A Phase1b Dose Escalation Study of Recombinant Circularly Permuted TRAIL in Patients With Relapsed or Refractory Multiple Myeloma.
Am J Clin Oncol
; 41(10): 1008-1014, 2018 10.
Article
in En
| MEDLINE
| ID: mdl-28930776
ABSTRACT
OBJECTIVES:
Circularly permuted tumor necrosis factor-related apoptosis-inducing ligand (CPT), or CPT, is a novel antitumor drug candidate. This phase 1b study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of single-agent CPT in patients with relapsed or refractory multiple myeloma (RRMM), and aimed to identify the recommended dose for the phase 2 study. MATERIALS ANDMETHODS:
Patients received single or multiple doses (once daily for 5 consecutive days per 21-d cycle) of CPT intravenous infusion at doses of 5, 6.5, 8, 10, and 15 mg/kg, to determine the maximum tolerated dose, dose-limiting toxicities, safety, and tolerability. PK were evaluated. Preliminary efficacy was assessed after each treatment cycle.RESULTS:
Twenty-nine RRMM patients received CPT. Neither the dose-limiting toxicity nor the maximum tolerated dose were identified. The most common treatment-related adverse events were liver enzyme elevations (eg, elevation of aspartate aminotransferase and alanine aminotransferase), hematological abnormalities (eg, leukopenia and neutropenia), fever, fatigue, and vomiting. CPT had a terminal half-life of 0.90 to 1.27 hours at the 5 dose levels, and no accumulation was observed with repeated doses. Safety and PK profiles were similar across the 5 dose cohorts. The overall response rate (complete and partial response) was 18.5%. The clinical benefit rate (complete, partial, and minimal response) was 33.3%. Sixteen patients did not respond to CPT (no change and progressive disease). Patients treated with higher doses of CPT appeared to have better responses.CONCLUSIONS:
CPT was safe and well tolerated by RRMM patients, and doses between 8 and 15 mg/kg were recommended for the phase 2 study.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Recombinant Proteins
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Salvage Therapy
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Drug Resistance, Neoplasm
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TNF-Related Apoptosis-Inducing Ligand
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Multiple Myeloma
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Neoplasm Recurrence, Local
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Antineoplastic Agents
Type of study:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
Limits:
Aged
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Aged80
/
Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Am J Clin Oncol
Year:
2018
Document type:
Article