scholarly journals 1037O MASTERKEY-265: A phase III, randomized, placebo (Pbo)-controlled study of talimogene laherparepvec (T) plus pembrolizumab (P) for unresectable stage IIIB–IVM1c melanoma (MEL)

2021 ◽  
Vol 32 ◽  
pp. S868-S869
Author(s):  
A. Ribas ◽  
J. Chesney ◽  
G.V. Long ◽  
J.M. Kirkwood ◽  
R. Dummer ◽  
...  
Keyword(s):  
Stage Iiib ◽  
Phase Iii ◽  
Controlled Study ◽  
Talimogene Laherparepvec ◽  
Unresectable Stage

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.

A phase III study of Æ-941 with induction chemotherapy (IC) and concomitant chemoradiotherapy (CRT) for stage III non- small cell lung cancer (NSCLC) (NCI T99–0046, RTOG 02–70, MDA 99–303)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7527-7527 ◽  
Author(s):  
C. Lu ◽  
J. J. Lee ◽  
R. Komaki ◽  
R. S. Herbst ◽  
W. K. Evans ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Performance Status ◽  
Stage Iiib ◽  
Phase Iii ◽  
Stage Iii ◽  
Type I ◽  
Eligibility Criteria ◽  
Unresectable Stage ◽  
Significant Difference ◽  
Stage Iii Nsclc

7527 Background: Æ-941 is a shark cartilage extract with antiangiogenic properties. We conducted a placebo-controlled trial testing Æ-941, with IC and CRT, in unresectable stage III NSCLC. Methods: Eligibility criteria included performance status (PS) < 2, weight loss < 10%. Subjects received one of two treatment regimens depending on site of enrollment: carboplatin (C) (AUC 6) and paclitaxel (P) (200 mg/m2) × 2 cycles followed by CRT (60 Gy/30 fractions) with weekly C (AUC 2) and P (45 mg/m2) × 6 doses or cisplatin (CDDP) (75 mg/m2, d1) and vinorelbine (V) (30 mg/m2, d1 and 8) × 2 cycles followed by CRT (60 Gy/30 fractions) with CDDP (75 mg/m2, day 1) and V (15 mg/m2, d1 and 8) × 2 cycles. Subjects were randomized to receive Æ-941 (Arm A) or placebo (Arm B), 120 mL orally twice daily, at the start of IC and continuing after CRT as maintenance therapy. Randomization was stratified for stage, gender, and type of chemotherapy. The primary endpoint was overall survival (OS), with a planned sample size of 756 subjects providing 80% power to detect a 25% difference in OS, assuming a control arm median survival time (MST) of 13 months, type I error 0.05. Results: Between 6/00 and 2/06, 384 subjects were enrolled onto the trial and randomized. In 2/06 the trial was closed to new patient entry due to insufficient accrual. This final analysis is based on 379 randomized and eligible subjects (188 arm A, 191 arm B). Subject characteristics: 60% male, median age 63 years (range 37–84), 56% stage IIIB, 58% C-based chemotherapy, median follow-up 3.7 years. There was no significant difference in OS between arms A and B, with MSTs of 14.4 (95% CI 12.6–17.9) and 15.6 (95% CI 13.8–18.1) months, respectively (log-rank p=0.73). OS by pre-specified stratification factors: stage IIIB vs IIIA (MST 13.9 vs. 17.4 months, p=0.25), C vs. CDDP chemotherapy (MST 14.4 vs. 16.7 months, p=0.13), and male vs. female (MST 15.7 vs. 15.1 months, p=0.74). The study drug was well tolerated. Fewer subjects in arm A experienced grade 3 or higher adverse events (66% vs. 77%, p=0.018). Conclusions: The addition of Æ−941 to IC and CRT does not improve OS in patients with unresectable stage III NSCLC. No significant financial relationships to disclose.

A multi-centre, open-label study to assess the safety of Stimuvax (BLP25 liposome vaccine or L-BLP25) in non-small cell lung cancer (NSCLC) patients (pts) with unresectable stage III disease

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3075-3075
Author(s):  
D. Soulieres ◽  
C. Smith ◽  
P. M. Ellis ◽  
N. Murray ◽  
K. Jasas ◽  
...  
Keyword(s):  
Adverse Event ◽  
Stable Disease ◽  
Objective Response ◽  
Stage Iiib ◽  
Phase Iii ◽  
Stage Iii ◽  
Stage Iiia ◽  
Monophosphoryl Lipid A ◽  
Unresectable Stage ◽  
System L

3075 Background: L-BLP25 is an innovative cancer vaccine that incorporates a synthetic MUC1 lipopeptide in a liposomal delivery system. L-BLP25 is expected to elicit an immune response to cancer cells that express MUC1. Previous clinical studies have demonstrated that L-BLP25 has the potential to extend survival of pts with stage IIIB locoregional NSCLC (Butts C et al., JCO 2005; 23:6674–6681). The present ph I-II study was designed to assess the safety of the current formulation of L-BLP25 using a monophosphoryl lipid A in pts with unresectable stage IIIA and stage IIIB NSCLC. Methods: Pts with stable disease or an objective response to upfront radical therapy with chemoradiation for unresectable stage III NSCLC, plus ECOG 0–1 were eligible. All pts were vaccinated according to a previously described schedule (1). Maintenance immunizations were administered every 6-wks until disease progression. Primary and secondary endpoints were safety and survival respectively. Results: Twenty-two pts were recruited at 7 sites in Canada. 16 pts were evaluated for this interim safety analysis (8 stage IIIA, 8 stage IIIB, median age; 57, ECOG 0 56%, concurrent chemotherapy; 93.8%). Thirteen pts had a partial response and 3 had stable disease following chemoradiation. Thirteen pts experienced an adverse event (AE) during the first 4 vaccinations of which 7 pts had a L-BLP25 related adverse event. Grade 1/2 AEs related to L-BLP25 ≥10% included fatigue, dyspnea, insomnia, anorexia, headache, diarrhea, paresthesia, abdominal pain, influenza-like illness, urinary tract infection and peripheral neuropathy. No pts discontinued L-BLP25 due to an AE and no grade 3/4 AEs related to L-BLP25 were reported. Six pts (37.5%) had an injection site reaction. As of September 2006, 10 pts were still on study treatment. Conclusions: This formulation of L-BLP25 was well tolerated and the side effect profile was similar to that seen in previous studies (1). A controlled global multi-center phase III trial is underway to further evaluate L-BLP25 in this patient population. No significant financial relationships to disclose.

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

OPTiM: A randomized phase III trial to evaluate the efficacy and safety of talimogene laherparepvec (T-VEC) compared with subcutaneously (sc) administered GM-CSF for the treatment (tx) of unresectable stage IIIb, IIIc, and IV melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS8604-TPS8604
Author(s):  
Howard Kaufman ◽  
Volker Jean Wagner ◽  
Howard Goldsweig ◽  
Bin Yao ◽  
Robert Coffin
Keyword(s):  
Stage Iiib ◽  
High Rate ◽  
Phase Iii ◽  
Fisher Exact Test ◽  
Efficacy And Safety ◽  
Eligibility Criteria ◽  
Durable Response ◽  
Exact Test ◽  
Gm Csf ◽  
Unresectable Stage

TPS8604 Background: T-VEC (formerly OncoVEXGM-CSF) is an oncolytic HSV1 that selectively replicates in tumors. The proposed MOA includes lytic destruction of injected tumors and induction of a systemic anti-tumor immune response enhanced by local GM-CSF expression. Intratumoral T-VEC tx in a 50-patient (pt) ph II study in advanced melanoma (Stage IIIc-IVM1c) was well tolerated and achieved a high rate and duration of response, including 20% CR (Senzer et al., JCO 2009; 27: 5763-71). As immune effects may be delayed, progressive disease (PD) often occurred before response. Based on the ph II data, a randomized ph III trial of T-VEC in unresectable melanoma (the OPTiM study; clinical trials registry NCT00769704) was designed taking into account the response patterns seen with T-VEC and other immunotherapeutic agents. T-VEC is the first "armed" oncolytic agent to enter pivotal testing worldwide. Methods: OPTiM compares the efficacy and safety of intratumoral T-VEC to sc GM-CSF in 430 pts with treated or untreated unresectable Stage IIIb-IVM1c melanoma stratified by typical prognostic factors. Pts are randomized 2:1 to T-VEC (priming dose of up to 4 x 106 pfu intratumorally then 3 wks later by up to 4 x 108 pfu Q2W) or GM-CSF 125 µg/m2 qd sc x 14 days every 28 days. Key eligibility criteria are ≥ 18 yrs old, ECOG 0-1, and at least 1 injectable cutaneous, sc, or nodal tumor. The primary endpoint is durable response rate (DRR: CR or PR continuously maintained for ≥ 6 mo initiating within 12 mo of starting tx; secondary endpoints include OS. Responses are subject to independent review. Pts are treated until wk 24, even with PD. Thereafter pts are treated until clinically significant PD, CR, or for 1 yr. The study has 90% power to show a 10% difference in DRR with 2-sided Fisher Exact Test (α = 5%). Enrollment closed in July 2011 with 439 pts randomized in the US, UK, S Africa, and Canada. Interim analysis in Dec 2010 on 75 pts on study > 9 mo concluded that the study should continue. Results are expected during 2012. Conclusions: T-VEC provides a novel potential tx for melanoma. This pivotal ph III study is expected to report during 2012.

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