臨床研究等提出・公開システム

Phase I/II Clinical Study of TAS0313 in Patients with Solid Tumor

TAS0313 Phase I/II study

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Cohort A (Dose-Escalation): In the 9mg and 27mg groups, 3/10 and 5/7 patients were male, respectively. The median age in both groups was 65 years, and ECOG performance status of 0 was observed in 5/10 and 3/7 patients. In the 9mg group, tumor types included pancreatic cancer (n=3), biliary tract cancer, breast cancer, lung cancer, ovarian cancer (n=1 each), and others (n=3). In the 27mg group, tumor types included biliary tract cancer, lung cancer, and pancreatic cancer (n=1 each), and others (n=4). Cohort B (Efficacy Exploration): 5/10 patients were male, with a median age of 56.5 years. Karnofsky Performance Status (KPS) was 80 in 5 patients and 90 in 4 patients. Histological subtypes included glioblastoma (n=8) and gliosarcoma (n=2). Cohort C1 (Urothelial Carcinoma, Immune Checkpoint Inhibitor-Naive): 31/36 patients were male, with a median age of 71.0 years. ECOG performance status of 0 was observed in 28 patients. Histological subtypes included bladder cancer (n=16), renal pelvic cancer (n=14), and ureteral cancer (n=6). Cohort C2 (Urothelial Carcinoma, Prior Pembrolizumab Treatment): 6/10 patients were male, with a median age of 65.5 years.

Cohort A: A total of 10 and 7 patients were enrolled in the 9mg and 27mg groups, respectively. The number of patients who received the investigational drug, and were included in the full analysis set (FAS), and the pharmacodynamics evaluable set was 10 and 7, respectively. The number of patients included the tolerability evaluable set was 8 and 6, respectively. Cohort B: Ten patients were enrolled. All received the investigational drug and were included in FAS, while 9 were included in the per-protocol set (PPS). Cohort C1: Thirty-six patients were enrolled. All received the investigational drug and were included in FAS. Cohort C2: Ten patients were enrolled. All received the investigational drug and were included in FAS.

Cohort A: Adverse drug reactions (ADRs) observed in >=2 patients included injection-site reactions in 60.0% of patients in the 9 mg group and 57.1% in the 27 mg group, and pyrexia in 28.6% of patients in the 27 mg group. No grade >=3 ADRs were reported. Cohort B: ADRs observed in >=2 patients included injection-site reactions (80.0%), pyrexia (70.0%), malaise, injection-site erythema, and injection-site pruritus (each 20.0%). Grade >=3 ADRs included anaphylactoid reaction in 10.0% of patients, and this event resolved immediately without any symptoms of shock and necessitated treatment discontinuation. Cohort C1: The ADRs observed in >=10% of patients were pyrexia and injection site reactions (each 41.7%) followed by injection site induration and malaise (each 16.7%). No grade >=3 ADRs were observed in >=10% of patients. Cohort C2: The most common ADRs were injection site reactions and pyrexia. No grade >=3 ADRs were observed in >=10% of patients.

Cohort A: No ADRs meeting the criteria for tolerability evaluation were observed in either the 9 mg or 27 mg groups. Cohort B: The objective response rate (ORR) was 22.2% (95% confidence interval [CI]: 2.5%-55.6%) in the PPS as assessed by RANO. Cohort C1: The ORR was 33.3% (95% CI: 18.6%-51.0%) including CR in 7 (19.4%) patients and PR in 5 (13.9%) in the FAS, as assessed by RECIST. Cohort C2: The ORR was 0% (95% CI: 0%-30.8%) in the FAS, as assessed by RECIST.

Cohort A: In the 9mg and 27mg groups, the disease control rate (DCR) was 20.0% and 28.6%, respectively. The median progression-free survival (PFS) was 1.8 months and 2.2 months, respectively. Cohort B: The DCR was 44.4% (95% CI: 13.7%-78.8%), the median duration of response (DOR) was 33.1 months, and the median PFS was 1.7 months (95% CI: 1.3-49.5) in the PPS. Cohort C1: The DCR was 66.7% (95% CI: 49.0%-81.4%), the median PFS was 5.0 months (95% CI: 2.4-14.2), and the median overall survival (OS) was not reached (FAS, RECIST*). Among patients with high TIL or CPS (TIL >=99 or CPS >=50%) and those with low TIL and CPS (TIL <99 and CPS <50%), the median PFS was 26.4 months and 3.7 months, respectively. Cohort C2: The DCR was 50.0% (95% CI: 18.7%-81.3%) (FAS, RECIST).

In Cohort A, no ADRs meeting the criteria for tolerability evaluation were observed in either the TAS0313 9mg or 27mg groups. In Cohort B, the monotherapy of TAS0313 at 27mg showed efficacy and acceptable safety in patients with recurrent glioblastoma. In Cohort C, the combination therapy of TAS0313 9mg and pembrolizumab showed efficacy in patients with locally advanced or metastatic urothelial carcinoma who had no prior treatment with immune checkpoint inhibitors and the main ADRs were manageable.

April. 02, 2024

https://aacrjournals.org/mct/article/23/4/532/741862/TAS0313-plus-Pembrolizumab-for-Post-Chemotherapy

No

Data will not be shared according to the Sponsor policy on data sharing. Taiho policy on data sharing may be found at https://www.taiho.co.jp/en/science/policy/clinical_trial_information_disclosure_policy/index.html.

Taiho Pharmaceutical Co., Ltd.

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toiawaseCD1@taiho.co.jp

Taiho Pharmaceutical Co., Ltd.

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+81-3-3293-2455

toiawase@taiho.co.jp

completed

Jan. 30, 2018

Interventional

open-label, non-randomized, multicenter Phase I/II study

treatment purpose

1-2

1. Provided written informed consent for participate in clinical trial
2. Has histologically or cytologically confirmed solid tumor(s) for which standard therapy has been performed
3. Has been confirmed to have any of the following genotypes by human leukocyte antigen (HLA) genotyping test: HLA-A*02:01, -A*02:06, -A*02:07, -A*11:01, -A*24:02, -A*31:01, and -A*33:03
4. Has a history of two or less chemotherapy regimens and meets any of the following (Cohort C1).
a) Received standard therapy including a platinum drug for unresectable locally advanced or metastatic urothelial carcinoma.
b) Received standard pre/post-operative adjuvant therapy including a platinum drug for localized muscle-invasive urothelial carcinoma, which was confirmed to recur or progress within 12 months after the end of the therapy.
5. Has demonstrated disease progression after pembrolizumab for unresectable locally advanced or metastatic urothelial carcinoma (Cohort C2).

1. Has serious diseases or conditions
2. Has a history of hypersensitivity to drugs in classes related to TAS0313, any excipient of TAS0313
3. Pregnant or lactating women or women of child-bearing potential who have a positive pregnancy test (urine or serum) within seven days prior to enrollment
4. Has received prior therapy with immunotherapy agents (Cohort C1)
5. Has received prior therapy with immunotherapy agents and was discontinued from that treatment due to irAE (Cohort C2)

Both

Solid tumor (urothelial carcinoma, and so on)

investigational material(s)
Generic name etc : TAS0313
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : In Cohort A and B, TAS0313 is administered.
In Cohort C (urothelial carcinoma cohort), TAS0313 is administered with pembrolizumab.
TAS0313 is subcutaneously administered near the lymph node on Days 1, 8, and 15 of Cycles 1 and 2 and on Day 1 of Cycle 3 or later, assuming that each cycle consists of 21 days.

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

safety
efficacy
Tolerability, Safety, Efficacy
NCI CTCAE v4.03
RECIST Version1.1
iRECIST
RANO for High grade glioma
iRANO

pharmacodynamics
pharmacogenomics
pharmacodynamics, pharmacogenomics

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Oct. 31, 2018