Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1008-1008 ◽  
Author(s):  
Sylvia Adams ◽  
Peter Schmid ◽  
Hope S. Rugo ◽  
Eric P. Winer ◽  
Delphine Loirat ◽  
...  
Keyword(s):  
Primary Endpoints ◽  
Phase 2 Study ◽  
Heavily Pretreated ◽  
Secondary Endpoints ◽  
Positive Score ◽  
Previously Treated ◽  
Combined Positive Score ◽  
Grade 3 ◽  
Ecog Ps

1008 Background: In KEYNOTE-012, pembro showed durable activity and manageable safety in patients (pts) with PD-L1+ mTNBC. Cohort A of KEYNOTE-086 (NCT02447003) examined the efficacy/safety of pembro in previously treated mTNBC, regardless of PD-L1 expression. Methods: Pts with centrally confirmed mTNBC, ≥1 prior chemotherapy for metastatic disease, and ECOG PS 0-1 had pembro 200 mg Q3W for up to 24 mo; imaging q 9 wk for the first 12 mo, then q 12 wk. Clinically stable pts with PD could remain on pembro until PD confirmed on next assessment. Primary endpoints: ORR (RECIST v1.1, central review) in all pts and pts with PD-L1+ tumors, and safety. Secondary endpoints: DOR, disease control rate (DCR; CR + PR + SD ≥24 wk), PFS, and OS. Planned enrollment was 160 pts; analysis based on data as of Nov 10, 2016. Results: 60% of screened PD-L1-evaluable pts had PD-L1+ tumors (combined positive score ≥1%). Of 170 pts enrolled (100% women; median age 54 y), 44% had ≥3 prior lines of therapy, 51% had elevated LDH, 74% had visceral mets and 62% had PD-L1+ tumors. After a median follow-up of 10.9 mo, 9 (5%) pts remained on pembro. Treatment-related AEs (TRAEs) of any grade and grade 3-4 occurred in 60% and 12% of pts, respectively; 4% discontinued due to TRAEs. There were no deaths due to AE. Overall ORR was 5% regardless of PD-L1 expression (Table). Best overall response was 0.6% CR, 4% PR, 21% SD; not evaluable (3%). DCR was 8% (95% CI 4-13). Median DOR was 6.3 mo (range 1.2+ to 10.3+); 5 (63%) responders w/o PD at data cutoff. Median PFS and OS were 2.0 mo (95% CI 1.9-2.0) and 8.9 mo (95% CI 7.2-11.2), with 6-mo rates of 12% and 69%, respectively. ORR was numerically lower in pts with poor prognostic factors (e.g., high LDH, liver/visceral mets; Table). Conclusions: In KEYNOTE-086 Cohort A, pembro monotherapy showed manageable safety and durable responses in a subset of pts with heavily pretreated mTNBC. Randomized studies of monotherapy and combination therapy are ongoing. Clinical trial information: NCT02447003. [Table: see text]

KEYNOTE-365 cohort B: Pembrolizumab (pembro) plus docetaxel and prednisone in abiraterone (abi) or enzalutamide (enza)–pretreated patients with metastatic castration-resistant prostate cancer (mCRPC)—New data after an additional 1 year of follow-up.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 10-10
Author(s):  
Leonard Joseph Appleman ◽  
Michael Paul Kolinsky ◽  
William R. Berry ◽  
Margitta Retz ◽  
Loic Mourey ◽  
...  
Keyword(s):  
Oral Prednisone ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Psa Response ◽  
Positive Score ◽  
Previously Treated ◽  
Combined Positive Score ◽  
Grade 3

10 Background: For men with mCRPC, systemic therapies such as docetaxel and cabazitaxel improve survival, but more effective treatments are needed. KEYNOTE-365 (NCT02861573) is a phase 1b/2 study to examine the safety and efficacy of pembro in combination with 4 different study medications (cohorts A, B, C, D) in mCRPC. Previous data from cohort B with a median of 20 months of follow-up showed that pembro + docetaxel and prednisone was well tolerated and had antitumor activity in patients (pts) with mCRPC previously treated with abi or enza. New efficacy and safety data after an additional year of follow-up are presented. Methods: Cohort B enrolled pts who did not respond to or were intolerant to ≥4 weeks of abi or enza in the prechemotherapy mCRPC state and whose disease progressed within 6 months of screening (determined by PSA progression or radiologic bone/soft tissue progression). Pts received pembro 200 mg IV every 3 weeks (Q3W), docetaxel 75 mg/m2 IV Q3W, and oral prednisone 5 mg twice daily. Primary end points were safety, PSA response rate (PSA decrease >50% from baseline), and ORR per RECIST v1.1 by blinded independent central review. Efficacy and safety were assessed in all pts as treated. Results: Of the 104 treated pts, median age was 68.0 years (range, 50-86), 23.1% had PD-L1–positive tumors (combined positive score ≥1), 25.0% had visceral disease, and 50.0% had measurable disease. Median time from enrollment to data cutoff was 32.4 months (range 13.9-40.3); 101 pts discontinued, primarily because of disease progression (77.9%). Efficacy outcomes are reported in the table below. Treatment-related adverse events (TRAEs) occurred in 100 pts (96.2%); the most frequent (≥30%) were diarrhea (41.3%), fatigue (41.3%), and alopecia (40.4%). Grade 3-5 TRAEs occurred in 46 pts (44.2%). Five pts (4.8%) died of AEs; 2 were treatment-related pneumonitis. Conclusions: After another year of follow-up, pembro + docetaxel and prednisone showed improved ORR and PSA response rates compared to the prior dataset in pts with mCRPC previously treated with abi or enza. Safety was consistent with known profiles of each agent and will be further evaluated in a phase 3 study (KEYNOTE-921). Clinical trial information: NCT02861573. [Table: see text]

A phase 2 study of s-1 plus leucovorin in patients with untreated advanced cholangiocarcinoma (CCA).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 467-467
Author(s):  
Suebpong Tanasanvimon ◽  
Teerapat Ungtrakul ◽  
Nattaya Poovorawan ◽  
Napa Parinyanitikul ◽  
Chanida Vinayanuwattikun ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Primary Endpoints ◽  
Phase 2 Study ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Grade 3

467 Background: Patients with CCA usually present with advanced disease leading to the grave prognosis. Currently, cisplatin and gemcitabine is the standard treatment in advanced CCA. However, the CCA treatment outcomes are still poor and the options of treatment are quite limited. This study aimed to explore the efficacy and safety of S-1 plus leucovorin in patients with untreated advanced CCA. Methods: This single-arm two-center phase 2 study evaluated the efficacy and safety of S-1 40, 50 and 60 mg according to body surface area and leucovorin 15 mg , both given orally twice daily for one week, repeated every two weeks. Treatment was continued until complete 12 cycles, disease progression or unacceptable toxicity. The primary endpoints were overall response rate (ORR) and disease control rate (DCR) per RECIST version 1.1. The secondary endpoints were progression free survival (PFS), overall survival (OS) and toxicity. Results: Of total 32 patients and a median follow up time of 9.5 months, the ORR was 25% (95%CI 9.1-40.9) and the DCR was 62.5% (95% CI 44.8-80.2). In 25 response evaluable patients, the ORR was 32% (95% CI 12.4-51.7). The PFS was 8.0 (95%CI 5.59-10.4) months. The OS was 11.0 (95%CI 9.47-12.53). The most common grade 3 or 4 toxicities were anemia, mucositis and diarrhea. There was one patient discontinuing treatment due to treatment related toxicity. Conclusions: S-1 plus leucovorin was active and tolerable in patients with advanced CCA. Clinical trial information: TCTR20160313001.

KEYNOTE-059 cohort 1: Pembrolizumab (Pembro) monotherapy in previously treated advanced gastric or gastroesophageal junction (G/GEJ) cancer in patients (Pts) with PD-L1+ tumors—Asian subgroup analysis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 723-723
Author(s):  
Kei Muro ◽  
Charles S. Fuchs ◽  
Raymond Woo-Jun Jang ◽  
Taroh Satoh ◽  
Manuela Machado ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Prior Therapy ◽  
Phase 2 Study ◽  
The Us ◽  
Positive Score ◽  
Previously Treated ◽  
Combined Positive Score ◽  
Us Fda ◽  
Grade 3

723 Background: The US FDA approved pembro for treating pts with 1) recurrent locally advanced or metastatic G/GEJ adenocarcinoma, whose disease has progressed on or after ≥2 prior therapies and whose tumors express PD-L1 (combined positive score [CPS] ≥1), and 2) unresectable or metastatic, microsatellite instability-high (MSI-H) solid tumors that have progressed after prior therapy and who have no fitting options. We report Asian subgroup analyses from cohort 1 of KEYNOTE-059 (NCT02335411), a global, phase 2 study in advanced G/GEJ cancer. Methods: Eligible pts had measurable recurrent or metastatic G/GEJ adenocarcinoma whose disease has progressed on ≥2 prior chemotherapy regimens. Pts received pembro 200 mg Q3W up to 2 y. PD-L1+ tumors had a CPS ≥1. Primary end points were ORR (RECIST 1.1, by central review) and safety. Results: Cohort 1 enrolled 259 pts; 57% had PD-L1+ tumors. MSI status was evaluable in 174 tumor samples; of these, 7 were MSI-H. At data cutoff (4/21/2017), median (range) follow-up was 6 mo (1-25). Overall ORR was 12% (95% CI, 8-17) and median (range) DOR was 14 mo (2-19+). PFS6-mo rate was 15% and OS6-mo rate was 46%. In pts with PD-L1+ tumors, ORR was 16% (95% CI, 11-23) and median (range) DOR was 14 mo (3+-19+). In pts with PD-L1+ tumors, PFS6-mo rate was 20% and OS6-mo rate was 50%. In pts with MSI-H tumors, ORR was 57% (95% CI, 18-90) and median (range) DOR was not reached (5-14+ mo). In cohort 1, 41 pts were Asian and 218 pts were non-Asian. PD-L1+ tumors occurred in 42% of Asian pts and 60% of non-Asian pts. ORR was 12% (95% CI, 2-36) in Asian pts with PD-L1+ tumors and 17% (95% CI, 11-24) in non-Asian pts with PD-L1+ tumors. One of 7 pts with MSI-H tumors was Asian; this pt had CR. Grade 3-5 treatment-related AEs occurred in 17% and 18% of Asian and non-Asian pts, similar to the overall cohort. Conclusions: Pembro showed durable clinical benefit in previously treated pts with advanced G/GEJ cancer, especially those with PD-L1+ or MSI-H tumors. Safety and efficacy were similar in Asian and non-Asian pts. These findings highlight pembro as a standard treatment option in Asian and non-Asian pts with advanced G/GEJ cancer. Clinical trial information: NCT02335411.

Pembrolizumab in previously treated metastatic esophageal cancer: Longer term follow-up from the phase 2 KEYNOTE-180 Study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4032-4032 ◽  
Author(s):  
Ken Kato ◽  
Takashi Kojima ◽  
Daniel Hochhauser ◽  
Jaafar Bennouna ◽  
Antoine Hollebecque ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Phase 2 ◽  
Open Label ◽  
Heavily Pretreated ◽  
Positive Score ◽  
Previously Treated ◽  
Combined Positive Score

4032 Background: In the phase 2, open-label, KEYNOTE-180 (NCT02559687) study, after a median follow-up of 5.8 months, pembrolizumab (pembro) provided antitumor activity with durable responses in pts with previously treated, advanced/metastatic adenocarcinoma (EAC) including Siewert type 1 adenocarcinoma of the gastroesophageal junction or squamous cell carcinoma (ESCC) of the esophagus. Here we present results of an additional 10 months of follow-up. Methods: Eligible pts with metastatic esophageal cancer, ≥2 prior lines of therapy, and tumor samples evaluable for biomarker expression, received pembro 200 mg Q3W for up to 2 years, or until disease progression, unacceptable toxicity, or withdrawal. Tumor response was assessed Q9W (RECISTv1.1, central review). PD-L1+ pts had combined positive score ≥10 using IHC (22C3 antibody). Primary endpoint was objective response rate (ORR). Secondary endpoints included safety, DOR, PFS, and OS. Results: Of 121 pts enrolled, 63 (52%) had ESCC and 58 (48%) had PD-L1+ (combined positive score ≥10) tumors. As of July 30, 2018, median follow-up duration, from randomization to data cutoff, was 5.8 mo (range, 0.2 mo to 27.8+ mo). ORR (CR+PR) was 10% (95% CI, 5%-17%); 2 (2%) CR,10 (8%) PR, 25 (21%) SD. Median DOR was not reached ([NR] range, 2.1 mo to 25.1+ mo). Median PFS was 2 mo (95% CI, 1.9%-2.1%) with 9-mo PFS rate of 9%. Median OS was 5.8 mo (4.5-7.2) with 12 mo OS rate of 27%. In ESCC, ORR was 14% (95% CI, 7%-25%); 2 (3%) CR, 7 (11%) PR, with median DOR NR (range, 4.2 mo to 25.1+ mo). In EAC, ORR was 5% (95% CI, 1-14); 3 PR, with median DOR NR (range, 2.1 mo to 15.6+ mo). In PD-L1+ pts, ORR was 14% (95% CI, 6%-25%); 1 (2%) CR, 7 (12%) PR with median DOR NR (range, 4.2 mo to 25.1+ mo). In PD-L1- pts ORR was 6% (95% CI, 2%-16%); 1 (2%) CR, 3 (5%) PR; median DOR NR (range, 2.1 mo to 17.3+ mo). Overall, 19 (16%) pts had treatment-related grade 3-5 AEs. Seven (6%) pts discontinued due to a treatment-related AE. There was one treatment-related death from pneumonitis. Conclusions: Pembro continued to provide durable clinical benefit with a manageable safety profile for pts with heavily pretreated esophageal cancer, with conversions of PR to CR observed. Clinical trial information: NCT02559687.

Phase II study of the FGFR inhibitor AZD4547 in previously treated patients with FGF pathway-activated stage IV squamous cell lung cancer (SqNSCLC): LUNG-MAP sub-study SWOG S1400D.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9055-9055 ◽  
Author(s):  
Charu Aggarwal ◽  
Mary Weber Redman ◽  
Primo Lara ◽  
Hossein Borghaei ◽  
Philip C. Hoffman ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Grade 5 ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3

9055 Background: LungMAP is a National Clinical Trials Network umbrella trial for previously-treated SqNSCLC. S1400D is a phase II biomarker-driven therapeutic sub-study evaluating the FGFR inhibitor AZD4547 in patients (pts) with FGFR positive chemo-refractory SqNSCLC. Methods: Eligible pts had tumor FGFR alteration and/or mutation by next generation sequencing (Foundation Medicine), measurable disease, Zubrod PS 0-2, progression after 1 line of systemic therapy, and adequate end organ function. Receipt of prior immunotherapy was allowed. Eligible pts received AZD4547 80 mg bid orally. Primary endpoint was overall response rate (ORR) by RECIST; secondary endpoints included progression-free survival (PFS) and duration of response (DoR). Originally designed as a randomized trial of AZD4547 versus docetaxel, it was redesigned to be a single arm AZD4547 trial with the emergence of immunotherapy as standard 2ndline therapy. Forty pts were required to rule out an ORR of < = 15% if the true ORR was > 35% (90% power, alpha 0.05). Results: 93 pts (13% of pts screened on S1400) were assigned to S1400D; 43 were enrolled with 28 receiving AZD4547. Pt characteristics: median age 66.3 y (49-88), female (n = 8, 29%), & Caucasian (n = 25; 89%). Biomarker profile: FGFR1 amplification (n = 38; 86%); FGFR3 S249C (n = 4; 9%); FGFR3 amplification (n = 3; 7%); and FGFR3 fusion (n = 2; 5%). Nine pts (26%) had more than one biomarker alteration. The study was closed at interim analysis for futility in October 2016. Treatment related Grade 3 AEs were seen in 5 pts (dyspnea, fatigue, hyponatremia, lung infection & retinopathy); 1 pt had Grade 4 sepsis. There were no Grade 5 AEs. Median follow up among alive pts was 4.3 months (mos). Of 25 response evaluable pts, one with FGFR3 S249C had unconfirmed PR (4%, 95% CI 1-20%) with DoR of 1.5 mos. Median PFS was 2.7 mos (95% CI 1.4 - 4.3 mos). Conclusions: This is the first Phase II trial to evaluate AZD4547 as a targeted approach in pts with previously treated FGFR-altered SqNSCLC. AZD4547 had an acceptable safety profile but minimal activity in this biomarker-enriched cohort. Evaluation of other targeted agents in LUNG-MAP is currently ongoing. Clinical trial information: NCT02965378.

Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study.

2019 ◽  
Vol 37 (18_suppl) ◽  
pp. LBA4007-LBA4007 ◽  
Author(s):  
Josep Tabernero ◽  
Eric Van Cutsem ◽  
Yung-Jue Bang ◽  
Charles S. Fuchs ◽  
Lucjan Wyrwicz ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Final Analysis ◽  
Disease Status ◽  
Phase Iii ◽  
Controlled Study ◽  
Meaningful Improvement ◽  
Primary Endpoints ◽  
Positive Score ◽  
Combined Positive Score ◽  
Grade 3

LBA4007 Background: KEYNOTE062 (NCT02494583) was a randomized, active controlled study of 1L P or P+C vs C in pts with PD-L1 combined positive score ≥1 (CPS ≥1), HER2-negative, advanced GC. Methods: Eligible pts were randomized 1:1:1 to P 200 mg Q3W for up to 2 y, P+C (cisplatin 80 mg/m2 + 5-FU 800 mg/m2/d on d1-d5 Q3W [or capecitabine 1000 mg/m2 BID on d1-d14 Q3W per local guideline]) or placebo Q3W + C. Randomization was stratified by region, disease status, and fluoropyrimidine treatment. Primary endpoints were OS in CPS ≥1 and CPS ≥10 for P+C vs C and P vs C and PFS (RECIST v1.1; central review) in CPS ≥1 for P+C vs C. ORR (RECIST v1.1; central review) in CPS ≥1 for P+C vs C was the secondary endpoint. Final analysis cutoff date was 26 Mar 2019. Results: 763 pts (281 with CPS ≥10) were randomized to P+C (257), P (256), or C (250) (Table). Median follow-up was 11.3 mo. P was noninferior to C for OS in CPS ≥1 per prespecified margins. P vs C prolonged OS in CPS ≥10 (median 17.4 vs 10.8 mo; HR 0.69; 95% CI 0.49-0.97) but wasn’t tested per analysis plan. P+C vs C was not superior for OS in CPS ≥1 or CPS ≥10, with a favorable trend for P+C. P+C did not significantly prolong PFS in CPS ≥1. ORR was higher for P+C vs C. Grade 3-5 drug-related AE rates were 17% (P), 73% (P+C), and 69% (C). Conclusions: As 1L therapy for advanced GC, P was noninferior to C for OS in CPS ≥1 with clinically meaningful improvement for OS in CPS ≥10. P+C did not show superior OS and PFS in CPS ≥1 and OS in CPS ≥10. The safety profile was more favorable for P vs C. Clinical trial information: NCT02494583. [Table: see text]

Update on KEYNOTE-199, cohorts 1-3: Pembrolizumab (pembro) for docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 104-104 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Josep M. Piulats ◽  
Marine Gross-Goupil ◽  
Jeffrey C. Goh ◽  
Ulka N. Vaishampayan ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Response Rate ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Phase 2 Study ◽  
Previously Treated ◽  
Grade 3 ◽  
Clinical Trial Information

104 Background: The KEYNOTE-199 multicohort phase 2 study (NCT02787005) showed that pembro monotherapy has antitumor activity and acceptable safety in patients (pts) with mCRPC previously treated with a next-generation hormonal agent (NHA) and docetaxel in cohort 1 (C1) (RECIST-measurable, PD-L1+ disease), C2 (RECIST-measurable, PD-L1− disease), and C3 (bone-predominant disease, irrespective of PD-L1). Updated results with additional follow-up for C1-3 are presented. Methods: Pts previously received ≥1 NHAs and 1 or 2 chemotherapies, including docetaxel. Pts received pembro 200 mg Q3W for 35 cycles or until progression or intolerable toxicity. Primary end point was ORR. Key secondary end points were DCR, DOR, PSA (≥50%) response rate, rPFS, OS, and safety. Results: Of 258 pts enrolled (C1=133; C2=67; C3=58), 6 completed (C1=4; C3=2) and 252 discontinued (C1=129; C2=67; C3=56) therapy, primarily due to progression (C1=106; C2=61; C3=45). Median follow-up was 9.6 mo (C1, 9.5; C2, 7.9; C3, 14.2). ORR (95% CI) for pts with measurable disease was 6% (2.6-11.5) in C1 and 3% (0.4-10.4) in C2 (Table; includes other efficacy results). Treatment-related AEs of any grade/grade 3-5 occurred in 57%/16% in C1, 60%/15% in C2, and 71%/17% in C3. 1 pt in each cohort died of a treatment-related AE (C1, sepsis; C2, unknown; C3, immune-related pneumonitis). Conclusions: With additional follow-up, pembro monotherapy continued to show antitumor activity and disease control in pts with RECIST-measurable and bone-predominant mCRPC previously treated with both NHA and docetaxel. Pts experienced durable responses. Safety was consistent with the known safety profile of pembro. Clinical trial information: NCT02787005. [Table: see text]

Safety and efficacy of atezolizumab (atezo) in patients (pts) with autoimmune disease (AID): Subgroup analysis of the TAIL study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21628-e21628
Author(s):  
Thomas Newsom-Davis ◽  
Belen Rubio Viqueira ◽  
Delvys Rodriguez-Abreu ◽  
Jorge Alatorre-Alexander ◽  
Hans J.M. Smit ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Phase Iii ◽  
Safety Measures ◽  
Safety And Efficacy ◽  
History Of ◽  
Secondary Endpoints ◽  
Previously Treated ◽  
Pleural Infection ◽  
Ecog Ps

e21628 Background: Atezo showed improved survival and a manageable safety profile in advanced NSCLC. The Phase III/IV TAIL study (NCT03285763) evaluated atezo in pts with previously treated advanced NSCLC, including pts often excluded from pivotal trials. We analyzed outcomes in pts with a history of AID in TAIL. Methods: Pts had stage IIIb/IV NSCLC that progressed after 1-2 lines of chemo and ECOG PS ≤ 2. Eligible pts included those with preexisting AID. Pts received atezo 1200 mg IV q3w. The primary endpoint was safety as measured by the incidence of treatment-related (TR) serious AEs (SAEs) and TR immune-related AEs (irAEs). Secondary endpoints included OS, PFS, ORR and other safety measures. Results: Of the 619 pts enrolled, 615 received atezo, including 30 pts with AID. In AID pts, the median age was 67 y, 43.3% were male and 86.7% had ECOG PS 0-1; common preexisting conditions included psoriasis (n = 7) and rheumatoid arthritis (n = 5). 23 pts had active AID at baseline. At data cutoff (Jun 4 2019), median follow-up was 12.7 mo. TR SAEs occurred in 6.7% and 7.9% of AID vs non-AID pts, respectively; TR irAEs occurred in 10.0% and 8.2% (table). AEs occurring in AID pts at a ≥ 10% difference vs non-AID pts were decreased appetite (26.7%), nausea (26.7%), dyspnea (23.3%) and pneumonitis (13.3%). G3-4 AE incidences were similar between groups (30.0% vs 29.9%). AEs leading to treatment discontinuation occurred in 16.7% and 4.3% of AID vs non-AID pts and included G1-2 pneumonitis (6.7%), G3-4 pleural infection (3.3%) and G3-4 pneumonia (3.3%). AEs of special interest (AESI) occurred more frequently in AID (40.0%) vs non-AID (34.2%) pts, with pneumonitis (13.3% vs 3.1%), rash (13.3% vs 10.6%) and hypothyroidism (6.7% vs 9.6%) as the most common AESIs in either group. Exploratory efficacy analyses in AID vs non-AID pts showed an mOS of 10.1 vs 11.1 mo, an mPFS of 2.9 vs 2.7 mo and ORRs of 10.0% vs 11.1%. Conclusions: Despite the small number of AID pts, safety and efficacy outcomes of atezo in TAIL pts with a history of AID were similar to those of pts with no history of AID. Moderate AE increases seen in AID pts tended to be respiratory in nature or GI disorders. These data may inform treatment decisions in pts with advanced NSCLC and AID. Clinical trial information: NCT03285763. [Table: see text]

Treatment-free survival after discontinuation of immuno-checkpoint therapy, and outcome of subsequent molecular targeted therapy: Retrospective study of Japanese metastatic renal cell carcinoma patients (after I-O study).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 677-677
Author(s):  
Yoshihiko Tomita ◽  
Go Kimura ◽  
Satoshi Fukasawa ◽  
Yutaka Sugiyama ◽  
Kazuyuki Numakura ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Free Survival ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Grade 3

677 Background: Guidelines for treatment of metastatic renal cell carcinoma (mRCC) recommend nivolumab monotherapy (NIVO) for treated mRCC, and nivolumab + ipilimumab combination therapy (NIVO+IPI) for untreated IMDC intermediate and poor risk mRCC patients. Though molecular targeted therapies (TTs) such as VEGFR-TKIs and mTORi are recommended as subsequent therapy after NIVO or NIVO+IPI, their impact is still unclear. Methods: Japanese mRCC patients treated with TT after NIVO (CheckMate 025) or NIVO+IPI (CheckMate 214) were retrospectively analyzed. Primary endpoints were investigator assessed ORR of the first TT after NIVO, and after NIVO+IPI. Secondary endpoints included treatment-free survival (TFS) after discontinuation of NIVO and NIVO+IPI, and progression-free survival (PFS) and safety of the first subsequent TT after NIVO and NIVO+IPI. Results: Twenty-six patients of CheckMate 025 and 19 patients of CheckMate 214 from 20 centers in Japan were analyzed. Median TFS after ICI discontinuation was 1.0m and 2.5m for CheckMate 025 and CheckMate 214 patients, respectively. Median follow-up period from the start of TT after ICI discontinuation to date of analysis or death was 22.1m for CheckMate 025, and 20.3m for CheckMate 214 patients. As the first subsequent TT after NIVO or NIVO+IPI, axitinib was the most treated therapy for both CheckMate 025 (53.8%) and CheckMate 214 (47.4%) patients. ORR of TT after NIVO and NIVO+IPI was 26.9% and 31.6%, and median PFS was 8.9m and 16.3m, respectively. During the treatment of first TT after NIVO and NIVO+IPI, 98% percent experienced treated-related adverse events, 51% experienced grade 3-4, but no treatment related death. Conclusions: TTs have favorable antitumor activity for mRCC after NIVO and NIVO+IPI, possibly by changing the mode of action. Safety signals of TTs after ICI were similar to the previous reports. These results indicate sequential TTs after ICI may contribute for durable survival benefit.

scholarly journals Phase 2 study of ruxolitinib in combination with 5-azacitidine in patients with myelofibrosis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7063-7063 ◽  
Author(s):  
Lucia Masarova ◽  
Jorge E. Cortes ◽  
Naveen Pemmaraju ◽  
Elias Jabbour ◽  
Prithviraj Bose ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Bone Marrow Fibrosis ◽  
Therapy Discontinuation ◽  
Previous Therapy ◽  
Phase 2 Study ◽  
Previously Treated ◽  
Grade 3 ◽  
Clinical Trial Information

7063 Background: Ruxolitinib (RUX) is effective in controlling symptoms and organomegaly in patients with myelofibrosis (MF). Combination with azacitidine (AZA) may further improve its efficacy. Methods: RUX 15 or 20 mg orally twice daily was given continuously since cycle 1. AZA 25 to 75 mg/m2 on days 1-5 of each 28-day cycle was added starting cycle 4. Responses were assessed per International Working Group for Myelofibrosis Research and Treatment 2013 criteria (IWG-MRT). Results: Among 44 pts enrolled between 03/2013 and 06/2016, 39 patients (89%) were evaluable for response. After median (med) follow-up of 20.4+ months (range, 0.5-37+); 24 pts (54%) are on study with a med overall survival of 39+ months. Med age was 66 years (range, 48-87), 36 pts (82%) had int-2/high IPSS score, 29 (66%) had spleen ≥5cm, and 24 (55%) were JAK2 V617F positive. Twenty five pts (57%) were previously treated. Twenty eight (72%) pts had objective response regardless of previous therapy (Table). Med time to response was 1.0 months. 7 (25%) responses occurred after the addition of AZA with med time to response of 4.2 months. In total, 23 pts (79%) had palpable spleen reduction by > 50%, which occurred after AZA was added in 6 (28%) of them. JAK2V617Fallele reduction was noted in 13 (87%) evaluable pts, including > 50% reduction in 3 pts (13%). A reduction in bone marrow fibrosis grade was observed in 12 (31%) responders, including ≥2 and 1 grade reduction in 2 and 9 pts, respectively. Grade 3/4 non-hematological and hematological toxicities occurred in 4 and 16 pts, respectively. The most common reasons for therapy discontinuation (n=17) were stem cell transplantation (n=6), lack of response (n=3) and progression to AML (n=2). Conclusions: Concomitant RUX with AZA was feasible with overall IWG-MRT response rate of 72%, including >50% spleen reduction in 79% of patients, which compares favorably to single RUX. Clinical trial information: NCT01787487. [Table: see text]

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