429 Long-term analysis of MASTERKEY-265 phase 1b trial of talimogene laherparepvec (T-VEC) plus pembrolizumab in patients with unresectable stage IIIB-IVM1c melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A454-A454
Author(s):  
Georgina Long ◽  
Reinhard Dummer ◽  
Douglas Johnson ◽  
Olivier Michielin ◽  
Salvador Martin-Algarra ◽  
...  
Keyword(s):  
Pigment Cell ◽  
Objective Response ◽  
Stage Iiib ◽  
List Type ◽  
Talimogene Laherparepvec ◽  
Unresectable Stage ◽  
Long Term Follow Up ◽  
Phase 1B

BackgroundPrevious findings from the MASTERKEY-265 phase 1b study showed that the combination of T-VEC and pembrolizumab was well tolerated and produced a high complete response (CR) rate of 43% in patients with advanced melanoma.1 The 3-year progression-free survival (PFS) and overall survival (OS) rates at that time were 53.6% and 71%, respectively. Here, we report the results of the long-term follow-up efficacy analyses.MethodsThe MASTERKEY-265 phase 1b trial (NCT02263508) was an open-label, single-arm study that enrolled patients who had unresectable, stage IIIB-IVM1c melanoma with injectable, measurable lesions and no prior systemic treatment. T-VEC was administered intralesionally at the approved dosing starting day 1 of week 1. Pembrolizumab (200 mg) was administered intravenously Q2W beginning on day 1 of week 6. The maximum treatment period was 2 years. The primary endpoint was dose-limiting toxicities; key secondary endpoints included objective response rate and PFS per modified irRC, OS, and safety.ResultsAs of the data cutoff (Mar 2, 2020), all 21 patients enrolled were off treatment; 6 died and 15 are in long-term follow-up. The median follow-up time was 58.6 months (range: 1.4–61.6). The CR rate remained 43% (9/21 patients). Twelve of the 13 responders (92.3%) are still in response, including all 9 patients with a CR. Median duration of response was not reached (range: 2.8+–54.3+ months). Median PFS and OS were not reached at the data cutoff. KM estimates of 4-year PFS and OS rates were 55.9% and 71.4%, respectively, which have held stable since the 3-year analysis. Patients who achieved a CR or partial response had better OS (p=0.0056) compared to those who did not respond. Median OS for non-responders was 24.4 months and was not reached for responders. No additional safety signals were detected.ConclusionsAt almost 5 years of follow-up, median PFS and OS were not reached for patients treated with the combination of T-VEC and pembrolizumab in this phase 1b study of unresectable metastatic melanoma. 92% of responders remained in response with improved OS observed in responders compared with non-responders. The corresponding randomized phase 3 trial has completed enrollment and is currently ongoing.Trial RegistrationNCT02263508Ethics ApprovalThe study was approved by the Ethics Board of each institution involved in this study and can be produced upon request.ReferenceLong G, Dummer R, Andtbacka R, et al. Follow-up analysis of MASTERKEY-265 Phase 1b (ph1b) trial of talimogene laherparepvec (T-VEC) in combination (combo) with pembrolizumab (pembro) in patients (pts) with unresectable stage IIIB–IVM1c melanoma (MEL). Pigment Cell Melanoma Res 2019;32:133–134.

Two dosing regimens of nivolumab (NIVO) plus ipilimumab (IPI) for advanced (adv) melanoma: Three-year results of CheckMate 511.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9516-9516
Author(s):  
Celeste Lebbe ◽  
Nicolas Meyer ◽  
Laurent Mortier ◽  
Ivan Marquez-Rodas ◽  
Caroline Robert ◽  
...  
Keyword(s):  
Safety Profile ◽  
Objective Response ◽  
Progression Free Survival ◽  
Unresectable Stage ◽  
Long Term Follow Up ◽  
Dosing Regimens ◽  
Secondary Endpoints ◽  
To Receive

9516 Background: NIVO 1 mg/kg plus IPI 3 mg/kg (NIVO1 + IPI3) is approved for treatment (tx) of unresectable/adv melanoma, with demonstrated durable clinical benefit on long-term follow-up. Analysis of the phase 3b/4 CheckMate 511 study (NCT02714218) at 1 y showed that NIVO 3 mg/kg plus IPI 1 mg/kg (NIVO3 + IPI1) improves the safety profile of the combination; efficacy with the 2 regimens was similar in descriptive analyses. Here we present 3-y safety/efficacy results. Methods: Patients (pts) ≥ 18 y of age with previously untreated unresectable stage III/IV melanoma were randomized 1:1 to receive NIVO3 + IPI1 Q3W × 4 (N = 180) or NIVO1 + IPI3 Q3W × 4 (N = 178), both followed by NIVO 480 mg Q4W until progression/unacceptable toxicity. The primary endpoint was the incidence of grade (gr) 3–5 tx-related adverse events (TRAEs); secondary endpoints (descriptive analyses) included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The study was not powered to formally demonstrate noninferiority for efficacy endpoints. Results: At a median follow-up of 44.4 and 43.9 mo in the NIVO3 + IPI1 and NIVO1 + IPI3 groups, respectively, TRAEs led to tx discontinuation in 26% and 39% of pts; 57% and 42% of pts had received maintenance therapy. Gr 3–5 TRAE incidence remained significantly lower with NIVO3 + IPI1 than NIVO1 + IPI3 (33.9% vs 48.3%; odds ratio 0.55 [95% CI 0.36–0.84]). The most frequent TRAEs (any gr) were diarrhea (27%), fatigue (26%), and pruritus (26%) with NIVO3 + IPI1 and diarrhea (31%), pruritus (29%), and rash (27%) with NIVO1 + IPI3. In descriptive analyses, efficacy results were similar to those observed at 1 y. OS and tx-free–analysis outcomes were numerically similar in the 2 groups (table). Conclusions: At 3-y follow-up, NIVO3 + IPI1 continued to demonstrate an improved safety profile compared with NIVO1 + IPI3. In descriptive analyses, both groups demonstrated high 3-y OS rates that were numerically similar. This study provides important information regarding the benefit–risk profile of both dosing regimens of NIVO + IPI in pts with adv melanoma. Clinical trial information: NCT02714218. [Table: see text]

Efficacy analysis of MASTERKEY-265 phase 1b study of talimogene laherparepvec (T-VEC) and pembrolizumab (pembro) for unresectable stage IIIB-IV melanoma.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 9568-9568 ◽  
Author(s):  
Georgina V. Long ◽  
Reinhard Dummer ◽  
Antoni Ribas ◽  
Igor Puzanov ◽  
Ari VanderWalde ◽  
...  
Keyword(s):  
Stage Iiib ◽  
Talimogene Laherparepvec ◽  
Efficacy Analysis ◽  
Unresectable Stage ◽  
Phase 1B

Phase 1b study of avelumab in advanced previously treated mesothelioma: long-term follow-up from JAVELIN Solid Tumor.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 8563-8563 ◽  
Author(s):  
Raffit Hassan ◽  
Anish Thomas ◽  
John J. Nemunaitis ◽  
Manish R. Patel ◽  
Jaafar Bennouna ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Long Term Follow Up ◽  
Previously Treated ◽  
Phase 1B

scholarly journals Overall Survival of Patients With Unresectable or Metastatic BRAF V600-Mutant Acral/Cutaneous Melanoma Administered Dabrafenib Plus Trametinib: Long-Term Follow-Up of a Multicenter, Single-Arm Phase IIa Trial

2021 ◽  
Vol 11 ◽  
Author(s):  
Lili Mao ◽  
Ya Ding ◽  
Xue Bai ◽  
Xinan Sheng ◽  
Jie Dai ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cutaneous Melanoma ◽  
Objective Response ◽  
Chinese Patients ◽  
Term Survival ◽  
Long Term Survival ◽  
Acral Melanoma ◽  
Long Term Follow Up

ObjectivesTo examine the long-term survival outcome of dabrafenib in combination with trametinib in Chinese patients with unresectable or metastatic acral/cutaneous melanoma with BRAF-V600 mutation and to explore potential predictors of effectiveness.MethodsThis was a long-term follow-up of Chinese patients with unresectable or metastatic BRAF V600-mutant acral/cutaneous melanoma administered dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) in an open-label, multicenter, single-arm, phase IIa study (NCT02083354). Efficacy endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). The impacts of baseline characteristics on PFS and OS were analyzed.ResultsA total of sixty patients were included. The median age was 48 years, and 24 patients (40.0%) were male. Totally 12 individuals (20.0%) had acral melanoma, and 45 (75.0%) had failed previous systemic therapy. Up to July 2020, the median duration of follow-up was 37.0 (95% confidence interval [CI] 29.1-44.9) months. The updated ORR was 71.7% (95%CI 60.3%-83.1%). The 3-year OS rate was 28.8% (95%CI 19.1-43.6%) in the overall population, and 35.7% (95%CI 15.5–82.4%) in acral melanoma patients. The median DOR was 7.5 months (95%CI 4.5 to 10.5). Baseline normal lactic dehydrogenase (LDH), metastatic organ sites<3 and complete response to combination therapy with dabrafenib plus trametinib were associated with improved PFS and OS.ConclusionDabrafenib combined with trametinib confer long-term survival in Chinese patients with BRAF V600-mutant, unresectable or metastatic acral/cutaneous melanoma.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT02083354, identifier NCT02083354.

scholarly journals Late presentation of acromegaly in medically controlled prolactinoma patients

2016 ◽  
Vol 2016 ◽  
Author(s):  
Ekaterina Manuylova ◽  
Laura M Calvi ◽  
Catherine Hastings ◽  
G Edward Vates ◽  
Mahlon D Johnson ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Dopamine Agonists ◽  
Late Presentation ◽  
List Type ◽  
Biochemical Control ◽  
Current Recommendation ◽  
Long Term Follow Up ◽  
Learning Points

Summary Co-secretion of growth hormone (GH) and prolactin (PRL) from a single pituitary adenoma is common. In fact, up to 25% of patients with acromegaly may have PRL co-secretion. The prevalence of acromegaly among patients with a newly diagnosed prolactinoma is unknown. Given the possibility of mixed GH and PRL co-secretion, the current recommendation is to obtain an insulin-like growth factor-1 (IGF-1) in patients with prolactinoma at the initial diagnosis. Long-term follow-up of IGF-1 is not routinely done. Here, we report two cases of well-controlled prolactinoma on dopamine agonists with the development of acromegaly 10–20 years after the initial diagnoses. In both patients, a mixed PRL/GH-cosecreting adenoma was confirmed on the pathology examination after transsphenoidal surgery (TSS). Therefore, periodic routine measurements of IGF-1 should be considered regardless of the duration and biochemical control of prolactinoma. Learning points: Acromegaly can develop in patients with well-controlled prolactinoma on dopamine agonists. The interval between prolactinoma and acromegaly diagnoses can be several decades. Periodic screening of patients with prolactinoma for growth hormone excess should be considered and can 
lead to an early diagnosis of acromegaly before the development of complications.

Exceptional responders to abexinostat (ABX) plus pazopanib (PAZ) in pretreated renal cell carcinoma (RCC) and other solid tumors: Long-term follow-up of a phase 1b study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3022-3022 ◽  
Author(s):  
Rahul Raj Aggarwal ◽  
Scott Thomas ◽  
Nela Pawlowska ◽  
Jennifer A. Grabowsky ◽  
Susan Calabrese ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Disease Progression ◽  
Clinical Outcomes ◽  
Targeting Therapy ◽  
Study Results ◽  
Duration Of Response ◽  
Long Term Follow Up ◽  
Phase 1B

3022 Background: We previously reported the initial phase 1b study results of PAZ + ABX, a potent pan-HDAC inhibitor, demonstrating acceptable toxicity profile and encouraging anti-tumor activity (Aggarwal et al. JCO 2017). We report the long-term follow up of exceptional responders and additional correlative analyses associated with clinical outcomes. Methods: Key efficacy endpoints included objective response rate and duration of response. Peripheral blood histone acetylation, HDAC expression, and plasma VEGF levels were analyzed and associated with clinical outcomes. Results: 51 pts (RCC subset; N = 22) were enrolled between June 2012 and October 2015. 10 pts (20%) had experienced disease progression on prior PAZ; 59% had received any prior VEGF-targeting therapy. 9 evaluable pts (18%) (N = 6 RCC; 2 thyroid; 1 mesothelioma) achieved partial tumor response (PR), of which 6 had prior progression on VEGF-targeting therapy. 7/10 (70%) of pts with prior disease progression on PAZ monotherapy had reduction in tumor burden on study. The median duration of response was 9.1 months (range 1.2 to 70+), and clinical benefit rate (PR or stable disease > 6 months) was 33%. Five treatment-refractory pts achieved durable PRs lasting for > 2 years duration, and one previously PAZ-refractory patient with RCC remains on treatment with ongoing PR for > 6 years. Higher HDAC2 expression was associated with prolonged progression-free survival (median PFS 5.9 vs. 3.5 months, log-rank p = 0.02). Induction of histone acetylation on ABX lead-in treatment was associated with subsequent time to progression (p = 0.002). On-treatment plasma VEGF levels were inversely correlated with PBMC histone acetylation (p = 0.02). Conclusions: Markedly durable responses with PAZ + ABX are achievable, including in pts with PAZ- and VEGF-refractory RCC and other solid tumor malignancies. Host factors including HDAC expression and acetylation status may identify those most likely to benefit. A randomized phase 3 study is underway of PAZ + ABX as a first- or second-line therapy in pts with locally advanced or metastatic RCC (RENAVIV; NCT03592472). Clinical trial information: NCT01543763.

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