Pembrolizumab (pembro) for advanced biliary adenocarcinoma: Results from the KEYNOTE-028 (KN028) and KEYNOTE-158 (KN158) basket studies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4079-4079 ◽  
Author(s):  
Yung-Jue Bang ◽  
Makoto Ueno ◽  
David Malka ◽  
Hyun Cheol Chung ◽  
Adnan Nagrial ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Phase 1 ◽  
Treatment Options ◽  
Inflammatory Cells ◽  
Infusion Reaction ◽  
Positive Staining ◽  
Treatment Regimens ◽  
Grade 5 ◽  
Ecog Ps

4079 Background: Antitumor activity with pembro, an anti–PD-1 antibody, has been observed in patients (pts) with advanced/metastatic biliary tract cancers (BTC), who have limited treatment options. We present follow-up data from pts with advanced BTC treated with pembro in the KN158 (NCT02628067; phase 2) and KN028 (NCT02054806; phase 1) studies. Methods: Eligible pts ≥18 y in the KN158/KN028 BTC cohorts had histologically/cytologically confirmed incurable advanced BTC that progressed after/failed any number of prior standard treatment regimens, measurable disease per RECIST v1.1, ECOG PS of 0/1, and no prior immunotherapy. PD-L1–positivity (membranous PD-L1 expression in ≥1% of tumor and associated inflammatory cells or positive staining in stroma) was required for eligibility in KN028, but not KN158. Pts received pembro 200 mg Q3W (KN158) or 10 mg/kg Q2W (KN028) for up to 2 y. Radiographic imaging occurred Q9W for 12 mo (KN158) or Q8W for 6 mo (KN028) and Q12W thereafter. Primary efficacy endpoint in both studies was ORR by RECIST 1.1. Response assessed by independent central review is reported. Results: Median (range) follow-up was 7.5 (0.6–29.5) mo in the 104 pts from KN158 and 6.5 (0.6–33.1) mo in the 24 pts from KN028 with BTC. All pts in KN028 and 61 in KN158 had PD-L1–positive tumors. No pt had MSI-H tumors (not assessed in KN028). In KN158, ORR was 5.8% (6/104, all PR [including 1 pt with PD-L1–negative tumor]; 95% CI, 2.1%–12.1%) and median duration of response (DOR) was not reached (NR; range, 6.2 to 23.2+ mo). Median OS and PFS were 7.4 mo (95% CI, 5.5–9.6) and 2.0 mo (95% CI, 1.9–2.1). 12-mo OS rate was 32.7%. In KN028, ORR was 13.0% (3/23, all PR; 95% CI, 2.8%‒33.6%) and median DOR was NR (range, 21.5 to 29.4+ mo). Median OS and PFS were 6.2 mo (95% CI, 3.8‒10.3) and 1.8 mo (95% CI, 1.4‒3.7), respectively. 12-mo OS rate was 27.6%. Grade 3–5 treatment-related AEs occurred in 13.5% in KN158 (1 pt had grade 5 renal failure) and 16.7% of pts in KN028 (no grade 5). 18.3% in KN158 and 20.8% of pts in KN028 had an immune-mediated AE or infusion reaction. Conclusions: Pembro provides durable antitumor activity, regardless of PD-L1 expression, and manageable toxicity in a subset of pts with advanced BTC. Clinical trial information: NCT02054806 and NCT02628067.

Phase 2 study of pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer (mTNBC): Preliminary data from KEYNOTE-086 cohort B.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1088-1088 ◽  
Author(s):  
Sylvia Adams ◽  
Sherene Loi ◽  
Deborah Toppmeyer ◽  
David W. Cescon ◽  
Michele De Laurentiis ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Imaging ◽  
Treatment Options ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
New Treatment ◽  
Combined Positive Score ◽  
Ecog Ps

1088 Background: Standard first-line treatment for mTNBC is chemotherapy. However, outcomes are poor, and new treatment options are needed. Cohort B of KEYNOTE-086 (NCT02447003) assessed the safety and antitumor activity of pembrolizumab as first-line therapy for patients (pts) with PD-L1–positive mTNBC. Methods: Men and women with centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, ECOG PS 0-1, and a tumor PD-L1 combined positive score (CPS) ≥1% received pembrolizumab 200 mg Q3W for 24 mo or until disease progression, intolerable toxicity, or investigator or pt decision. Tumor imaging was performed Q9W for 12 mo and Q12W thereafter. Clinically stable pts with PD could remain on pembrolizumab until PD was confirmed on subsequent assessment. Primary end point was safety. Secondary end points included ORR, DOR, and PFS (RECIST v1.1, central review). Planned enrollment was 80 pts. This analysis included all pts who had ≥18 wk of follow-up as of Nov 10, 2016. Results: 79 of the first 137 pts with PD-L1–evaluable tumors (58%) had PD-L1 CPS ≥1%. Of the first 52 pts enrolled, 100% were women, median age was 53 y, 40% had elevated LDH, 69% had visceral metastases, and 87% received prior (neo)adjuvant therapy. After a median follow-up of 7.0 mo (range 4.4-12.5), 15 (29%) pts remained on pembrolizumab. Treatment-related AEs occurred in 37 (71%) pts, most commonly fatigue (31%), nausea (15%), and diarrhea (13%). 4 (8%) pts experienced 5 grade 3-4 treatment-related AEs: back pain, fatigue, hyponatremia, hypotension, and migraine (n = 1 each). No pts died or discontinued pembrolizumab due to an AE. ORR was 23% (95% CI 14%-36%). Best overall response was CR in 4%, PR in 19%, SD in 17%, PD in 58%, and not assessed in 2%. Median time to response was 8.7 wk (range 8.1-17.7). Median DOR was 8.4 mo (range, 2.1+ to 8.4), with 8 (67%) responses ongoing at cutoff. Median PFS was 2.1 mo (95% CI, 2.0-3.9); estimated 6-mo PFS rate was 29%. Conclusions: Data from the first 52 pts enrolled in KEYNOTE-086 cohort B suggest that pembrolizumab monotherapy has a manageable safety profile and promising antitumor activity as first-line therapy for PD-L1–positive mTNBC. Clinical trial information: NCT02447003.

KEYNOTE-029: Efficacy and safety of pembrolizumab (pembro) plus ipilimumab (ipi) for advanced melanoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9545-9545 ◽  
Author(s):  
Matteo S. Carlino ◽  
Victoria Atkinson ◽  
Jonathan S. Cebon ◽  
Michael B. Jameson ◽  
Bernie M. Fitzharris ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Standard Dose ◽  
Phase 1 ◽  
Advanced Melanoma ◽  
Prior Therapy ◽  
Immune Mediated ◽  
Grade 3 ◽  
Expansion Cohort ◽  
Ecog Ps

9545 Background: We previously showed that standard-dose pembro plus reduced-dose ipi has manageable safety and robust antitumor activity in patients (pts) with advanced melanoma. Here, we present more mature data, including 1-y landmark PFS and OS estimates. Methods: In the phase 1 KEYNOTE-029 expansion cohort (NCT02089685), pts with advanced melanoma, ECOG PS 0-1, no active brain metastases, and no prior immune checkpoint inhibitor therapy received pembro 2 mg/kg Q3W + ipi 1 mg/kg Q3W for 4 doses, then pembro alone for up to 2 y. Primary end point was safety. Efficacy end points were ORR, PFS, and DOR per RECIST v1.1 by independent central review and OS. Results: 153 pts were enrolled between Jan 13, 2015, and Sep 17, 2015. Median age was 60 y, 66% were male, 25% had elevated LDH, 56% had stage M1c disease, 36% were BRAFV600mutant, and 13% received ≥1 prior therapy. As of Oct 17, 2016, median follow-up was 17 mo, and 64 (42%) pts remained on pembro. 110 (72%) pts received all 4 ipi doses. There were no treatment-related (TR) deaths. TRAEs occurred in all pts, were grade 3/4 in 69 (45%), and led to discontinuation of pembro and ipi in 17 (11%), ipi alone in 11 (7%), and pembro alone after ipi completion or discontinuation in 19 (12%). PD occurred in 1/11 pts who discontinued ipi alone and 4/17 pts who discontinued ipi and pembro. Of the 11 pts who discontinued ipi alone for a TRAE, 0 experienced recurrence of the same TRAE during pembro monotherapy and 2 discontinued pembro for a different TRAE (both elevated lipase). Immune-mediated AEs occurred in 90 (59%) pts and were grade 3/4 in 39 (25%). With 7 mo additional follow-up, there were 6 additional responses for an ORR of 61% (95% CI, 53%-69%); the CR rate increased from 10% to 15%. Median DOR was not reached (range, 1.6+ to 18.1+ mo), with 86/93 responders (92%), including 23/23 (100%) with CR, alive and without subsequent PD at cutoff. Median PFS and OS were not reached; 1-y estimates were 69% for PFS and 89% for OS. Conclusions: Pembro 2 mg/kg plus 4 doses of ipi 1 mg/kg has a manageable toxicity profile and provides robust, durable antitumor activity in pts with advanced melanoma. Clinical trial information: NCT02089685.

Pembrolizumab in patients (pts) with PD-L1–positive (PD-L1+) advanced ovarian cancer: Updated analysis of KEYNOTE-028.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5513-5513 ◽  
Author(s):  
Andrea Varga ◽  
Sarina Anne Piha-Paul ◽  
Patrick Alexander Ott ◽  
Janice M. Mehnert ◽  
Dominique Berton-Rigaud ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Antitumor Activity ◽  
Advanced Ovarian Cancer ◽  
Inflammatory Cells ◽  
Complete Response ◽  
Positive Staining ◽  
Eligibility Criteria ◽  
Prior Therapy ◽  
Best Response

5513 Background: Overexpression of the PD-1 ligand PD-L1 has been demonstrated in ovarian cancer and may hinder an effective antitumor immune response. A preliminary analysis of the ovarian cancer cohort of the KEYNOTE-028 study (NCT02054806) suggested that the PD-1 inhibitor pembrolizumab has promising antitumor activity in pts with PD-L1+advanced ovarian cancer. An updated analysis of the ovarian cancer cohort based on 15.5 months of follow-up is presented. Methods: Key eligibility criteria for the ovarian cohort of this nonrandomized, multicohort phase Ib trial were advanced ovarian epithelial, fallopian tube, or primary peritoneal carcinoma; failure of prior therapy; PD-L1 positivity defined as membranous staining on ≥1% of tumor and associated inflammatory cells or positive staining in stroma; and ECOG PS 0/1. Pembrolizumab (10 mg/kg every 2 wk) was given for ≤2 y or until confirmed progression/unacceptable toxicity. Response was assessed per RECIST v1.1 by investigators every 8 wk for the first 6 mo and every 12 wk thereafter. Primary end points were safety, tolerability, and confirmed ORR. Results: 26 pts (median age, 57.5 y) were enrolled; 61.5% were white, 38.5% received ≥5 therapies for recurrent/metastatic disease, and 53.8% received prior neoadjuvant/adjuvant therapies. As of the October 10, 2016, data cutoff, the median follow-up duration was 15.5 mo (range, 2.4-30.8 mo). 1 pt had a complete response and 2 had partial responses; 6 pts had stable disease as best response. ORR was 11.5% (95% CI, 2.4%-30.2%). Tumor reduction was observed in 6/26 (23.1%); all 3 patients who responded completed 2 years of treatment. Median duration of response was not reached (range, 24.9+ to 26.5+ mo). Median (95% CI) PFS and OS were 1.9 mo (1.8-3.2 mo) and 13.1 mo (6.7-17.5 mo) respectively. Treatment-related AEs occurred in 73.1% of pts, and the most common were arthralgia (19.2%), nausea (15.4%), pruritus (15.4%), rash (11.5%), and diarrhea (11.5%). 1 patient had a grade 3 drug-related adverse event (transaminase increased). Conclusions: With 15.5 mo of follow-up, pembrolizumab continued to be well tolerated and demonstrated durable antitumor activity in pts with advanced ovarian cancer. Clinical trial information: NCT02054806.

Antitumor activity of dostarlimab in patients with mismatch repair-deficient/microsatellite instability–high tumors: A combined analysis of two cohorts in the GARNET study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2564-2564
Author(s):  
Dominique Berton ◽  
Susana N. Banerjee ◽  
Giuseppe Curigliano ◽  
Sara Cresta ◽  
Hendrik-Tobias Arkenau ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Solid Tumors ◽  
Phase 1 ◽  
Objective Response ◽  
Low Grade ◽  
Open Label ◽  
Tumor Types

2564 Background: Dostarlimab is an investigational, humanized programmed death 1 (PD-1) receptor monoclonal antibody that blocks interaction with the PD-1 ligands, PD-L1 and PD-L2. GARNET (NCT02715284) is a phase 1 study assessing the antitumor activity and safety of dostarlimab monotherapy in patients with solid tumors. Methods: This multicenter, open-label, single-arm study is being conducted in 2 parts: dose escalation and expansion. Here we report on the 2 expansion cohorts that enrolled mismatch repair–deficient/microsatellite instability–high (dMMR/MSI-H) patients. Cohort A1 enrolled patients with advanced or recurrent dMMR/MSI-H endometrial cancer (EC), and cohort F enrolled patients with advanced or recurrent dMMR/MSI-H or POLε-hypermutated non-EC solid tumors, mainly gastrointestinal (GI) tumors (99 [93.4%] had GI tumors, including 69 [65.1%] with colorectal cancer). Patients received 500 mg IV of dostarlimab every 3 weeks for 4 cycles, then 1000 mg IV every 6 weeks until disease progression or discontinuation. The primary endpoints were objective response rate (ORR) and duration of response (DOR) by RECIST v1.1. Here we report ORR and DOR, by individual cohort and as an overall population, in patients with dMMR tumors identified by immunohistochemistry testing. Results: For this interim analysis, an efficacy analysis was performed for the patients who had baseline measurable disease and ≥6 months of follow-up in the study (N = 209). The ORR was 41.6% (95% CI, 34.9%–48.6%) for the combined A1+F dMMR cohorts (Table). Responses were durable, and median DOR has not been reached in either cohort (median follow-up: cohort A1, 16.3 months; cohort F, 12.4 months). A total of 267 patients were included in the safety population (all patients who received ≥1 dose; cohort A1, N = 126; cohort F, N = 141). Treatment-related adverse events (TRAEs) were consistent across tumor types. Overall, the most frequently reported any-grade TRAEs were asthenia (13.9%), diarrhea (13.5%), and fatigue (11.2%). The most common grade ≥3 TRAEs were anemia (2.2%), lipase increased (1.9%), alanine aminotransferase increased (1.1%), and diarrhea (1.1%). No deaths were attributed to dostarlimab. Conclusions: Dostarlimab demonstrated durable antitumor activity in patients with dMMR solid tumors, with consistent antitumor activity seen across endometrial and nonendometrial tumor types. The safety profile was manageable, with no new safety signals detected. Most TRAEs were low grade and were similar across cohorts. Clinical trial information: NCT02715284. [Table: see text]

Bladder cancer

2019 ◽  
Vol 13 (6) ◽  
pp. 271-277
Author(s):  
Ian Peate
Keyword(s):  
Bladder Cancer ◽  
Treatment Options ◽  
Older Person ◽  
Multiple Choice Questions ◽  
Men And Women ◽  
Treatment Regimens ◽  
Common Cancer ◽  
The One ◽  
The Uk

This article is the one in the cancer series that discusses bladder cancer. Bladder cancer can occur in men and women; however, in the UK, there are more men with bladder cancer than women. It is also a disease of the older person. This article provides an introduction that discusses the condition. An overview of the anatomy of the bladder and ureters is provided. In 2015, bladder cancer was the 10th most common cancer in the UK and was responsible for 3% of all new cancer cases. Diagnosis and treatment options are discussed, with an emphasis on ensuring that the patient is key in any decisions that are made about treatment regimens. The importance of follow-up after treatment is also discussed. A glossary of terms is provided and five multiple-choice questions are included to enhance learning and application to practice.

Phase I results from a phase I/II study of orteronel, an oral, investigational, nonsteroidal 17,20-lyase inhibitor, with docetaxel and prednisone (DP) in metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4656-4656 ◽  
Author(s):  
Daniel Peter Petrylak ◽  
Jitendra G. Gandhi ◽  
William R. Clark ◽  
Elisabeth I. Heath ◽  
Jianqing Lin ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Phase I ◽  
Phase 1 ◽  
Infusion Reaction ◽  
Primary Phase ◽  
Castration Resistant Prostate Cancer ◽  
Investigational Agent ◽  
Group 2 ◽  
Wbc Count ◽  
Ecog Ps

4656 Background: The investigational agent orteronel (ortl, TAK-700) is a selective 17,20-lyase inhibitor that blocks androgen production. Since DP is standard chemotherapy in mCRPC, this phase 1/2 study examined ortl + DP in men with mCRPC. Methods: The primary phase I objective was to determine the maximum dose of ortl 200–400 mg BID that can be administered safely with DP in castrate men (testosterone [T] <50 ng/dL) with mCRPC, ≤1 prior chemotherapy and no ketoconazole/abiraterone ≤30 d prior. A 3+3 dose escalation was used with ortl 200 then 400 mg BID. Ortl dosed daily and D (75 mg/m2 q3w) + P (5 mg BID) was started on d8 of cycle 1 (28 d); cycles ≥2 = 21 d. Results: 14 men, median age 68 yrs (range 53–81), ECOG PS 0/1 (71%/29%), median PSA 59.4 ng/mL (5.2–1052), T 8.1 ng/dL (1.2–16.7), 9 with measurable disease, were treated. Median ortl exposure was 33.3 wks (6.3–59); 6 and 8 men received ortl 200 and 400 mg BID + DP, in cohorts 1 and 2, respectively. No dose-limiting toxicities (DLTs) occurred in cohort 1 (2 x 3 pts); in cohort 2 (2 x 4 pts), 1 pt in group 1 had DLT (Gr3 related febrile neutropenia); no DLTs occurred in group 2. 3 pts discontinued due to AEs (2 D infusion reactions, 1 at each dose; 1 unrelated cardiorespiratory death at 200 mg). All men had at least 1 AE Gr ≥3 which were treatment-related in 11 men. The most common Gr ≥3 AEs were seen at both doses and included neutropenia 50% (n = 7), hyperglycemia 21% (n = 3), febrile neutropenia, infusion reaction, hyponatremia, decreased neutrophil count (2 each); at 400 mg only: fatigue, hypophosphatemia, and decreased WBC count (2 each). 7 men had serious AEs (SAEs), which were drug-related in 5. The most common SAE was febrile neutropenia in 2 men. At 3 mo, PSA50 and PSA90 rates were 86% and 36%, respectively; 12/14 men had a median PSA decline ≥70%; and median T declined to ≤0.2 ng/dL (0–10.7). The Cmax of D + ortl was similar to D alone. Conclusions: Ortl 200 mg and 400 mg BID + DP appears safe and tolerable with androgen-lowering activity at the maximum planned dose in mCRPC. There is no evidence of AE potentiation when ortl is administered with DP. The phase II portion of the study will use ortl 400 mg BID + DP.

Pilot study combining PD-L1 antibody durvalumab (D) with CTLA-4 antibody tremelimumab (T) and stereotactic body radiotherapy (SBRT) to treat metastatic anaplastic thyroid cancer (ATC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6088-6088 ◽  
Author(s):  
Eric Jeffrey Sherman ◽  
C. Jillian Tsai ◽  
Wanqing Iris Zhi ◽  
James Vincent Fetten ◽  
Vanessa Wu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Options ◽  
Inflammatory Cells ◽  
Anaplastic Thyroid Cancer ◽  
P53 Mutation ◽  
Primary Objective ◽  
The Body ◽  
Aggressive Cancer ◽  
Anti Cancer ◽  
Ecog Ps

6088 Background: ATC is a rare and aggressive cancer with very limited treatment options. The thyroid is one of the most immunogenic organs in the body and PD-L1 is commonly expressed on ATC tumor cells and PD-1 in the inflammatory cells in the ATC microenvironment. However, antibodies to PD-1 as single agents have a poor record in this disease. Methods: This study evaluated the addition of T (75 mg every 4 weeks up to 4 doses) to D (1500 mg every 4 weeks). SBRT 9Gy x 3 fractions was given within the first 2 weeks of treatment to produce an “abscopal” effect. Major inclusion criteria: Metastatic ATC; ECOG PS 0-2; No prior immunotherapy; Last anti-cancer treatment > 7 days prior to starting study. Primary objective 1-year overall survival with target of ≥ 2 out of 12 patients. Results: 12 patients were accrued. Male – 50%; Median PS 1; Median Age – 71 (49-82); Prior radiation to neck (75%); Prior chemotherapy (75%). MSI-High was noted in 2/11 subjects. BRAFV600E mutation in 3/12 subjects. There were 0 confirmed responses and only 1 subject with SD for 4 cycles or longer. Median time on treatment was 11 weeks (1-28+ weeks). MSI status did not affect treatment response. MSI-High patients were on treatment before progression for 8-14 weeks. Median overall survival was 14.5 weeks with only one person alive past 1 year. Neither the presence of a BRAF or p53 mutation appeared to affect either outcome. Conclusions: T/D with SBRT was not active in metastatic ATC. Future studies looking at other novel immunotherapy combinations in ATC should be evaluated. Biopsies done on study are being analyzed. Clinical trial information: NCT03122496.

Safety and clinical activity of durvalumab monotherapy in patients with microsatellite instability–high (MSI-H) tumors.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 670-670 ◽  
Author(s):  
Neil Howard Segal ◽  
Zev A. Wainberg ◽  
Michael J. Overman ◽  
Paolo Antonio Ascierto ◽  
Hendrik-Tobias Arkenau ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Median Duration ◽  
Multicenter Study ◽  
Phase 1 ◽  
Objective Response ◽  
Clinical Activity ◽  
Single Center ◽  
Single Center Study ◽  
Center Study

670 Background: MSI-H tumors have shown to be responsive to PD-1 inhibitor therapy. We evaluated the anti-PD-L1 mAb durvalumab in patients with MSI-H tumors, in two ongoing studies: a phase 1/2, multicenter, open-label study in patients with advanced solid tumors, and a phase 2 single-center study in patients with advanced colorectal cancer (CRC). Methods: Patients with MSI-H tumors (determined locally by immunohistochemistry or sequencing) received durvalumab 10 mg/kg IV every 2 weeks for 12 months or until confirmed progressive disease, whichever was first. Objectives were to evaluate safety and antitumor activity (per investigator-assessed RECIST v1.1). Results: As of Oct 16, 2017, 62 MSI-H patients (97% with prior anti-cancer therapy) received treatment in the multicenter study; median duration of follow-up was 29 months. Treatment-related adverse events (TRAEs) occurred in 37 patients (60%), most commonly diarrhea (15%), asthenia (11%), fatigue (11%), nausea (10%), and hypothyroidism (10%). Grade 3/4 TRAEs occurred in 2 patients (3%). There were no deaths or treatment discontinuations due to TRAEs. Objective response rates (ORR) were 23% for the total population and 22% for patients with CRC; 9 of 14 responders were ongoing at data cutoff. As of Sep 13, 2018, 11 patients with MSI-H CRC were treated in the single-center study; median duration of follow-up was 30 months. One patient discontinued treatment due to treatment-related aseptic meningitis (resolved with steroids); response rate and survival were similar to the multicenter study (Table). Conclusions: Durvalumab had a tolerable safety profile, and showed promising antitumor activity and overall survival in patients with MSI-H tumors. Clinical trial information: NCT01693562 and NCT02227667. [Table: see text]

A randomized phase II trial comparing switch to nivolumab with TKI continuation after 12 weeks of TKI induction therapy in metastatic renal cell carcinoma patients (NIVOSWITCH).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 678-678 ◽  
Author(s):  
Viktor Grünwald ◽  
Carsten Grüllich ◽  
Philipp Ivanyi ◽  
Manfred Wirth ◽  
Peter Staib ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Premature Closure ◽  
Randomized Phase Ii ◽  
Safety Population ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
Ecog Ps

678 Background: Tyrosine kinase inhibitors (TKI) and Nivolumab (NIVO) are standard treatment options for mRCC. We tested whether TKI followed by early switch to NIVO improved outcome in mRCC patients (pts). Methods: Main inclusion criteria: measurable advanced or metastatic clear cell RCC, ECOG PS 0-2, adequate organ function, PR or SD to induction therapy with sunitinib (50 mg, 4-2 regime) or pazopanib (800 mg OD). 1:1 randomization at 12 wks.: TKI continuation vs. switch to NIVO (240 or 480 mg IV q2-4wks). Strata were MSKCC risk, TKI used and response to TKI. Imaging was performed q12w. 49 of 244 planned pts were randomized between Dec 2016 and Aug 2018, which led to premature closure of the trial. We report the second interim analysis with data base lock on 31.07.19. ORR was assessed according to RECIST 1.1. Efficacy and safety analyses were performed in ITT and safety population, respectively. Log-Rank analyses were used for survival analyses. Results: 25 and 24 pts received NIVO or TKI, respectively. Median age was 65 y (range: 35-79), 82% were male and 4% had ECOG PS 2. Metastases occurred predominantly in lung (47%), lymph nodes (27%) and liver (24%). MSKCC risks were: favorable (31%), intermediate (65%), and poor (4%), which were balanced between arms. 55% received sunitinib. ORR for NIVO vs. TKI differed when assessed from start of induction therapy (64 vs. 70%, P=0.76) or from time of randomization (16 vs. 48%; P=0.032). Accordingly, PFS from randomization was 3.0 vs. 11.9 mo. (HR = 1.72 [95% CI: 1.19 – 2.48]; P=0.0026) in favor of TKI continuation. At a median follow-up of 12.9 mo. median OS was not reached, but HR = 1.86 (95% CI: 0.85 – 4.07) P=0.10 showed a trend for TKI continuation. All grades AE for NIVO vs. TKI occurred in 96% vs. 100%, grade 3-5 48% vs. 71% and serious AE 40% vs. 46%. Conclusions: In TKI-sensitive pts, continuation of TKI is more efficacious than early switch to NIVO. The major limitation of our trial is the premature closure and its limited sample size. Clinical trial information: NCT02959554.

Phase II trial of bevacizumab, gemcitabine, oxaliplatin in patients with metastatic pancreatic adenocarcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4553-4553 ◽  
Author(s):  
G. P. Kim ◽  
A. L. Oberg ◽  
N. R. Foster ◽  
A. Jaslowski ◽  
P. J. Flynn ◽  
...  
Keyword(s):  
Adverse Events ◽  
Median Survival ◽  
Phase Ii ◽  
Grade 5 ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Targeted Agent ◽  
Patient Refusal ◽  
Ecog Ps ◽  
Historical Controls

4553 Background: The combinations of gemcitabine and oxaliplatin (GemOx) and bevacizumab and gemcitabine have activity in pancreatic cancer. Based on these observations, the NCCTG initiated a multicenter phase II study to evaluate the combination of an active cytotoxic doublet and a targeted agent to determine whether improvement in 6-month survival in previously untreated patients with metastatic pancreas cancer could be achieved. Methods: Treatment consists of gemcitabine 1000 mg/m2 IV over 100 minutes and bevacizumab 10 mg/kg IV given on day 1, 15; oxaliplatin 100 mg/m2 IV is given on day 2, 16, repeated every 28 days. Eligibility includes: no prior chemotherapy, ECOG PS 0–2, bili< 2x UNL, AST< 5x UNL. Pts with stable full dose anticoagulation are eligible. Bevacizumab specific exclusions include no recent stroke, heart attack, embolus, tumor invasion or significant proteinuria. CT scans are obtained every 2 cycles. Treatment continues until disease progression, severe adverse events (AEs), or patient refusal. Results: Eighty-two patients were enrolled from 7/05 to 2/06. Median age was 63 (range: 32 - 86). 24 of 82 (29%) evaluable pts had a maximum grade ≥ 4 AE (at least possibly related to treatment). Grade 4 events included (% of pts): neutropenia (7%), thrombosis (6%), thrombocytopenia (5%), pneumonitis (2%), ischemia-cerebral (1%), abdominal infection (1%), small intestine perforation (1%), and small bowel leak (1%). Three patients died from grade 5 events (1-gastric perforation, 1-cerebral ischemia, 1-multi-organ failure). 80 patients were evaluable for outcome assessment (excludes 2 ineligible cases). Median follow-up was 10.3 months (range: 6.3 - 14.7) in the 19 patients still alive. 6-month survival was 65.0% (95% CI: 53.5% - 75.3%). Median survival was 8.1 months (95% CI: 6.5 - 9.3) and median TTP was 5.7 months (95% CI: 4.4 - 6.4). The confirmed response rate was 11.3% (95% CI: 5.3 - 20.3%) with 1 complete and 8 partial responses. Conclusions: In this multi-centered, cooperative group study, promising efficacy with this three-drug combination was observed especially in regards to six- month and median survival. The observed adverse events are comparable to historical controls although caution should be exercised in light of the three grade 5 events. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document