PMID- 36268537
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221022
IS  - 2666-3643 (Electronic)
IS  - 2666-3643 (Linking)
VI  - 3
IP  - 11
DP  - 2022 Nov
TI  - A Phase 1, Open-Label, Dose-Escalation Study of L-DOS47 in Combination With 
      Pemetrexed Plus Carboplatin in Patients With Stage IV Recurrent or Metastatic 
      Nonsquamous NSCLC.
PG  - 100408
LID - 10.1016/j.jtocrr.2022.100408 [doi]
LID - 100408
AB  - INTRODUCTION: L-DOS47, a targeted urease-anti-CEACAM6 immunoconjugate, alters the 
      acidity of the tumor microenvironment by increasing local ammonia production. 
      In vitro, the cytotoxic effects of L-DOS47 were additive when combined with 
      pemetrexed and carboplatin. METHODS: This phase I, open-label, dose-escalation 
      study evaluated the safety and tolerability of up to four cycles of L-DOS47 
      (administered on days 1, 8, and 15 of each cycle at doses ranging from 0.59 to 
      9.0 mug/kg) combined with pemetrexed and carboplatin in patients with stage IV 
      nonsquamous NSCLC. Continued L-DOS47 treatment after the fourth cycle was allowed 
      at the treating physicians' discretion. RESULTS: A total of 14 patients received 
      at least one dose of L-DOS47. Overall, L-DOS47 was well tolerated. Grade greater 
      than or equal to 3 adverse events (AEs) were typically neutropenia related. Two 
      grade greater than or equal to 3 AEs and no serious AEs were considered at least 
      possibly related to L-DOS47. No dose-limiting toxicities were reported, so the 
      maximum tolerated dose was not reached. The objective response rate was 41.7% 
      with a median duration of response of 187 days. Clinical benefit was observed in 
      75.0% of the patients. After the first dose, L-DOS47 systemic exposure increased 
      in a generally dose-proportional manner but decreased substantially with repeat 
      dosing. Anti-L-DOS47 antibodies were detectable in 13 of 14 patients by cycle 2 
      with titers typically increasing with continued treatment. There was an apparent 
      association between best overall response rate and highest anti-L-DOS47 antibody 
      titer measured. CONCLUSIONS: L-DOS47 combined with standard pemetrexed and 
      carboplatin chemotherapy is well tolerated in patients with recurrent or 
      metastatic nonsquamous NSCLC at doses up to 9.0 mug/kg.
CI  - (c) 2022 The Authors.
FAU - Piha-Paul, Sarina
AU  - Piha-Paul S
AD  - Department of Investigational Cancer Therapeutics, University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
FAU - Simon, George
AU  - Simon G
AD  - H. Lee Moffitt Cancer Center, Tampa, Florida.
FAU - Belani, Chandra P
AU  - Belani CP
AD  - Penn State Hershey Cancer Institute, Hershey, Pennsylvania.
FAU - Chao, Heman
AU  - Chao H
AD  - Helix BioPharma Corp., Toronto, Ontario, Canada.
FAU - Gaspar, Kim
AU  - Gaspar K
AD  - Helix BioPharma Corp., Toronto, Ontario, Canada.
FAU - Lee, Brenda
AU  - Lee B
AD  - Helix BioPharma Corp., Toronto, Ontario, Canada.
FAU - Dowlati, Afshin
AU  - Dowlati A
AD  - University Hospitals Seidman Cancer Center and Case Western Reserve University, 
      Cleveland, Ohio.
LA  - eng
PT  - Journal Article
DEP - 20220916
PL  - United States
TA  - JTO Clin Res Rep
JT  - JTO clinical and research reports
JID - 101769967
PMC - PMC9576893
OTO - NOTNLM
OT  - Carboplatin
OT  - Immunotherapy
OT  - L-DOS47
OT  - Non-small cell lung cancer
OT  - Pemetrexed
EDAT- 2022/10/22 06:00
MHDA- 2022/10/22 06:01
PMCR- 2022/09/16
CRDT- 2022/10/21 03:16
PHST- 2022/08/09 00:00 [received]
PHST- 2022/09/02 00:00 [accepted]
PHST- 2022/10/21 03:16 [entrez]
PHST- 2022/10/22 06:00 [pubmed]
PHST- 2022/10/22 06:01 [medline]
PHST- 2022/09/16 00:00 [pmc-release]
AID - S2666-3643(22)00132-1 [pii]
AID - 100408 [pii]
AID - 10.1016/j.jtocrr.2022.100408 [doi]
PST - epublish
SO  - JTO Clin Res Rep. 2022 Sep 16;3(11):100408. doi: 10.1016/j.jtocrr.2022.100408. 
      eCollection 2022 Nov.