQoL) of patients. Furthermore, we aimed to identify predictive biomarkers (such as the expression of PD-L1 ctDNA and cytokines) and to explore the relationship between these biomarkers and tumor response to the study treatment.AcknowledgementsWe thank all the participants and their advisors involving in this study. We owe thanks to the patients in our study and their family members.Trial RegistrationChiCTR(ChiCTR2100046715). Registered on the 27th of May 2021.Ethics ApprovalThe study protocol is approved by Ethics Committee of Sichuan Cancer Hospital (SCCHEC-02-2021-021).Changes to the protocol will be communicated via protocol amendment by the study principal investigators. Written informed consent will be obtained from all participants.

Efficacy and safety of PD-1/PD-L1 and CTLA-4 immune checkpoint inhibitors in colorectal cancer: a meta-analysis

2022 ◽  
Author(s):  
Chunhui Jin ◽  
Xiaodan Zhu ◽  
Xiaona Huang ◽  
Tingjie Gong ◽  
Zhipeng Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Rate ◽  
Mismatch Repair ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Adverse Event Rate ◽  
Efficacy And Safety ◽  
Deficient Mismatch Repair

Aims: To evaluate the efficacy and safety of PD-1/PD-L1 and/or CTLA-4 inhibitors in the treatment of colorectal cancer (CRC) by meta-analysis. Methods: Electronic databases were searched. Eligible studies included investigations of efficacy and safety of anti-PD-1/PD-L1 or anti-CTLA-4 agents in patients with CRC. Corresponding indicators were calculated. Results: A total of 15 articles were included. The pooled objective response rate, overall survival rate, progression-free survival rate and adverse event rate were 33, 56, 46 and 59%, respectively. The objective response rates for CRC with deficient mismatch repair and CRC with proficient mismatch repair were 43 and 3%, respectively, in patients treated with PD-1 inhibitors. Conclusion: The authors' study indicates that PD-1/PD-L1 inhibitors manifest promising clinical responses in the treatment of CRC with deficient mismatch repair with acceptable treatment-related adverse events.

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