PMID- 34165660
OWN - NLM
STAT- MEDLINE
DCOM- 20210921
LR  - 20220531
IS  - 1437-7772 (Electronic)
IS  - 1341-9625 (Print)
IS  - 1341-9625 (Linking)
VI  - 26
IP  - 10
DP  - 2021 Oct
TI  - A phase I, single-center, open-label study of RM-1929 photoimmunotherapy in 
      Japanese patients with recurrent head and neck squamous cell carcinoma.
PG  - 1812-1821
LID - 10.1007/s10147-021-01960-6 [doi]
AB  - BACKGROUND: To determine the safety, preliminary efficacy, pharmacokinetics, and 
      immunogenicity of a single cycle of RM-1929 photoimmunotherapy, an anti-EGFR 
      antibody cetuximab conjugated with a light-activatable dye (IRDye((R))700DX), in 
      Japanese patients with recurrent head and neck squamous cell carcinoma (rHNSCC). 
      METHODS: Patients received a single fixed dose (640 mg/m(2)) of RM-1929 and a 
      fixed light treatment dose (50 J/cm(2) for superficial illumination; 100 J/cm 
      fiber diffuser length for interstitial illumination). Safety, tumor response 
      (modified RECIST v1.1 by central radiology review), pharmacokinetics, and 
      immunogenicity were evaluated. RESULTS: Three Japanese patients were enrolled who 
      had failed >/= 3 prior lines of therapy including radiation, chemotherapy, 
      cetuximab, and immunotherapy. Target lesions were: submental lesion; right 
      superficial cervical node lesion and oropharynx lesion; and external auditory 
      canal lesion. All patients experienced >/= 1 treatment-emergent adverse event 
      (TEAE), but none were considered dose-limiting. TEAEs were mild to moderate in 
      severity except for one grade 3 application-site pain, which was transient, 
      resolved without sequelae within 24 h, and did not affect study treatment 
      administration. Thirteen of 17 TEAEs reported were possibly or probably related 
      to study treatment. Three patient reports of application-site pain and localized 
      edema were deemed probably related to study treatment. Objective response was 
      observed in two patients (both partial responses). The third patient had disease 
      progression. RM-1929 concentrations and pharmacokinetic parameters were similar 
      in all patients. No patients tested positive for anti-drug antibodies. 
      CONCLUSIONS: RM-1929 photoimmunotherapy showed a manageable safety profile in 
      rHNSCC. Tumor response in these heavily pre-treated patients was clinically 
      meaningful and warrants further investigation. CLINICAL TRIAL REGISTRATION: The 
      trial was registered with the Japanese registry of clinical trials as 
      jRCT2031200133.
CI  - (c) 2021. The Author(s).
FAU - Tahara, Makoto
AU  - Tahara M
AUID- ORCID: 0000-0001-9035-3106
AD  - Department of Head and Neck Medical Oncology, National Cancer Center Hospital 
      East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 
      matahara@east.ncc.go.jp.
FAU - Okano, Susumu
AU  - Okano S
AD  - Department of Head and Neck Medical Oncology, National Cancer Center Hospital 
      East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
FAU - Enokida, Tomohiro
AU  - Enokida T
AD  - Department of Head and Neck Medical Oncology, National Cancer Center Hospital 
      East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
FAU - Ueda, Yuri
AU  - Ueda Y
AD  - Department of Head and Neck Medical Oncology, National Cancer Center Hospital 
      East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
FAU - Fujisawa, Takao
AU  - Fujisawa T
AD  - Department of Head and Neck Medical Oncology, National Cancer Center Hospital 
      East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
FAU - Shinozaki, Takeshi
AU  - Shinozaki T
AD  - Department of Head and Neck Surgery, National Cancer Center Hospital East, 
      Kashiwa, Chiba, Japan.
FAU - Tomioka, Toshifumi
AU  - Tomioka T
AD  - Department of Head and Neck Surgery, National Cancer Center Hospital East, 
      Kashiwa, Chiba, Japan.
FAU - Okano, Wataru
AU  - Okano W
AD  - Department of Head and Neck Surgery, National Cancer Center Hospital East, 
      Kashiwa, Chiba, Japan.
FAU - Biel, Merrill A
AU  - Biel MA
AD  - Clinical Development, Rakuten Medical Inc., 900 Concar Drive, San Mateo, CA, 
      94402, USA.
FAU - Ishida, Kosuke
AU  - Ishida K
AD  - Clinical Development, Rakuten Medical Japan, K.K., Futako Tamagawa Rise Office, 
      2-21-1, Tamagawa, Setagaya-ku, Tokyo, Japan.
FAU - Hayashi, Ryuichi
AU  - Hayashi R
AD  - Department of Head and Neck Surgery, National Cancer Center Hospital East, 
      Kashiwa, Chiba, Japan.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20210624
PL  - Japan
TA  - Int J Clin Oncol
JT  - International journal of clinical oncology
JID - 9616295
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - *Antineoplastic Combined Chemotherapy Protocols
MH  - Cetuximab/therapeutic use
MH  - *Head and Neck Neoplasms/drug therapy
MH  - Humans
MH  - Immunotherapy
MH  - Japan
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - Squamous Cell Carcinoma of Head and Neck
PMC - PMC8449763
OTO - NOTNLM
OT  - Cetuximab-IR700DX conjugate
OT  - Light-activatable dye (IRDye(R)700DX)
OT  - Photoimmunotherapy
OT  - RM-1929 (cetuximab sarotalocan)
OT  - Recurrent head and neck squamous cell carcinoma
OT  - Tumor-targeted monoclonal antibodies
COIS- Makoto Tahara: research expenses (AstraZeneca, MSD, Bayer, Pfizer, Ono); lecturer 
      fee (Eisai, Merck Serono, BMS, Ono). Susumu Okano: Honoraria (Merck Serono, MSD, 
      Eisai, Ono, Bristol-Myers). Tomohiro Enokida: no conflicts to disclose. Yuri 
      Ueda: lecturer fee (Merck Serono, BMS). Takao Fujisawa: no conflicts to disclose. 
      Takeshi Shinozaki: lecturer fee (Rakuten Medical Inc). Toshifumi Tomioka: no 
      conflicts to disclose. Wataru Okano: no conflicts to disclose. Merrill A. Biel: 
      prior employment (Rakuten Medical Inc.); leadership (Rakuten Medical Inc.); stock 
      and other ownership interests (Rakuten Medical Inc.); travel, accommodation, 
      expenses (Rakuten Medical Inc.). Kosuke Ishida: employment (Rakuten Medical Inc; 
      Boehringer Ingelheim); stock and other ownership interests (Rakuten Medical 
      Inc.). Ryuichi Hayashi: lecturer fee (Rakuten Medical Inc).
EDAT- 2021/06/25 06:00
MHDA- 2021/09/22 06:00
PMCR- 2021/06/24
CRDT- 2021/06/24 12:30
PHST- 2021/02/24 00:00 [received]
PHST- 2021/06/03 00:00 [accepted]
PHST- 2021/06/25 06:00 [pubmed]
PHST- 2021/09/22 06:00 [medline]
PHST- 2021/06/24 12:30 [entrez]
PHST- 2021/06/24 00:00 [pmc-release]
AID - 10.1007/s10147-021-01960-6 [pii]
AID - 1960 [pii]
AID - 10.1007/s10147-021-01960-6 [doi]
PST - ppublish
SO  - Int J Clin Oncol. 2021 Oct;26(10):1812-1821. doi: 10.1007/s10147-021-01960-6. 
      Epub 2021 Jun 24.