Phase III study of tislelizumab plus chemotherapy vs chemotherapy alone as first-line (1L) treatment for advanced squamous non-small cell lung cancer (sq NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9554-9554
Author(s):  
Jie Wang ◽  
Xinmin Yu ◽  
Shun Lu ◽  
Yanping Hu ◽  
Yuping Sun ◽  
...  
Keyword(s):  
Tumor Stage ◽  
Median Number ◽  
Phase Iii ◽  
Tolerability Profile ◽  
Open Label ◽  
Open Label Phase ◽  
Independent Review ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Number Of Treatment

9554 Background: Tislelizumab is an anti-PD-1 antibody engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis. Tislelizumab in combination with chemotherapy has demonstrated a manageable tolerability profile and preliminary efficacy as 1L treatment for NSCLC. Methods: In this open-label phase 3 study (NCT03594747), Chinese pts with histologically confirmed stage IIIB or IV sq NSCLC were randomized (1:1:1) to receive IV Q3W: tislelizumab (200 mg, D1) + paclitaxel (P; 175 mg/m2, D1) and carboplatin (carb; AUC 5, D1) ( Arm A); tislelizumab + nab-P (100 mg/m2; D1, 8, and 15) and carb (AUC 5, D1) ( Arm B); or P (175 mg/m2, D1) and carb (AUC 5, D1) ( Arm C). Chemotherapy was administered for 4-6 cycles followed by tislelizumab. Patients were stratified by tumor stage and PD-L1 expression. The primary endpoint, PFS per RECIST v1.1, was assessed by Independent Review Committee; key secondary endpoints included OS, ORR, DoR, and safety/tolerability. Results: Across 360 pts, median PFS was significantly improved with tislelizumab plus chemotherapy ( Arms A and B) compared with chemotherapy alone ( Arm C) (Table). As of 6 Dec 2019, ORRs were higher and median DoRs were longer in Arms A and B vs Arm C. Across all arms, median OS was not reached and median number of treatment cycles were comparable. Adverse events (AEs) leading to discontinuation of any treatment were reported in 12.5%, 29.7%, and 15.4% of pts in Arms A, B, and C, respectively. The most commonly reported grade ≥3 AEs were hematologic in nature (eg, neutropenia) and consistent with known chemotherapy AEs. Serious treatment-related AEs (TRAEs) were reported in 72 pts (37.5% [ A]; 38.9% [ B]; 23.6% [ C]); TRAEs leading to death were reported in 6 pts (n=1 [ A]; n=2 [ B]; n=3 [ C]), none of which were solely attributed to tislelizumab. Conclusions: As 1L treatment for advanced sq NSCLC, addition of tislelizumab to P/carb or nab-P/carb chemotherapy significantly improved PFS and showed higher ORR and longer DoR than chemotherapy alone. The safety profile is in line with the known profiles of tislelizumab, chemotherapy, and underlying NSCLC; no new safety signals were identified with addition of tislelizumab to chemotherapy. Clinical trial information: NCT03594747 . [Table: see text]

Exploratory analyses of efficacy and safety of pemetrexed (Pem) plus bevacizumab (Bev) and bev alone as maintenance therapy (MT) in patients (Pts) with stage IIIb or IV nonsquamous non-small cell lung cancer (NS-NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8012-8012
Author(s):  
Jyoti D. Patel ◽  
Edward B. Garon ◽  
Ramaswamy Govindan ◽  
Craig H. Reynolds ◽  
David R. Spigel ◽  
...  
Keyword(s):  
Survival Rates ◽  
Sensory Neuropathy ◽  
Median Number ◽  
Stage Iiib ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Open Label ◽  
Open Label Phase ◽  
The Difference ◽  
Grade 3

8012 Background: In a phase III superiority study, Pem+carboplatin (Cb)+Bev followed by Pem+Bev improved PFS compared with paclitaxel (Pac)+Cb+Bev followed by Bev in NS-NSCLC pts. Superior OS (primary endpoint) was not met. These analyses assessed the efficacy and safety in pts who received MT. Methods: Prespecified exploratory analyses were performed in the maintenance population (MP) and timed from the start of induction. Pts ≥18 years with stage IIIB/IV NS-NSCLC (ECOG status 0–1) from the multicenter, randomized, open-label, phase III superiority study were included in the MP if they received at least one dose of MT. For MT, pts received intravenous Pem 500 mg/m2+Bev 15 mg/kg (n=292) or Bev 15 mg/kg (n=298). OS, PFS, and safety were evaluated. Comparison is made to the intent-to-treat (ITT; Pem=472, Pac=467) or safety population (SP; Pem=442, Pac=443; received at least one dose of one drug). Results: Baseline pt and disease characteristics for the ITT and MP were similar between arms. In the ITT/MP population, the median number of cycles was 7/10 (range, 1-41/4–41) in the Pem arm and 6/9 (range, 1-39/5–39) in the Pac arm. In the ITT/MP, OS was 12.6/17.7 months (mos; Pem) and 13.4/15.7 mos (Pac). Survival rates (%) at 12 and 24 mos with Pem (ITT/MP) were 52.7/71.7 and 24.4/34.5; Pac, 54.1/66.5 and 21.2/26.5%. In pts not receiving MT, OS was 4.7 mos (Pem) and 6.1 mos (Pac). PFS (mos) in the ITT/MT was 6.0/8.6 (Pem) and 5.6/6.9 (Pac). In pts not receiving MT, PFS was 2.3 mos and 2.5 mos with Pem and Pac, respectively. From induction, both SP/MP had significantly more grade 3/4 thrombocytopenia, anemia, and fatigue with Pem and neutropenia and sensory neuropathy with Pac (p≤0.001). During MT only, the difference in grade 3/4 neutropenia rates between arms was no longer significant. Conclusions: Improved efficacy outcomes were consistent with previous Pem maintenance and Bev studies and no new toxicities were observed. Clinical trial information: NCT00762034.

SELECT: Randomized phase III study of docetaxel (D) or pemetrexed (P) with or without cetuximab (C) in recurrent or progressive non-small cell lung cancer (NSCLC) after platinum-based therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7502-7502 ◽  
Author(s):  
Edward S. Kim ◽  
Marcus A. Neubauer ◽  
Allen Lee Cohn ◽  
Lee Steven Schwartzberg ◽  
Lawrence E. Garbo ◽  
...  
Keyword(s):  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Staining Intensity ◽  
Primary Objective ◽  
Phase Iii ◽  
Open Label ◽  
Duration Of Response ◽  
Independent Review ◽  
Secondary Endpoints

7502 Background: SELECT investigated whether the addition of C to standard chemotherapy improved progression-free survival (PFS) in patients (pts) with recurrent or progressive NSCLC after failure of platinum-based therapy. Methods: SELECT was a multicenter, open label, randomized phase III trial. Per investigator choice, pts received either P (500 mg/m2) or D (75 mg/m2) on day 1 and then were randomized within each group to chemotherapy plus C (400/250 mg/m2) (initial/weekly) or chemotherapy alone. Therapy was given for up to six 3-week cycles; pts randomized to C continued weekly monotherapy until disease progression or unacceptable toxicity. The primary objective was PFS for PC vs. P as determined by an Independent Review Committee (IRC). Secondary endpoints included overall survival (OS), objective response rate (ORR) and duration of response (DOR) by IRC, and safety. Preplanned subgroup analyses for epidermal growth factor receptor (EGFR) staining intensity by immunohistochemistry and histology were performed. Results for PC vs. P only are presented. Results: Between Jan 2005 and Feb 2010, 938 total pts were randomized. Baseline demographics were comparable between PC (n=301) and P (n=304): median age 64 years; male 60%; Caucasian 88%; KPS 80-100/60-70 84%/16%; squamous/non-squamous 24%/76%. Median PFS (months) PC: 2.89 and P: 2.76 (hazard ratio [HR] =1.03 [95% confidence interval (CI)=0.87-1.21]; p=0.76). Median OS (months) PC: 6.93 and P: 7.79 (HR=1.01 [95% CI=0.86-1.20]; p=0.86). ORR PC: 6.6% and P: 4.3% (odds ratio =1.59 [95% CI=0.78-3.26]; p=0.20). Median DOR (months) PC: 4.17 and P: 6.93 (HR=1.58 [95% CI=0.74-3.36]; p=0.24). There were no statistical differences in efficacy based on histology or EGFR staining intensity. More drug-related AEs/SAEs were observed in the PC arm, with differences mainly attributable to skin toxicities, GI (diarrhea/stomatitis), and hypomagnesemia. Conclusions: The addition of C to P did not improve efficacy in this pt population. Further biomarker analyses are planned. The safety profiles for C and P were consistent with existing data and no new safety signals were observed.

Randomized, open-label, phase II study comparing five-weekly S-1 plus cisplatin (SP) with tri-weekly capecitabine plus cisplatin (XP) in chemotherapy-naïve patients with HER2 negative advanced gastric cancer (AGC): OGSG 1105 HERBIS-4A trial.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 102-102
Author(s):  
Atsushi Takeno ◽  
Youichi Makari ◽  
Shunji Endo ◽  
Jin Matsuyama ◽  
Ryohei Kawabata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Open Label ◽  
Group 13 ◽  
Common Grade ◽  
Open Label Phase ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
To Receive

102 Background: This phase II study aimed to investigate the safety and efficacy of XP compared to SP in the first-line treatment of HER2 negative AGC. Methods: Patients were randomly assigned to receive either SP (S-1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/ m2 on day 8, every 5 weeks) or XP (capecitabine 1,000 mg/m2 twice daily for 14 days plus cisplatin 80 mg/m2 on day 1, every 3 weeks). Primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), and adverse events. Results: 84 eligible patients were randomly assigned to receive SP ( N = 41) or XP ( N = 43). No statistical difference was observed in overall RR between the SP and XP groups [51.2% (95% CI, 35.1% to 67.1%) vs. 53.5% (95% CI, 37.7% to 68.8%), P = 1.000]. Despite not significant, however, SP vs. XP showed a trend toward better PFS [median, 5.9 months vs. 4.1 months; hazard ratio (HR), 0.763; 95% CI, 0.462 to 1.259; P = .284] and OS (median, 13.5 months vs. 10.0 months; HR, 0.776; 95% CI, 0.485 to 1.244; P = .290). This trend in the SP vs. XP comparison was more pronounced in TTF (median, 4.5 months vs. 3.1 months; HR, 0.651; 95% CI, 0.421 to 1.006; P = .052). Common grade 3 to 4 hematological toxicities were neutropenia and anemia (SP group, 23% and 23%; XP group, 35% and 28%). Grade 3-4 anorexia and hyponatremia were more frequently seen in the XP group (31% and 16%) compared to the SP group (13% and 5%). Treatment-related deaths occurred in one patient (2.3%) in the XP group. Conclusions: XP failed to demonstrate the superior efficacy over SP. Higher incidence of severe toxicities by XP suggests SP as the standard 1st line chemotherapy for HER2 negative AGC in Japan. Clinical trial information: UMIN000006755.

Randomized phase III trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as perioperative chemotherapy for muscle invasive urothelial bladder cancer (MIUBC): Preliminary results of the GETUG/AFU V05 VESPER trial on toxicity and pathological responses.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 437-437 ◽  
Author(s):  
Stephane Culine ◽  
Gwenaelle Gravis ◽  
Aude Flechon ◽  
Michel Soulie ◽  
Laurent Guy ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Perioperative Chemotherapy ◽  
Urothelial Bladder ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Muscle Invasive ◽  
Dose Dense ◽  
Number Of Cycles

437 Background: The optimal perioperative chemotherapy regimen for patients (pts) with MIUBC is not defined. Methods: Between February 2013 and February 2018, 494 pts were randomized in 28 French centres and received either 4 cycles of GC every 3 weeks or 6 cycles of dd-MVAC every 2 weeks before surgery (neoadjuvant group) or after surgery (adjuvant group). The primary endpoint was the progression-free survival at 3 years. Secondary endpoints included toxicity, pathological responses and overall survival. Results: In the neoadjuvant group, 218 pts received dd-MVAC and 219 pts GC. The median number of cycles was 6 (0-6) and 4 (1-4), respectively. 60% of pts received 6 cycles in the dd-MVAC arm, 84% received 4 cycles in the GC arm. 199 pts (91%) and 198 (90%) pts underwent surgery, respectively. Complete pathologic responses (ypT0pN0) were observed in 84 (42%) and 71 (36%) pts, respectively (p=0.02). An organ-confined status (<ypT3pN0) was obtained in 154 (77%) and 124 (63%) pts, respectively (p=0.002). In the adjuvant group (57 pts), the median number of cycles was 5 (1-6) and 4 (1-4), respectively. 40% of pts received 6 cycles in the dd-MVAC arm, 60% received 4 cycles in the GC arm. Most of CTCAE grade ≥ 3 toxicities concerned hematological toxicities. At least one of these where reported for 125 (50%) pts in the dd-MVAC group and 134 (54%) pts in the GC group (p=NS). Gastrointestinal (GI) grade ≥ 3 disorders were more frequently observed in the dd-MVAC arm (p<0.0001) as well as grade ≥ 3 asthenia (p<0.00001). Four deaths (3 in the dd-MVAC) occurred during chemotherapy. Conclusions: Complete pathological responses and organ-confined status were more frequently observed in the dd-MVAC arm. Toxicity was manageable with more severe asthenia and GI side effects in the dd-MVAC arm. Clinical trial information: 2012-000563-25.

Olaparib plus paclitaxel plus carboplatin (P/C) followed by olaparib maintenance treatment in patients (pts) with platinum-sensitive recurrent serous ovarian cancer (PSR SOC): A randomized, open-label phase II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5001-5001 ◽  
Author(s):  
Amit M. Oza ◽  
David Cibula ◽  
Ana Oaknin ◽  
Christopher John Poole ◽  
Ron H.J. Mathijssen ◽  
...  
Keyword(s):  
Maintenance Treatment ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Open Label Phase ◽  
Secondary Endpoints ◽  
Grade 3

5001 Background: The oral PARP inhibitor olaparib has shown antitumor activity in pts with SOC. Our multicenter study compared the efficacy of (Arm A) olaparib capsules plus P/C for 6 cycles then maintenance olaparib monotherapy vs (Arm B) P/C alone for 6 cycles and no further therapy in pts with PSR SOC (NCT01081951). Methods: Pts received 6 x 21-day(d) cycles of olaparib (200 mg bid, d1–10/21) + P (175 mg/m2 iv, d1) + C (AUC4 iv, d1), then olaparib monotherapy as maintenance (400 mg bid, continuous) (Arm A), or 6 x 21d cycles of P (175 mg/m2 iv, d1) + C (AUC6 iv, d1) then no further therapy (Arm B), until progression. Randomization (1:1) was stratified by number of platinum treatments and platinum-free interval. Primary endpoint: progression-free survival (PFS) by central review (RECIST 1.1). Secondary endpoints: overall survival (OS), objective response rate (ORR), safety. Archival tissue was collected where available for analysis of biomarker correlation. Results: Of 162 pts randomized (n=81 per arm), 156 received treatment (Arm A, n=81; Arm B, n=75) and 121 began the maintenance/no further therapy phase (Arm A, n=66; Arm B, n=55). Olaparib + P/C (AUC4) followed by maintenance olaparib showed a significant improvement in PFS vs P/C (AUC6) alone (HR = 0.51, 95% CI 0.34, 0.77; P=0.0012; median = 12.2 vs 9.6 months). OS data are immature (total events: 14%). ORR was similar for Arm A and Arm B (64 vs 58%). Most common AEs during the combination phase were alopecia (74 vs 59%), nausea (69 vs 57%) and fatigue (64 vs 57%) for Arm A vs Arm B, respectively. Pts with grade ≥3 AEs (65 vs 57%), serious AEs (SAEs: 15 vs 21%) and AEs leading to treatment discontinuation (19 vs 16%) were similar for Arm A vs Arm B. Most common AEs during maintenance/no further therapy were nausea (50 vs 6%) and vomiting (29 vs 7%). 29 vs 16% of pts had grade ≥3 AEs, 9 vs 7% had SAEs and 8% vs N/A discontinued due to AEs in the olaparib vs no treatment arms, respectively. There were no fatal AEs. Conclusions: In pts with PSR SOC, olaparib plus P/C (AUC4) followed by olaparib 400 mg bid monotherapy maintenance treatment resulted in a significant improvement in PFS vs P/C (AUC6) alone.

Phase II trial of panobinostat (LBH589) in patients (pts) with refractory metastatic colorectal cancer (MCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 582-582 ◽  
Author(s):  
Philip Jordan Gold ◽  
David A. Smith ◽  
Desiree Iriarte ◽  
Barry Boatman ◽  
Henry G. Kaplan
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Median Number ◽  
Open Label ◽  
Ecog Performance Status ◽  
Treatment Regimes ◽  
Open Label Phase ◽  
Secondary Endpoints

582 Background: LBH589 is a novel histone deacetylase inhibitor (HDACi) which induces apoptosis of tumor cells. LBH589 has been shown to cause regression of colon cancer in animal models and phase I trials have shown the agent to be well tolerated, providing rationale for studying this agent in pts with MCRC. Methods: This was a multicenter, open-label phase II study of single agent LBH589 in patients with MCRC who failed at least 2 prior regimens for metastatic disease. Measurable disease, adequate organ function and ECOG performance status of 0-2 were required. Pts received LBH589 30mg po on M/W/F until disease progression. Pts were evaluated for toxicity every 2 weeks and for response every 8 weeks. The primary endpoint was overall survival. Secondary endpoints included response rate, time to progression (TTP), and toxicity. Results: 29 pts were enrolled (16 male, 13 female). The median age was 59 (range 41-76). The median number of prior treatment regimes was 3 (2-11). The median survival was 5.1 months (range 1-24+). There were no objective responses. 3 pts had SD at 8 weeks. The median TTP was 7.7 weeks (range 1-38.). Six pts had grade 4 thrombocytopenia requiring platelet transfusion. Nine pts required dose reductions for toxicity. Conclusions: Single-agent LBH589 was not associated with objective tumor responses in this heavily pre-treated pt population. However, the median survival was comparable to that seen in other trials of single agent targeted therapy in the treatment of refractory MCRC. Thrombocytopenia was significant, and may complicate potential trials of combination therapy.

A randomized phase III trial of S-1/oxaliplatin (SOX) plus bevacizumab versus 5-FU/l-LV/oxaliplatin (mFOLFOX6) plus bevacizmab in patients with metastatic colorectal cancer: The SOFT study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3519-3519 ◽  
Author(s):  
Daisuke Takahari ◽  
Yasuhide Yamada ◽  
Hiroshi Matsumoto ◽  
Hideo Baba ◽  
Kazuhiro Yoshida ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
P Value ◽  
Open Label ◽  
Phase Iii Trial ◽  
Open Label Phase ◽  
Grade 3 ◽  
Ecog Ps

3519 Background: Several studies of oxaliplatin plus S-1 combination therapy (SOX) conducted in Asia have shown promising efficacy and safety for metastatic colorectal cancer (mCRC), suggesting the potential to replace mFOLFOX6. We performed a randomized phase III trial to determine whether SOX plus bevacizmab (SOX+Bev) is non-inferior to mFOLFOX6 plus bevacizmab (mFOLFOX6+Bev) in terms of progression-free survival (PFS). Methods: The SOFT study was a randomized, open-label, phase III trial. Chemotherapy-naïve patients (pts) with mCRC, an ECOG PS of 0-1, and adequate organ functions were randomized to receive either mFOLFOX6+Bev (5 mg/kg of bevacizumab, followed by 200 mg/m2 of l-leucovorin given simultaneously with 85 mg/m2 of oxaliplatin, followed by a 400 mg/m2 bolus of 5-FU on day 1 and then 2,400 mg/m2 of 5-FU over 46 h, every 2 weeks) or SOX+Bev (7.5 mg/kg of bevacizumab, 130 mg/m2 of oxaliplatin on day 1, and 40−60 mg of S-1 twice daily for 2 weeks, followed by a 1-week rest). The primary endpoint was PFS. A sample size of 225 pts per group was estimated to be necessary based on a median PFS of 10.0 months in each group and an 80% power to demonstrate non-inferiority of SOX+Bev with a 2.5-month margin (hazard ratio, HR = 1.33) and a 2-sided alpha of 0.05. Results: A total of 512 pts were enrolled from February 2009 to March 2011. Data were analyzed after confirming >388 events as planned. Demographic factors were well balanced. Pts received a median of 12 cycles (1 cycle = 2 weeks) of mFOLFOX6+Bev and 8 cycles (1 cycle = 3 weeks) of SOX+Bev (range: 1−16). Median PFS was 11.5 months (95% CI: 10.7−13.2) with mFOLFOX6+Bev and 11.7 months (95% CI: 10.7−12.9) with SOX+Bev. The adjusted HR for PFS was 1.043 (95% CI: 0.860−1.266), and the p value for non-inferiority was 0.0139. Response rate was 62.7% with mFOLFOX6+Bev and 61.5% with SOX+Bev. Grade 3/4 toxicities (%) with mFOLFOX6+Bev/SOX+Bev were leukopenia 8.4/2.4, neutropenia 33.7/8.8, anorexia 1.2/5.2, and diarrhea 2.8/9.2. Conclusions: SOX+Bev is non-inferior to mFOLFOX6+Bev with respect to PFS as 1st-line treatment for mCRC and thus can replace mFOLFOX6+Bev. Clinical trial information: JapicCTI-090699.

Pomalidomide plus low-dose dexamethasone (POM + LoDEX) versus high-dose dexamethasone (HiDEX) in relapsed/refractory multiple myeloma (RRMM): Impact of cytogenetics in MM-003.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8528-8528
Author(s):  
Hartmut Goldschmidt ◽  
Meletios A. Dimopoulos ◽  
Katja C. Weisel ◽  
Philippe Moreau ◽  
Martha Lacy ◽  
...  
Keyword(s):  
High Risk ◽  
Progression Free Survival ◽  
Phase Iii ◽  
High Dose ◽  
Open Label ◽  
High Dose Dexamethasone ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Intent To Treat

8528 Background: RRMM patients (pts) who fail lenalidomide (LEN) and bortezomib (BORT) have poor prognosis. High-risk cytogenetics predict shorter survival. POM + LoDEX has demonstrated efficacy in pts with prior LEN and BORT and high-risk cytogenetics. MM-003 is an open-label, multicenter, phase III trial comparing POM + LoDEX vs. HiDEX in RRMM pts who failed LEN and BORT treatment (Tx) and have progressed on their last therapy. Methods: Pts must have been refractory to the last prior Tx (progressive disease [PD] during or within 60 days) and failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination). Randomization was 2:1 to POM 4 mg D1–21 + DEX 40 mg (20 mg for pts aged > 75 y) weekly; or DEX 40 mg (20 mg for pts aged > 75 y) D1–4, 9–12, and 17–20 (28-day cycles). Tx continued until PD or unacceptable adverse events (AEs). The primary endpoint was progression-free survival (PFS). Secondary endpoints included OS and AEs. This analysis examined pts meeting modified high-risk cytogenetic criteria—del(17p13) and/or t(4p16/14q32). Results: 302 pts received POM + LoDEX, and 153 pts received HiDEX. 225 and 107 pts, respectively, were evaluable for cytogenetics. Baseline characteristics were similar. Median PFS and OS were significantly longer with POM + LoDEX vs. HiDEX, regardless of cytogenetic risk (Table). The most common grade 3/4 AEs were neutropenia, anemia, and infection (Table). Discontinuation due to AE was low: 4% vs. 6% (high risk) and 10% vs. 4% (standard risk). Conclusions: Median PFS and OS were significantly longer with POM + LoDEX vs. HiDEX in pts with cytogenetically-defined high-risk disease, consistent with results from the intent-to-treat population. Tolerability was acceptable. POM + LoDEX should be considered a new Tx option in pts failing LEN and BORT. Clinical trial information: NCT01311687. [Table: see text]

Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): Updated results from the phase III CASPIAN study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9002-9002 ◽  
Author(s):  
Luis G. Paz-Ares ◽  
Mikhail Dvorkin ◽  
Yuanbin Chen ◽  
Niels Reinmuth ◽  
Katsuyuki Hotta ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Standard Of Care ◽  
Analysis Data ◽  
Phase Iii ◽  
Open Label ◽  
Primary Endpoints ◽  
Open Label Phase ◽  
First Results ◽  
Treatment Naïve ◽  
Grade 3

9002 Background: CASPIAN is an open-label, Phase 3 study of durvalumab (D) ± tremelimumab (T) + etoposide and either cisplatin or carboplatin (EP) for pts with 1L ES-SCLC. At the planned interim analysis (data cutoff Mar 11, 2019; 63% maturity), D + EP demonstrated a statistically significant improvement in OS compared with EP alone (HR 0.73 [95% CI 0.59–0.91]; p=0.0047). Here we present a planned updated analysis of OS for D + EP vs EP and the first results for D + T + EP vs EP. Methods: Treatment-naïve pts with ES-SCLC (WHO PS 0/1) were randomized 1:1:1 to D 1500 mg + EP q3w, D 1500 mg + T 75 mg + EP q3w, or EP q3w. In the IO arms, pts received 4 cycles of EP + D ± T, followed by maintenance D 1500 mg q4w until disease progression. Pts received one additional dose of T 75 mg post EP in the D + T + EP arm. In the EP arm, pts received up to 6 cycles of EP and optional PCI (investigator’s discretion). The two primary endpoints were OS for D + EP vs EP and for D + T + EP vs EP. Results: 268, 268 and 269 pts were randomized to D + EP, D + T + EP and EP, respectively; baseline characteristics were generally well balanced across arms. As of Jan 27, 2020, the median follow-up was 25.1 mo, 82% maturity. D + EP continued to demonstrate improvement in OS vs EP, with a HR of 0.75 (95% CI 0.62–0.91; nominal p=0.0032); median OS 12.9 vs 10.5 mo, respectively. 22.2% of pts were alive at 2 y with D + EP vs 14.4% of pts with EP. D + T + EP numerically improved OS vs EP, however this did not reach statistical significance per the prespecified statistical plan: HR 0.82 (95% CI 0.68–1.00; p=0.0451 [p≤0.0418 required for stat sig]); the median OS was 10.4 mo and 23.4% of pts were alive at 2 y. Secondary endpoints of PFS and ORR remained improved with D + EP vs EP and will be presented. Confirmed investigator-assessed ORR was similar for D + T + EP vs EP (58.4% vs 58.0%). Median PFS was similar for D + T + EP vs EP (4.9 mo vs 5.4 mo), but the 12-mo PFS rate was numerically higher (16.9% vs 5.3%); PFS HR 0.84 (95% CI 0.70–1.01). In the D + EP, D + T + EP and EP arms, respectively, incidences of all-cause AEs of Grade 3/4 were 62.3%, 70.3% and 62.8%; AEs leading to discontinuation 10.2%, 21.4% and 9.4%; and AEs leading to death 4.9%, 10.2% and 5.6%. Conclusions: The addition of durvalumab to EP continued to demonstrate improvement in OS compared with a robust control arm, further supporting this regimen as a new standard of care for 1L ES-SCLC offering the flexibility of platinum choice. No additional benefit was observed when T was combined with D + EP in this pt population. Safety findings in all arms remained consistent with the known safety profiles of all agents. Clinical trial information: NCT03043872.

Safety of Treatment (Tx) with Pomalidomide (POM) and Low-Dose Dexamethasone (LoDEX) in Patients (Pts) with Relapsed or Refractory Multiple Myeloma (RRMM) and Renal Impairment (RI), Including Those on Dialysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 374-374 ◽  
Author(s):  
Karthik Ramasamy ◽  
Meletios A. Dimopoulos ◽  
Niels W.C.J. van de Donk ◽  
Barbara Gamberi ◽  
Frank Bridoux ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Median Number ◽  
Comparable Efficacy ◽  
Open Label ◽  
Advisory Committees ◽  
Open Label Phase ◽  
Grade 3 ◽  
Dose Modifications ◽  
Support Research

Abstract Background: RI occurs in ≈ 20%-30% of newly diagnosed MM pts and is associated with poor prognosis (Knudsen et al. Eur J Haematol. 2000; Kyle et al. Mayo Clin Proc. 2003). Data from 2 pivotal trials (MM-002, MM-003) suggested comparable efficacy and tolerability of POM + LoDEX in pts with or without moderate RI (Siegel ASH 2012; Weisel ASCO 2013). However, these trials excluded pts with severe RI. MM-013 (NCT02045017) is a European multicenter, open-label phase 2 study designed to assess the efficacy, safety, and pharmacokinetics of POM + LoDEX in RRMM pts with moderate or severe RI, including those on dialysis. Methods: The trial is enrolling RRMM pts (N = 80) across 3 cohorts: cohort A (moderate RI, estimated glomerular filtration rate [eGFR] ≥ 30 to < 45 mL/min/1.73 m2, n = 33), cohort B (severe RI without dialysis, eGFR < 30 mL/min/1.73 m2, n = 33), and cohort C (severe RI requiring dialysis, n = 14). Pts must have MM-related RI and have received ≥ 1 prior Tx (including lenalidomide). POM 4 mg is administered on days 1-21 of a 28-day cycle and LoDEX 40 mg/day (20 mg for pts aged > 75 yrs) on days 1, 8, 15, and 22 until progressive disease (PD) or unacceptable toxicity. At the time of submission of this abstract, 17 pts terminated Tx; this abstract focuses on tolerability in these pts. Results: This trial is still recruiting; at the time of data cutoff for this abstract, 39 pts were enrolled. Data are included for 17 pts who discontinued Tx. Of all 39 pts, 12 were assigned to cohort A, 18 to cohort B, and 9 to cohort C. The median age of the total population was 72 yrs (range, 52-86 yrs), with 67.7% being male. The median number of prior lines of therapy was 4.0 (3.5 in cohort A, 5.0 in cohort B, and 3.0 in cohort C). This distribution was similar in the 17 pts who discontinued Tx so far (4, 7, and 6 in cohorts A, B, and C, respectively), with a median age of 72 yrs and 58.8% being male. Reasons for discontinuation of Tx were PD (7 pts), adverse events (AEs; 3 pts), death (5 pts: 2 pts due to PD, 2 pts due to infections, 1 pt due to hyperkalemia), and other reasons (2 pts: 1 pt aged 86 yrs with general health problems, 1 pt with increasing RI). Median Tx duration in these pts was 6.9 weeks in cohort A, 12.6 weeks in cohort B, and 12.9 weeks in cohort C. The dosage of POM was reduced to 3 mg in 3 pts (1 patient in each cohort), in all cases due to an AE (thrombocytopenia in 2 pts, pneumonia in 1 pt). However, no further Tx reductions occurred. The most frequent toxicity of any grade in the pts who discontinued was hematologic (82.4% [14 pts]), notably neutropenia in 58.8% (50% in cohort A, 42.9% in cohort B, 83.3% in cohort C), anemia in 52.9% (50% in cohort A, 28.6% in cohort B, 83.3% in cohort C), and thrombocytopenia in 52.9% (75% in cohort A, 14.3% in cohort B, 83.3% in cohort C). Grade 3/4 neutropenia occurred in 47.1%; grade 3/4 thrombocytopenia occurred in 35.3%. Notably, febrile neutropenia was reported in only 1 pt in cohort A. Granulocyte colony-stimulating factor was used in 52.9% of pts. Non-hematologic AEs were less frequent. Infections occurred in 7 pts (41.2%), all of which were pulmonary infections, with the exception of 1 case of nasopharyngitis. Asthenia (23.5%) and fatigue (23.5%) occurred predominantly in cohort C. No thromboembolic events or secondary primary malignancies have been reported to date. Conclusions: These data suggest that the combination of POM and LoDEX can be safely administered in pts with RI. A starting dose of POM 4 mg can be used throughout all stages of RI, and the side effects seen in this population have been previously reported with POM use (ie, mainly hematologic events and infections). Rates of neutropenia and thrombocytopenia are similar to reports in a non-RI population. Dose modifications should be considered in pts who develop neutropenia and thrombocytopenia; in pts showing signs of infections, dose interruptions may be considered. Disclosures Off Label Use: Pomalidomide in MM patients with renal insufficiency.. Dimopoulos:Janssen: Honoraria; Celgene: Honoraria; Janssen-Cilag: Honoraria; Genesis: Honoraria; Onyx: Honoraria; Novartis: Honoraria; Amgen: Honoraria. van de Donk:Janssen Pharmaceuticals: Research Funding; Amgen: Research Funding; Celgene: Research Funding. Gamberi:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Kueenburg:Celgene Corporation: Consultancy, Honoraria. Rosettani:Celgene Corporation: Employment. Collins:Celgene Corporation: Employment. Lersch:Celgene Corporation: Employment. Bacon:Celgene Corporation: Employment, Equity Ownership. Weisel:Noxxon: Consultancy; Celgene: Consultancy, Honoraria, Other: Travel Support, Research Funding; BMS: Consultancy, Honoraria, Other: Travel Support; Novartis: Other: Travel Support; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Travel Support, Research Funding; Onyx: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel Support. Sonneveld:Amgen: Honoraria, Research Funding; Karyopharm: Research Funding; SkylineDx: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

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