PMID- 36521418
OWN - NLM
STAT- MEDLINE
DCOM- 20221227
LR  - 20230106
IS  - 2059-7029 (Electronic)
IS  - 2059-7029 (Linking)
VI  - 7
IP  - 6
DP  - 2022 Dec
TI  - MOVIE: a phase I, open-label, multicenter study to evaluate the safety and 
      tolerability of metronomic vinorelbine combined with durvalumab plus tremelimumab 
      in patients with advanced solid tumors.
PG  - 100646
LID - S2059-7029(22)00280-0 [pii]
LID - 10.1016/j.esmoop.2022.100646 [doi]
LID - 100646
AB  - BACKGROUND: Anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1 
      (PD-L1) agents have only moderate antitumor activity in some advanced solid 
      tumors (AST), including breast cancer (BC), prostate cancer (PC), cervical cancer 
      (CC), and head and neck cancer (HNC). Combining anti-PD-L1 with anti-cytotoxic 
      T-lymphocyte-associated protein (CTLA) and chemotherapy may significantly improve 
      efficacy. PATIENTS AND METHODS: MOVIE is a multicohort phase I/II study examining 
      the combination of anti-PD-L1 durvalumab (Durv; 1500 mg IV Q4W) plus anti-CTLA 
      tremelimumab (Trem; 75 mg IV Q4W) with metronomic vinorelbine (MVino; 20-40 mg 
      orally daily) in various AST resistant to conventional therapies. The primary 
      objective of the phase I part was to determine the maximum tolerated dose (MTD) 
      and recommended dose for phase II (RP2D). RESULTS: Among the 14 patients enrolled 
      during phase I, including 13 women and 1 man, 9 had BC, 1 PC, 2 CC, and 2 
      miscellaneous cancers with high mutational loads. Median age was 53 years. A 
      total of 12 patients were assessable for the dose-escalation part in which only 
      one dose-limiting toxicity (DLT) was observed [one neutropenia without fever, 
      grade (G) 4]. Two (14.3%), four (28.6%), and four (28.6%) patients had G >/=3 
      adverse events (AEs) related to MVino, Durv, and Trem, respectively. 
      Treatment-related events included mostly clinical AEs with asthenia (eight G2; 
      three G3), colitis (one G2, one G3), diarrhea (one G3), nausea (two G2), dry skin 
      (two G2), maculopapular rash (one G3), and hyperthyroidism (three G2). No toxic 
      death was reported. Preliminary data showed one patient (CC) who presented a 
      complete response and four patients with stable disease (SD). CONCLUSIONS: MTD 
      was not reached and dose level 2 (MVino 40 mg, Durv 1500 mg, Trem 75 mg) was 
      selected as RP2D. The safety profile of the combination was manageable and 
      consistent with previous reports of Trem + Durv or MVino. Phase II is currently 
      ongoing in BC, PC, CC, HNC, and miscellaneous cohorts.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Vicier, C
AU  - Vicier C
AD  - Department of Medical Oncology, Inserm U1068, CNRS UMR7258, Paoli-Calmettes 
      Institute, Aix-Marseille University, Marseille, France.
FAU - Isambert, N
AU  - Isambert N
AD  - Service d'Oncologie medicale, CLCC Georges-Francois Leclerc, Dijon Cedex, France.
FAU - Cropet, C
AU  - Cropet C
AD  - Department of Biostatistics, Direction of Research and Innovation, Centre Leon 
      Berard, Lyon, France.
FAU - Hamimed, M
AU  - Hamimed M
AD  - SMARTc unit, Centre de Recherche en Cancerologie de Marseille (CRCM) UMR INSERM 
      U1068, Aix-Marseille University (AMU), Marseille, France.
FAU - Osanno, L
AU  - Osanno L
AD  - SMARTc unit, Centre de Recherche en Cancerologie de Marseille (CRCM) UMR INSERM 
      U1068, Aix-Marseille University (AMU), Marseille, France.
FAU - Legrand, F
AU  - Legrand F
AD  - UNICANCER, Department of Research & Development, Paris, France.
FAU - de La Motte Rouge, T
AU  - de La Motte Rouge T
AD  - Eugene-Marquis Centre, Avenue de la Bataille Flandres-Dunkerque, Rennes Cedex, 
      France.
FAU - Ciccolini, J
AU  - Ciccolini J
AD  - SMARTc unit, Centre de Recherche en Cancerologie de Marseille (CRCM) UMR INSERM 
      U1068, Aix-Marseille University (AMU), Marseille, France.
FAU - Goncalves, A
AU  - Goncalves A
AD  - Department of Medical Oncology, Inserm U1068, CNRS UMR7258, Paoli-Calmettes 
      Institute, Aix-Marseille University, Marseille, France. Electronic address: 
      goncalvesa@ipc.unicancer.fr.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20221213
PL  - England
TA  - ESMO Open
JT  - ESMO open
JID - 101690685
RN  - 28X28X9OKV (durvalumab)
RN  - QEN1X95CIX (tremelimumab)
RN  - Q6C979R91Y (Vinorelbine)
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Male
MH  - Humans
MH  - Female
MH  - Middle Aged
MH  - Vinorelbine/pharmacology
MH  - Motion Pictures
MH  - *Antineoplastic Agents/adverse effects
MH  - *Head and Neck Neoplasms/chemically induced
MH  - *Uterine Cervical Neoplasms
PMC - PMC9808477
OTO - NOTNLM
OT  - advanced solid tumors (AST)
OT  - durvalumab (Durv)
OT  - immunotherapy
OT  - metronomic vinorelbine (MVino)
OT  - tremelimumab (Trem)
COIS- Disclosure The authors have declared no conflicts of interest.
EDAT- 2022/12/16 06:00
MHDA- 2022/12/28 06:00
PMCR- 2022/12/13
CRDT- 2022/12/15 18:32
PHST- 2022/08/25 00:00 [received]
PHST- 2022/10/09 00:00 [revised]
PHST- 2022/10/26 00:00 [accepted]
PHST- 2022/12/16 06:00 [pubmed]
PHST- 2022/12/28 06:00 [medline]
PHST- 2022/12/15 18:32 [entrez]
PHST- 2022/12/13 00:00 [pmc-release]
AID - S2059-7029(22)00280-0 [pii]
AID - 100646 [pii]
AID - 10.1016/j.esmoop.2022.100646 [doi]
PST - ppublish
SO  - ESMO Open. 2022 Dec;7(6):100646. doi: 10.1016/j.esmoop.2022.100646. Epub 2022 Dec 
      13.