Pembrolizumab for the treatment of patients with high-risk (HR) non-muscle-invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guérin: Extended follow-up of KEYNOTE-057 cohort A.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 451-451
Author(s):  
Arjun Vasant Balar ◽  
Ashish M. Kamat ◽  
Girish S. Kulkarni ◽  
Edward M. Uchio ◽  
Joost L. Boormans ◽  
...  
Keyword(s):  
Complete Response ◽  
Disease Assessment ◽  
Intravesical Therapy ◽  
Bacillus Calmette Guerin ◽  
Primary Analysis ◽  
Open Label ◽  
Efficacy Analysis ◽  
Grade 3 ◽  
Cutoff Date

451 Background: Pembrolizumab (pembro) was approved in January 2020 for treatment of HR NMIBC based on interim results from 96 patients (pts) in the open-label, single-arm, multicenter, phase II KEYNOTE-057 (NCT02625961) study. Here we present updated efficacy and safety results with extended minimum follow-up of 26.3 mo from KEYNOTE-057 cohort A. Methods: Pts aged ≥18 years with histologically confirmed Bacillus Calmette-Guérin (BCG)–unresponsive HR carcinoma in situ (CIS), with or without papillary tumors, who were ineligible for or declined radical cystectomy (RC) received pembro 200 mg Q3W for up to 24 mo or until disease persistence, recurrence, progression, or unacceptable toxicity. Primary end point: complete response rate (CRR). Key secondary end points: duration of response (DOR) and safety. Results: Overall, 101 pts received pembro and 96 were included in the efficacy analysis (5 patients did not meet BCG-unresponsive criteria). Median age was 73 years (range, 44-92), and pts received a median of 12.0 (range, 7.0-45.0) BCG instillations. Median time from enrollment to data cutoff date of May 25, 2020, was 36.4 mo (range, 26.3-48.5). Of 96 pts, CRR was 40.6% (95% CI, 30.7-51.1) at first evaluable disease assessment, and median DOR was 16.2 mo (range, 0.0+ to 36.2). Of 39 responders, 13 (33.3%) remained in CR ≥18 mo and 9 (23.1%) remained in CR ≥24 mo as of the data cutoff date. No pt progressed to MIBC while on study treatment based on protocol-specified disease assessments. CRR was generally consistent with the primary analysis across protocol-prespecified subgroups, including PD-L1 expression status. Forty pts (41.7%) underwent RC after discontinuation of pembro; 35 pts (88%) had no pathologic upstaging to MIBC, 2 (5%) had no available pathology data, and 3 (8%) had evidence of MIBC (all nonresponders); 1 pt had pT2N0 disease at 60 days after the last pembro dose, 1 pt had pT2N1 disease (involvement of a single perivesical lymph node) at 86 days after the last pembro dose, and 1 pt had pT3N1 disease at 457 days after the last pembro dose. For other subsequent treatments, 30 of 96 pts (31.3%) received additional intravesical therapy (eg, BCG), 27 of 96 (28.1%) underwent local procedures (eg, TURBT), and 10 of 96 (10.4%) received systemic therapy. In 101 pts, treatment-related AEs (TRAEs) occurred in 67 pts (66.3%); most frequent were diarrhea, fatigue, and pruritus (10.9% each). Grade 3/4 TRAEs occurred in 13 pts (12.9%). Twenty-two pts (21.8%) experienced immune-related AEs; 3.0% were grade 3-4. Seven pts (6.9%) discontinued due to TRAEs. There were no grade 5 TRAEs. Conclusions: With extended follow-up, pembro continued to show durable and clinically meaningful activity in pts who had HR BCG-unresponsive CIS with or without papillary tumors and who were ineligible for or declined RC. No new safety risks were identified. Clinical trial information: NCT02625961.

scholarly journals 354 Lenvatinib and pembrolizumab in advanced endometrial carcinoma (EC): long-term efficacy and safety update from a phase 1b/2 study

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A381-A381
Author(s):  
Vicky Makker ◽  
Carol Aghajanian ◽  
Allen Cohn ◽  
Margarita Romeo ◽  
Raquel Bratos ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Center ◽  
Efficacy And Safety ◽  
Open Label ◽  
Phase 3 ◽  
Efficacy Analysis ◽  
Phase 1B ◽  
Grade 3 ◽  
Cutoff Date

BackgroundLenvatinib is a multikinase inhibitor of VEGFR 1–3, FGFR 1–4, PDGFRα, RET, and KIT. Pembrolizumab is an anti-programmed death-1 monoclonal antibody. We previously reported results from a cohort of 108 patients with metastatic EC (data cutoff date, January 10, 2019) who received lenvatinib + pembrolizumab as part of an ongoing multicenter, open-label, phase 1b/2 study evaluating the combination treatment in patients with selected solid tumors (NCT02501096). Lenvatinib + pembrolizumab showed a tolerable safety profile and promising antitumor activity per immune-related (ir) Response Evaluation Criteria In Solid Tumors (RECIST) by investigator assessment, including an objective response rate (ORR) of 38.9% (95% confidence interval [CI], 29.7–48.7), median progression-free survival (PFS) of 7.4 months (95% CI, 5.3–8.7), and median overall survival (OS) of 16.7 months (95% CI, 15.0-not estimable).1 Here we present updated efficacy and safety data (data cutoff date: August 18, 2020).MethodsPatients included in the EC cohort had histologically confirmed, measurable metastatic EC and had received ≤2 prior chemotherapies (unless discussed with the sponsor). Patients received lenvatinib (20 mg orally once daily) and pembrolizumab (200 mg intravenously once every 3 weeks). The phase 2 efficacy endpoints included ORR, PFS, OS, and duration of response. Tumor assessments for primary and secondary endpoints were evaluated by investigators per irRECIST.ResultsThe 108 patients from the key efficacy analysis set for the previously reported results were all included in these updated analyses. Median follow-up duration for the study was 34.7 months. Efficacy outcomes are summarized in table 1. Treatment-related adverse events (TRAEs) occurred in 104 (96%) patients (94 [87%] grade ≤3, 10 [9%] grade ≥4). TRAEs led to study-drug interruption of 1 or both drugs in 80 (74.1%) patients and dose reductions of lenvatinib in 73 (67.6%) patients; 23 (21.3%) patients discontinued 1 or both drugs due to a TRAE. The most common grade ≥3 TRAEs were hypertension (33.3%), lipase increased (9.3%), fatigue (8.3%), and diarrhea (7.4%).Abstract 354 Table 1ConclusionsWith extended follow-up, our updated efficacy analysis continued to show clinical benefit in patients with metastatic EC who received lenvatinib + pembrolizumab. Moreover, the combination had a manageable safety profile that was generally consistent with the established safety profiles of the individual monotherapies. No new safety signals were detected. A phase 3 study of lenvatinib + pembrolizumab versus treatment of physician’s choice in advanced endometrial cancer further supports the lasting clinical benefits observed in our study.2Trial Registration www.clinicaltrials.gov NCT02501096ReferencesMakker V, Taylor MH, Aghajanian C, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer. J Clin Oncol 2020;38(26):2981–2992.Makker V, Colombo N, Casado Herráez A, et al. A multicenter, open-label, randomized, phase 3 study to compare Ethics ApprovalThis study was approved by the following ethics committees/institutional review boards (IRBs): Oregon Health & Sciences University IRB, IntegReview IRB, Memorial Sloan Kettering Cancer Center IRB, University of Pennsylvania Office of Regulatory Affairs IRB, Dana-Farber Cancer Institute IRB, The University of Chicago Biological Sciences Division IRB, University of Texas MD Anderson Cancer Center IRB, Western IRB, Quorum Review IRB, US Oncology, Inc. IRB, CEIm - Comité de Ética de la Investigación con Medicamentos, Regional Komite for Medisinsk og Helsefagli Forskningsetikk, and REC - Regional Committees for Medical and Health Research Ethics. All participants gave informed consent before taking part in this study.ConsentNo identifying information is contained in this abstract so no permission from participants is considered necessary.

Pembrolizumab (pembro) for the treatment of patients with Bacillus Calmette-Guérin (BCG) unresponsive, high-risk (HR) non–muscle-invasive bladder cancer (NMIBC): Over two years follow-up of KEYNOTE-057.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5041-5041 ◽  
Author(s):  
Arjun Vasant Balar ◽  
Ashish M. Kamat ◽  
Girish S. Kulkarni ◽  
Edward M. Uchio ◽  
Joost L. Boormans ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Complete Response ◽  
Disease Recurrence ◽  
Intravesical Therapy ◽  
Efficacy Analysis ◽  
Bcg Therapy ◽  
Duration Of Response ◽  
Grade 3 ◽  
Muscle Invasive

5041 Background: Pembro was recently approved for the treatment of HR NMIBC based on results from the phase 2 KEYNOTE-057 (NCT02625961) study. Herein we present safety, efficacy, and posttreatment outcomes with > 2 y follow-up from KEYNOTE-057 cohort A. Methods: Patients with histologically confirmed HR BCG-unresponsive carcinoma in situ (CIS) with or without papillary tumors who received adequate BCG therapy and were ineligible for or opted out of radical cystectomy (RC) received pembro 200 mg Q3W for up to 2 y or until disease recurrence, progression, or unacceptable toxicity. The primary end point was complete response rate (CRR). Key secondary end points were duration of response (DOR) and safety. Results: Overall, 102 patients were initially enrolled, and 96 were included in the efficacy analysis. Median time from enrollment to data cut off was 28.4 months (range, 18.2-40.5). CRR was 40.6% (95% CI, 30.7-51.1), and median DOR was 16.2 months (range, 0+ to 30.4+). Among 39 patients with CR, 18 (46.2%) had a DOR ≥12 months. No patient’s disease progressed to muscle-invasive or metastatic bladder cancer while on study treatment. Median PFS and OS were not reached. At 12 months, PFS was 82.7% and OS was 97.9%. A total of 36 patients (37.5%) underwent RC after discontinuation from study treatment, which included 9 of 22 patients (40.9%) who had recurrence after initial CR and 27 of 57 (47.4%) nonresponders. Of the 36 who underwent RC, 33 (91.6%) had no pathological upstaging to MIBC and 3 (8.3%) had at least pT2 disease at time of RC. For subsequent treatments other than RC, 27 of 96 (28.1%) patients received additional intravesical therapy (eg, BCG, gemcitabine, or mitomycin), 21 of 96 (21.9%) underwent local procedures (eg, TURBT), and 3 of 96 (3.1%) received systemic therapy (eg, pembro). In 102 patients treated with pembro, treatment-related AEs (TRAEs) occurred in 67 (65.7%) patients; most frequently reported TRAEs were fatigue, pruritus, and diarrhea (10.8% each). Grade 3/4 TRAEs occurred in 13 patients (12.7%), and 21 patients (20.6%) experienced immune-mediated AEs. There were no grade 5 TRAEs. Conclusions: After > 2 y of follow-up, durable and clinically meaningful activity of pembro was observed in patients who had HR BCG-unresponsive CIS with or without papillary tumors and who were ineligible for or opted out of RC. Pembro did not seem to limit the opportunity for subsequent therapies, including RC. The safety profile was consistent with what is reported in the literature. Clinical trial information: NCT02625961 .

Updated outcomes with axicabtagene ciloleucel (axi-cel) retreatment (reTx) in patients (pts) with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7548-7548
Author(s):  
Julio C. Chavez ◽  
Caron A. Jacobson ◽  
Alison Sehgal ◽  
Sattva Swarup Neelapu ◽  
David G. Maloney ◽  
...  
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Complete Response ◽  
Tumor Burden ◽  
Primary Analysis ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T ◽  
Grade 3

7548 Background: ZUMA-5 is a Phase 2 study of axi-cel anti-CD19 CAR T-cell therapy in pts with R/R iNHL (follicular lymphoma [FL]; marginal zone lymphoma [MZL]). In the primary analysis, 11 pts (9 FL; 2 MZL) were retreated with axi-cel, achieving an overall response rate (ORR) of 100% (91% complete response [CR] rate) at a median follow-up of 2.3 mo post-reTx, with no Grade ≥3 cytokine release syndrome (CRS) or neurologic events (NEs; Chavez et al. ASH 2020. #2036). Here, we report updated clinical and translational outcomes with longer follow-up in pts retreated with axi-cel in ZUMA-5. Methods: Eligible pts with FL or MZL had R/R disease after ≥2 lines of therapy. Pts were considered for reTx if they progressed after a response at mo 3, had no evidence of CD19-negative relapse in biopsy, had no axi-cel neutralizing antibodies, and had no Grade 4 CRS or NEs with 1st Tx. Retreatment was per investigator discretion. At both Txs, pts received axi-cel (2×106 CAR T cells/kg) after conditioning chemotherapy. Results: As of 9/14/2020, 13 pts with iNHL (11 FL; 2 MZL) received axi-cel reTx, with 2 pts retreated after the primary analysis. Before their 1st Tx, pts had median 4 prior lines of therapy; 85% had stage 3–4 disease; 82% had FLIPI of ≥3; 46% were POD24; 77% had refractory disease. Among the 13 retreated pts, 85% had a CR to 1st Tx. Median 1st duration of response (DOR) was 8.2 mo. Detectable CD19 was confirmed in all evaluable biopsies from retreated pts at relapse, and median time from 1st Tx to reTx was 10.6 mo. Following reTx, the ORR was 100% (77% CR rate). After a median follow-up of 11.4 mo, the median DOR had not yet been reached; 46% of retreated pts had ongoing responses at data cutoff. At 1st Tx, CRS occurred in 9 pts (5 Grade 1, 4 Grade 2); NEs occurred in 5 (3 Grade 1, 1 Grade 2, 1 Grade 3). At reTx, CRS occurred in 8 pts (6 Grade 1, 2 Grade 2); NEs occurred in 4 (3 Grade 1, 1 Grade 2). Median peak levels of biomarkers typically associated with severe CRS and NEs were similar at reTx and 1st Tx (IL-6, 7.7 vs 5.7 pg/mL; IL-2, 1.8 vs 0.9 pg/mL; IFN-γ, 62.9 vs 64.2 pg/mL). In the 11 retreated pts with FL, tumor burden (median sum of product diameters [SPD]) was lower before reTx vs 1st Tx (1416 vs 4770 mm2). Engraftment index (CAR T-cell expansion relative to SPD) is an indirect proxy for effector:target ratio and a key covariate of response to axi-cel (Locke et al. Blood Adv. 2020). Though median peak CAR T-cell levels appeared lower at reTx vs 1st Tx (5.2 vs 14.3 CAR+ cells/µL blood), engraftment index was similar (0.003 vs 0.005 cells/µL×mm2). Conclusions: Axi-cel reTx achieved deep and durable responses, with an acceptable safety profile. Tumor CD19 positivity was maintained at relapse, and engraftment index was similar at both Txs, comparing favorably to previous reports in aggressive lymphomas (Locke et al. ASCO 2020. #8012). These data suggest axi-cel reTx is a promising option for pts with R/R iNHL. Clinical trial information: NCT03105336.

Efficacy and safety of nivolumab (NIVO) plus ipilimumab (IPI) in patients with melanoma (MEL) metastatic to the brain: Results of the phase II study CheckMate 204.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9507-9507 ◽  
Author(s):  
Hussein Abdul-Hassan Tawbi ◽  
Peter A. J. Forsyth ◽  
Alain Patrick Algazi ◽  
Omid Hamid ◽  
F. Stephen Hodi ◽  
...  
Keyword(s):  
Objective Response ◽  
Complete Response ◽  
Median Number ◽  
Disease Assessment ◽  
Response Data ◽  
Grade 3 ◽  
Favorable Safety ◽  
The Brain ◽  
Clinical Trial Information

9507 Background: Brain metastases (BMts) are a major cause of morbidity/death in MEL. We report the first efficacy data in MEL patients (pts) with BMts who received NIVO+IPI in study CheckMate 204. Methods: In this multicenter US trial (NCT02320058), MEL pts with ≥1 measurable BMt 0.5-3.0 cm and no neurologic symptoms or steroid Rx received NIVO 1 mg/kg + IPI 3 mg/kg Q3W x 4, then NIVO 3 mg/kg Q2W until progression or toxicity. Pts with severe adverse events (AEs) during NIVO+IPI could receive NIVO when toxicity resolved; stereotactic radiotherapy (SRT) was allowed for brain oligo-progression if an assessable BMt remained. The primary endpoint was intracranial (IC) clinical benefit rate (complete response [CR] + partial response [PR] + stable disease [SD] > 6 months). The planned 90-pt accrual is complete; we report efficacy and updated safety for 75 pts with disease assessment before the Nov 2016 database lock. Results: Median age was 59 yrs (range 22–79). Median number of induction doses was 3; 26 pts (35%) received 4 NIVO+IPI doses and 38 pts (51%) began NIVO maintenance. Response data are reported at a median follow-up of 6.3 months (Table). The IC objective response rate (ORR) was 56% (95% CI: 44–68); 19% of pts had a complete response. IC and extracranial responses were largely concordant. Rx-related grade 3/4 AEs occurred in 48% of pts, 8% neurologic, including headache and syncope. Only 3 pts (4%) stopped Rx for Rx-related neurologic AEs. One pt died of immune-related myocarditis. Conclusions: In CheckMate 204, prospectively designed to investigate NIVO+IPI in MEL pts with BMts, NIVO+IPI had high IC antitumor activity with objective responses in 56% of pts, CR in 19%, and no unexpected neurologic safety signals. The favorable safety and high anti-melanoma activity of NIVO+IPI may represent a new Rx paradigm for pts with asymptomatic MEL BMts and could change practice to avoid or delay whole brain RT or SRT. Clinical trial information: NCT02320058. [Table: see text]

scholarly journals 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150)

2021 ◽  
Vol 11 (10) ◽  
Author(s):  
Andrew H. Wei ◽  
Panayiotis Panayiotidis ◽  
Pau Montesinos ◽  
Kamel Laribi ◽  
Vladimir Ivanov ◽  
...  
Keyword(s):  
Complete Response ◽  
Intensive Chemotherapy ◽  
Primary Analysis ◽  
Free Survival ◽  
Risk Of Death ◽  
Transfusion Independence ◽  
Frontline Treatment ◽  
Grade 3 ◽  
Low Dose Cytarabine

AbstractVIALE-C compared the safety and efficacy of venetoclax or placebo plus low-dose cytarabine (+LDAC) in patients with untreated AML ineligible for intensive chemotherapy. Overall, 211 patients were enrolled (n = 143, venetoclax; n = 68, placebo). At the primary analysis, the study did not meet its primary endpoint of a statistically significant improvement in overall survival (OS), however, ~60% of patients had been on study for ≤6-months. Here, we present an additional 6-months of follow-up of VIALE-C (median follow-up 17.5 months; range 0.1–23.5). Median OS was (venetoclax +LDAC vs. placebo +LDAC) 8.4 vs. 4.1 months (HR = 0.70, 95% CI 0.50,0.99; P = 0.040); a 30% reduction in the risk of death with venetoclax. Complete response (CR)/CR with incomplete hematologic recovery (CRi) rates were 48.3% vs. 13.2%. Transfusion independence rates (RBC) were 43% vs.19% and median event-free survival was 4.9 vs. 2.1 months (HR = 0.61; 95% CI 0.44,0.84; P = 0.002). These results represent improved efficacy over the primary analysis. Incidence of grade ≥3 adverse events were similar between study arms and overall safety profiles were comparable to the primary analysis. These data support venetoclax +LDAC as a frontline treatment option for patients with AML ineligible for intensive chemotherapy.This trial was registered at www.clinicaltrials.gov as #NCT03069352.

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: Final overall survival (OS) results from a randomized, multicenter, open-label, phase 2 study (DESTINY-Gastric01).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4048-4048
Author(s):  
Kensei Yamaguchi ◽  
Yung-Jue Bang ◽  
Satoru Iwasa ◽  
Naotoshi Sugimoto ◽  
Min-Hee Ryu ◽  
...  
Keyword(s):  
Median Survival ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Phase 2 ◽  
Standard Chemotherapy ◽  
Primary Analysis ◽  
Her2 Positive ◽  
Open Label ◽  
Grade 3

4048 Background: T-DXd is an antibody–drug conjugate comprising an anti-HER2 antibody, a cleavable tetrapeptide-based linker, and a topoisomerase I inhibitor. DESTINY-Gastric01 (DS8201-A-J202; ClinicalTrials.gov, NCT03329690) is an open-label, multicenter, randomized, phase 2 trial of T-DXd in patients with HER2-positive advanced gastric cancer (GC) or GEJ adenocarcinoma. In the primary analysis (101 OS events; median survival follow-up, 12.3 mo), T-DXd showed statistically significant benefit vs standard chemotherapy in objective response rate (ORR) and OS (Shitara K, et al. N Engl J Med. 2020;382:2419-2430); here, we present the final OS analysis as well as updated efficacy and safety. Methods: Patients (pts) with locally advanced or metastatic, centrally confirmed HER2-positive (IHC3+ or IHC2+/ISH+ on archival tissue) GC or GEJ cancer that had progressed after ≥2 previous lines of therapy including trastuzumab were randomly assigned 2:1 (T-DXd 6.4 mg/kg Q3W or physician’s choice [PC] irinotecan [I] or paclitaxel [P]). Pts were stratified by country, ECOG performance status (0, 1), and HER2 status. Primary end point was ORR by independent central review. Key secondary end points were OS, duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), confirmed ORR, and safety. Final OS analysis was performed at 133 OS events. Results: 187 pts received T-DXd (n = 125) or PC (n = 62 [55 I; 7 P]); 79.7% of pts were Japanese and 20.3% were Korean. Pts had a median of 2 prior lines of therapy, and 44.4% had ≥3. At data cutoff (June 3, 2020), 8% of T-DXd and 0% of PC pts remained on treatment (median survival follow-up, 18.5 mo). OS was improved with T-DXd vs PC (median OS, 12.5 vs 8.9 mo; hazard ratio [HR], 0.60 [95% CI, 0.42-0.86]); 12-month OS, 52.2% vs 29.7%. ORR was 51.3% (61/119; 11 CR; 50 PR) with T-DXd vs 14.3% (8/56; all PR) with PC ( P < 0.0001); confirmed ORR, 42.0% (50/119; 10 CR; 40 PR) vs 12.5% (7/56; all PR) ( P = 0.0001); DCR, 86.6% vs 62.5% ( P = 0.0003); confirmed median DOR, 12.5 vs 3.9 mo; median PFS, 5.6 vs 3.5 mo (HR, 0.47 [95% CI, 0.31-0.71]; P = 0.0003). Grade ≥3 AEs occurred in 85.6% of T-DXd pts vs 56.5% with PC; the most common were neutrophil count decreased (49.6%, 22.6%), anemia (38.4%, 22.6%), and white blood cell count decreased (20.8%, 11.3%). 16 pts (12.8%) had T-DXd–related interstitial lung disease (ILD; 13 grade 1/2, 2 grade 3, 1 grade 4, no grade 5) vs 0 with PC. As reported in the primary analysis, there was 1 T-DXd–related death from pneumonia (non-ILD). Conclusions: With additional follow-up after the primary analysis, T-DXd continued to demonstrate OS benefit and clinically relevant improvement in ORR compared with standard chemotherapy, and a manageable safety profile, in HER2-positive advanced GC or GEJ adenocarcinoma. Clinical trial information: NCT03329690.

Daratumumab (DARA) in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in patients (pts) with newly diagnosed multiple myeloma (MMY1001): An open-label, phase 1b study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8000-8000 ◽  
Author(s):  
Andrzej J. Jakubowiak ◽  
Ajai Chari ◽  
Sagar Lonial ◽  
Brendan M. Weiss ◽  
Raymond L. Comenzo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Safety Profile ◽  
Standard Of Care ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Open Label ◽  
Frontline Treatment ◽  
Grade 3

8000 Background: DARA in combination with established standard of care regimens prolongs PFS, deepens responses, and demonstrates a favorable safety profile in relapsed or refractory multiple myeloma (MM). The tolerability and efficacy of DARA-KRd in newly diagnosed MM pts was examined. Methods: Newly diagnosed pts regardless of transplantation eligibility were enrolled. Pts received DARA 16 mg/kg QW for Cycles 1-2, Q2W for Cycles 3-6, and Q4W thereafter. All pts received the 1st dose of DARA split over 2 days. Carfilzomib (K) was administered on Days 1, 8 and 15 of each 28-day cycle (20 mg/m2 on C1D1, 36 or 70 mg/m2 subsequently based on tolerability of first dose) for ≤13 cycles or elective discontinuation for ASCT. Lenalidomide 25 mg was given on Days 1-21 and dexamethasone 20-40 mg per week. The primary endpoint was tolerability. Results: Twenty-two pts (median [range] age, 60 [34-74] y) were enrolled and received a median of 8 (1-10) treatment cycles. Nineteen pts escalated K dose to 70 mg/m2 by C1D15. Median (range) duration of follow-up was 7.4 (4.0-9.3) months. Six (27%) pts discontinued treatment (1 AE [pulmonary embolism]; 1 PD; 4 other [ASCT]). Serious AEs occurred in 46% of pts, and 14% were possibly related to DARA; 18 (82%) experienced a grade 3/4 TEAE. The most common grade 3/4 TEAEs (>10%) were lymphopenia (50%) and neutropenia (23%); 1 (5%) cardiac grade 3 TEAE was observed (congestive heart failure) which resolved; pt quickly resumed study treatment with reduced K dose. No grade 5 TEAE was reported. All DARA-associated infusion reactions (27% of pts) were grade ≤2. Treatment with DARA-KRd yielded an ORR (≥partial response) of 100% (5% complete response, 86% ≥very good partial response) in 21 response-evaluable pts. The 6-month PFS rate was 100%. Conclusions: The addition of DARA to KRd was well tolerated; the overall safety profile was consistent with that previously reported for KRd, with no additional toxicity observed with the addition of DARA. Deep and durable responses were observed. These data support further investigation of DARA-KRd as a frontline treatment regimen. Updated data will be presented based on longer follow up. Clinical trial information: NCT01998971.

Denosumab for the treatment of bisphosphonate-refractory hypercalcemia of malignancy (HCM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20512-e20512
Author(s):  
Mimi I-Nan Hu ◽  
Ilya Glezerman ◽  
Sophie Leboulleux ◽  
Karl L. Insogna ◽  
Rasim A. Gucalp ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Serum Calcium ◽  
Complete Response ◽  
Osteonecrosis Of The Jaw ◽  
Open Label ◽  
Serious Adverse Events ◽  
Duration Of Response ◽  
New Treatment ◽  
Grade 3

e20512 Background: HCM, caused primarily by tumor-induced bone resorption, is treated with intravenous (IV) bisphosphonates (BisP), but patients (pts) can relapse or become refractory. Denosumab binds to RANK ligand (RANKL) to inhibit osteoclast-mediated bone resorption. Methods: In this single-arm, open-label, proof-of-concept study, pts with HCM (corrected serum calcium [CSC] >12.5 mg/dL [CTCAE grade ≥3]) despite IV BisP treatment ≥7 and ≤30 days before screening received subcutaneous denosumab 120 mg on days 1, 8, 15, and 28, then every 4 weeks. The primary endpoint was the proportion of pts with CSC ≤11.5 mg/dL (CTCAE grade ≤1) within 10 days of denosumab initiation. Results: The study enrolled33 pts (64% men; mean age 60 years; 76% with advanced solid tumors, 39% with bone metastases [BM]), with a median (25th, 75th percentile [Q1, Q3]) follow-up of 56 (18, 79) days. Median (Q1, Q3) baseline CSC was 13.7 (13.2, 14.2) mg/dL; 19 pts (58%) had HCM symptoms. Median (Q1, Q3) time from last BisP treatment to first dose was 17 (13, 22) days. At day 10, 21 pts (64%) reached CSC ≤11.5 mg/dL, including 54% of pts with BM and 70% without BM. Over the course of the study, 23 pts (70%) reached CSC ≤11.5 mg/dL, by a median (95% confidence interval [CI]) of 9 (5–19) days. A complete response (CSC ≤10.8 mg/dL, as defined by previous studies) occurred in 12 pts (36%) at day 10, and in 21 pts (64%) during the study, by a median (95% CI) of 23 (11–43) days. Among pts who reached CSC ≤11.5 mg/dL, the median (95% CI) duration of response was 104 (9–not estimable) days. The most frequently reported serious adverse events were worsening of HCM (5 pts, 15%) and dyspnea (3 pts, 9%). Two pts had isolated episodes of CSC levels ≤8.0 mg/dL (CTCAE grade 2); no pts had CSC <7.0 mg/dL (grade 3). No osteonecrosis of the jaw was reported. Conclusions: In this study of pts with HCM despite recent IV BisP treatment, denosumab effectively lowered serum calcium to grade ≤1 in 64% of pts within 10 days, and induced durable responses. These findings are particularly meaningful given that pts entered this study with grade ≥3 HCM within a median 17 days after receiving IV BisP. No unexpected safety findings were identified. Denosumab may offer a new treatment option for HCM in these pts. Clinical trial information: NCT00896454.

Efficacy and safety of the combination of nivolumab (NIVO) plus ipilimumab (IPI) in patients with symptomatic melanoma brain metastases (CheckMate 204).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9501-9501 ◽  
Author(s):  
Hussein Abdul-Hassan Tawbi ◽  
Peter A. J. Forsyth ◽  
F. Stephen Hodi ◽  
Christopher D. Lao ◽  
Stergios J. Moschos ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Objective Response ◽  
Complete Response ◽  
High Rate ◽  
Efficacy And Safety ◽  
Neurologic Symptoms ◽  
Melanoma Brain Metastases ◽  
Grade 3 ◽  
Cutoff Date

9501 Background: We previously reported efficacy and safety of NIVO+IPI in patients (pts) with untreated, asymptomatic, melanoma brain metastases (MBM) from the CheckMate 204 study. Here, we provide the first report of NIVO+IPI in pts with symptomatic MBM, and report updated data in pts with asymptomatic MBM. Methods: In this phase II trial, pts with ≥1 measurable, nonirradiated MBM 0.5–3.0 cm were enrolled into two cohorts: (1) those with no neurologic symptoms or steroid Rx (asymptomatic; cohort A); and (2) those with neurologic symptoms, whether or not they were receiving steroid Rx (symptomatic; cohort B). In both cohorts, pts received NIVO 1 mg/kg + IPI 3 mg/kg Q3W × 4, then NIVO 3 mg/kg Q2W until progression or toxicity. The primary endpoint was intracranial clinical benefit rate (CBR; proportion of pts with complete response [CR] + partial response [PR] + stable disease [SD] ≥6 mo). As of the clinical cutoff date on May 1, 2018, all treated pts (101 in cohort A and 18 in cohort B) had been followed for ~6 mo or longer. Results: In this updated analysis of cohort A (median follow-up of 20.6 mo), the CBR was 58.4% (Table). In cohort B, pts received a median of 1 NIVO+IPI dose and 2 of 18 pts (11%) received all 4 doses. At a median follow-up of 5.2 months in cohort B, intracranial objective response rate was 16.7% and the CBR was 22.2%. Grade 3/4 adverse events occurred in 54.5% of pts in cohort A and in 55.6% of pts in cohort B (6.9% and 16.7% in the nervous system, respectively), with one death related to treatment in cohort A (immune-related myocarditis). Conclusions: In pts with asymptomatic MBM, our updated results show a high rate of durable intracranial responses, further supporting NIVO+IPI as a first-line treatment in this population. Intracranial antitumor activity was observed with NIVO+IPI in pts with symptomatic MBM, but further study is needed to understand the biologic mechanisms of resistance to immunotherapy and to improve treatments in this challenging population. Clinical trial information: NCT02320058. [Table: see text]

Long-term analyses from L-MIND, a phase II study of tafasitamab (MOR208) combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7513-7513
Author(s):  
Johannes Düll ◽  
Kami J. Maddocks ◽  
Eva Gonzalez-Barca ◽  
Wojciech Jurczak ◽  
Anna Marina Liberati ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Open Label ◽  
Efficacy Analysis

7513 Background: L-MIND (NCT02399085) is an ongoing, open-label, Phase II study of tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, plus LEN in ASCT-ineligible patients (pts) with R/R DLBCL. Primary analyses and 2-year efficacy results were previously presented; we report an updated efficacy analysis with ≥35 months follow up (cut-off: October 30, 2020). Methods: Pts were aged ≥18 years with ASCT-ineligible R/R DLBCL, had 1–3 prior systemic therapies (Tx), including ≥1 CD20-targeting regimen, with an ECOG status of 0–2. Pts received 28-day cycles (C) of tafasitamab (12 mg/kg IV), once weekly during C1–3, with a loading dose on Day 4 of C1, then every 2 weeks (Q2W) during C4–12. LEN (25 mg PO) was administered on Days 1–21 of C1–12. After C12, progression-free pts received tafasitamab Q2W until disease progression. The primary endpoint was objective response rate (ORR), assessed by IRC. Secondary endpoints included duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Results: Eighty of 81 enrolled pts received tafasitamab + LEN and were included in the full analysis set (1 prior Tx, n=40; 2+ prior Tx, n=40). At data cut-off, the overall ORR was 57.5% (n=46/80), including complete response (CR) in 40% of pts (n=32/80) and partial response (PR) in 17.5% of pts (n=14/80) (Table). Kaplan-Meier estimates: median DoR=43.9 months (95% CI: 26.1–not reached [NR]), and NR in pts who achieved a CR (95% CI: 43.9–NR); median PFS=11.6 months (95% CI: 6.3–45.7), with median follow-up 33.9 months; median OS=33.5 months (95% CI: 18.3–NR), with median follow-up 42.7 months. There were no unexpected toxicities or new safety signals. Conclusions: Combination Tx with tafasitamab + LEN followed by tafasitamab monotherapy provided durable responses in pts with R/R DLBCL not eligible for ASCT, with a manageable safety profile. These long-term data indicate the potential of tafasitamab + LEN followed by extended tafasitamab monotherapy in achieving prolonged remission and survival benefit in this patient population, especially at first relapse. Clinical trial information: NCT02399085. [Table: see text]

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