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A Phase I study of tocilizumab plus gemcitabine/nab-paclitaxel in patient with gemcitabine/nab-paclitaxel-refractory metastatic pancreatic cancer

TCZ+GN Study

10

Among 10 registered patients, the mean (max - min) of age was 64 (48-76), and 6 were male and 4 were female.

10 patients enrolled in the dose-finding and expansion cohorts completed Cycle 1 and comprised the safety population and full analysis set. Four patients transitioned to additional cycles. Patient demographic and baseline characteristics are shown in table 1. The median (IQR) age was 64 (48-76) years, with 6 male and 4 female patients. Primary sites of pancreatic tumour were the head (n=4), body (n=3), and tail (n=3). Biliary drainage was present in half of all cases. Prior regimens were comprised of GEM+nab-PTX in all patients, variously combined with modified FOLFIRINOX in four patients, the 5-fluouracil prodrug S-1 in three patients, and gemcitabine + erlotinib in one patient. In four patients who received an additional cycle, three patients continued treatment for 12 weeks or more. Overall, the median (min-max) duration of treatment was 34.5 (30-169) days

Treatment-emergent adverse events (TEAEs) were found in eight patients (80%) and the most common TEAE was decreased neutrophil count (n=5, 7 events). Grade 3 or higher events occurred in six patients (60%) and the most common Grade 3 or higher TEAE was decreased neutrophil count (50%). TEAEs leading to drug withdrawal were decreased neutrophil count (n=5, 7 events) and increased aspartate aminotransferase (n=1, 1 event), which were resolved within two weeks. In Cycle 1, drug withdrawal due to decreased neutrophil count occurred in two patients. TEAE leading to dose reduction, serious TEAEs or deaths attributed to TEAEs were not recorded.

The recommended dosage of TCZ was determined as 8 mg/kg. No DLTs occurred in the three patients in the dose-finding cohort. As the study duration was limited, there was no opportunity to increase the dose of GEM/nab-PTX.

The best overall effect was PR in one patient and the objective response rate (95%CI) was 10.0 (0.3-44.5)%. Further, the disease control rate (95%CI) was 80.0 (44.4-97.5)%, which consisted of seven patients with stable disease and one patient with PR. Disease control was maintained in six patients for 8 weeks or more. The median (95%CI) PFS in all enrolled patients was 2.7 (1.2-3.7) months. 'The median (IQR) global symptom score and global QOL score of the MDASI-J changed by -0.3 (-0.8, 1.1) and 0.9 (0.0, -2.2), respectively, from baseline to Day 28 of Cycle 1. In all three patients without cachexia at baseline, global symptom scores and global QOL scores were not increased (not worsened), whereas only 2 of 7 patients with cachexia showed an increase (worsening) in both global symptom scores and global QOL scores in Cycle 1.

TCZ+GEM/nab-PTX appears to have a manageable safety profile and preliminary antitumour activity in patients with GEM/nab-PTX-refractory MPC.

No

National Cancer Center Hospital East

6-5-1 Kashiwanoha,Kashiwa,Chiba,Japan 277-8577

tczgn_core@east.ncc.go.jp

National Cancer Center Hospital East

6-5-1 Kashiwanoha,Kashiwa,Chiba,Japan 277-8577

+81-4-7133-1111

tczgn_core@east.ncc.go.jp

completed

May. 20, 2019

Interventional

An open-label, phase I study

treatment purpose

1

1. Written informed consent for participation in the study is obtained at the discretion of the patient.
2. Metastatic pancreatic cancer with histologically or cytologically confirmed diagnosis of adenocarcinoma
3. Patients with progressed pancreatic cancer after treatment with GEM/nab-PTX achieved complete, partial response (PR) by the Response Evaluation Criteria in Solid Tumours (RECIST) guideline version 1.1, or equivanlent to PR (more than 20% tumor shrinkage or more than 50% reduction of tumor marker, such as CA19-9) for unresectable or recurrent pancreatic cancer
4. GEM (750 mg/m2) and nabPTX (100 mg/m2) is judged to be tolerable when GEM/nabPTX is rechallenged
5. Measurable disease based on RECIST version 1.1.
6. serum CRP level >=0.5 to <10.0 mg/dL

1. Severe effusion or edema
2. Symptomatic brain metastasis
3. Active concomitant malignancy
4. Prior choledochojejunostomy
5. Transfusion within 4 weeks before enrollment
6. Major surgery excluding biliary drainage percutaneously or endoscopically within 4 weeks before enrollment
7. Scheduled surgery during the study treatment
8. Prior IL-6 signal blocker treatments including JAK inhibitors
9. Prior immunotherapy including cancer vaccine, immune-checkpoint inhibitor, and so on
10. Prior treatment with biologics including TCZ, trastuzumab, Infliximab, etanersept and adalimumab within 4 weeks before enrollment
11. Active infectious diseases requiring systemic administration of antibiotics, antivirals, antifungals, etc.

Both

Pancreatic cancer

investigational material(s)
Generic name etc : Tocilizumab (Genetical Recombination)
INN of investigational material : tocilizumab
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : Tocilizumab 4 mg/kg or 8 mg/kg intraveniously, in a 28 day-cycle.

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

safety
- Frequency of adverse events
- Occurrence of dose limiting toxicity

efficacy
pharmacokinetics
- Pharmacokinnetics of TCZ
- Objective response rate: ORR
- Disease control rate: DCR
-Progression-free survival: PFS
-MDASI-J; Symptom scores and Interference scores

+81-4-7133-1111

Mar. 20, 2019