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Phase I study of RO6874281 in patients with advanced solid tumors

Phase I study of RO6874281 in patients with advanced solid tumors

11

The median age was 56.0 years (range: 29~71 years), and there were 3 patients aged >= 65 years. All patients were male and ECOG PS of 0 was 10 patients and ECOG PS of 1 was 1 patient at baseline.

Three patients were enrolled in Stage 1 Cohort 1 (10 mg treatment group), 5 in Stage 1 Cohort 2 (15/20 mg treatment group), and 3 in Stage 2 Cohort A (10 mg + atezolizumab 840 mg treatment group).

In Stage 1 Cohort 1, 133 adverse events were reported in 3 of 3 patients, and adverse drug reactions were reported in 3 of 3 patients. No serious adverse events were reported. In Stage 1 Cohort 2, 152 adverse events were reported in 5 of 5 patients and adverse drug reactions were reported in 5 of 5 patients. Serious adverse events occurred in 2 of the 5 patients. In Stage 2 Cohort A, 118 adverse events occurred in 3 of 3 patients, and adverse drug reactions occurred in 3 of 3 patients. Serious adverse events occurred in 1 of the 3 patients.

A DLT of Grade 3 hypotension was reported in 1 patient in Stage 1 Cohort 2. Pharmacokinetic analyses in Stage 1 Cohort 1, Stage 1 Cohort 2, and Stage 2 Cohort A showed that following a single dose of RO6874281 (Cycle 1Day 1), median (min-max) Tmax was 3.67 h (2.17-4.20 h), 3.05 h (2.20-4.00 h), and 2.12 h (2.12-2.20 h), respectively; mean +/- SD for Cmax was 4.41 +/- 0.905 mcg/mL, 4.36 +/- 0.508 mcg/mL, and 5.15 +/- 1.64 mcg/mL, respectively; mean +/- SD for AUClast was 115 +/- 26.3 h*mcg/mL, 119 +/- 22.5 h*mcg/mL, and 116 +/- 29.0 h*mcg/mL, respectively; and mean +/- SD for t1/2 was 12.6 +/- 5.01 h, 9.63 +/- 0.843 h, and 10.0 +/- 2.18 h, respectively.

Of the 11 patients in Stage 1 and 2, no patient had a best overall response not requiring confirmation of complete response, and 1 patient in Stage 1 Cohort 1 had a partial response.

While RO6874281 monotherapy (RO6874281 10 mg QW/Q2W monotherapy) and combination therapy with atezolizumab (RO6874281 10 mg QW + atezolizumab 840 mg Q2W combination therapy) were confirmed to be safe and tolerable, the tolerability of increasing doses of RO6874281 monotherapy (RO6874281 15/20 mg QW/Q2W monotherapy) could not be confirmed since enrollment was terminated early. Pharmacokinetic parameters were similar across stages and cohorts.

Yes

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Chugai Pharmaceutical Co., Ltd.

1-1 NIHONBASHI-MUROMACHI 2-CHOME, CHUO-KU, Tokyo

clinical-trials@chugai-pharm.co.jp

Chugai Pharmaceutical Co., Ltd.

1-1 NIHONBASHI-MUROMACHI 2-CHOME, CHUO-KU, Tokyo

+81-120189706

clinical-trials@chugai-pharm.co.jp

completed

Oct. 28, 2019

Interventional

Open-label, singlecenter, dose-escalation study

treatment purpose

1

- ECOG Performance Status of 0 or 1
- Histologically or cytologically documented solid tumors
- Evaluable lesion by image

- Meningeal metastasis or metastasis to the central nervous system requiring treatment or accompanied by symptoms
- History or complication of autoimmune disease
- History of severe adverse reaction by treatment with previous cancer immunotherapy

Both

Solid Tumor

investigational material(s)
Generic name etc : RO6874281
INN of investigational material : simlukafusp alfa
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : intravenous infusion at the dose of 10 mg, 15 mg or 20 mg, weekly or biweekly
Generic name etc : Atezolizumab
INN of investigational material : Atezolizumab
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : intravenous infusion at the dose of 840 mg, biweekly

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

safety
pharmacokinetics
other
other (tolerability)
Observation / inspection

efficacy
exploratory
Observation / inspection

May. 22, 2019