UMIN-CTR Clinical Trial

Public title

All-Patient General Drug Use Surveillance of Rozlytrek Capsule
-ROS1 fusion gene-positive unresectable advanced or recurrent non-small cell lung cancer-

Acronym

All-Patient General Drug Use Surveillance of Rozlytrek Capsule
-ROS1 fusion gene-positive unresectable advanced or recurrent non-small cell lung cancer-

Scientific Title

All-Patient General Drug Use Surveillance of Rozlytrek Capsule
-ROS1 fusion gene-positive unresectable advanced or recurrent non-small cell lung cancer-

Scientific Title:Acronym

All-Patient General Drug Use Surveillance of Rozlytrek Capsule
-ROS1 fusion gene-positive unresectable advanced or recurrent non-small cell lung cancer-

Region

Japan

Condition

ROS1 fusion gene-positive unresectable advanced or metastatic non-small cell lung cancer

Classification by specialty

Pneumology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

The primary objectives are to evaluate the following during clinical use of Rozlytrek.
1.Type and time of onset of early symptoms of cognitive disorders (e.g., cognitive disorder, confusional state, mental status changes, memory impairment, hallucination) and ataxia
2.Action taken with Rozlytrek for and outcome of cognitive disorders (e.g., cognitive disorder, confusional state, mental status changes, memory impairment, hallucination) and ataxia
3.Incidence of cardiac disorders (excluding prolonged QT), prolonged QT, syncope, and interstitial lung disease
4.Incidence of serious adverse events not defined in the safety specification
5.Investigator-assessed response rate
Safety concerns defined in the safety specification: Cognitive disorders/ataxia, cardiac disorders (excluding prolonged QT), prolonged QT, syncope, interstitial lung disease

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Safety
1.Incidence of early symptoms of cognitive disorders or ataxia by type
2.Time of onset of early symptoms of cognitive disorders or ataxia (e.g., basic statistics)
3.Proportion of patients requiring action with respect to Rozlytrek (e.g., treatment interruption, treatment discontinuation) at onset of cognitive disorder or ataxia
4.Outcome rate (e.g., recovered, improved) by action taken with Rozlytrek (treatment interruption, treatment discontinuation) at onset of cognitive disorder or ataxia
5.Incidence of ADRs by type (by MedDRA PT, by safety concern defined in the safety specification)
Effectiveness:
1.Investigator-assessed response rate (Assess response using RECIST.)
2.Investigator-assessed response rate in patients with ROS1 fusion gene mutations (Assess response using RECIST.)

Key secondary outcomes

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Patients eligible for enrollment: All patients with ROS1 fusion gene-positive unresectable advanced or recurrent non-small cell lung cancer who are planning to use Rozlytrek during the enrollment period.
Patients eligible for case report form (CRF) collection: All patients eligible for enrollment who receive Rozlytrek
CRFs will be collected for all patients with ROS1 fusion gene-positive unresectable advanced non-small cell lung cancer who receive Rozlytrek. Data will also be collected retrospectively from patients with ROS1 fusion gene-positive unresectable advanced non-small cell lung cancer who receive Rozlytrek before conclusion of the agreement for this surveillance study.

Key exclusion criteria

None

Target sample size

200

Name of lead principal investigator

1st name	Makoto
Middle name
Last name	Nomura

Organization

Chugai Pharmaceutical Co. Ltd.

Division name

Safety Science Dept.

Zip code

1038324

Address

1-1 Nihonbashi-muromachi 2-chome, Chuo-ku Tokyo, Japan

TEL

03-3281-6611

Email

nomuramkt@chugai-pharm.co.jp

Name of contact person

1st name	Ryousuke
Middle name
Last name	Harada

Organization

Chugai Pharmaceutical Co. Ltd.

Division name

Real World Data Science Dept.

Zip code

1038324

Address

1-1 Nihonbashi-muromachi 2-chome, Chuo-ku Tokyo, Japan

TEL

03-3281-6611

Homepage URL

Email

haradarus@chugai-pharm.co.jp

Institute

Chugai Pharmaceutical Co. Ltd.

Institute

Department

Personal name

Organization

Chugai Pharmaceutical Co. Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

None

Address

None

Tel

None

Email

None

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2022

Year

01

Month

13

Day

URL releasing protocol

not applicable

Publication of results

Unpublished

URL related to results and publications

not applicable

Number of participants that the trial has enrolled

276

Results

269 patients included in safety analysis
Sex: male, 34.57% (n = 93); median age: 66.0 years

Percentage of patients with adverse reactions *: 53.15% (143 patients) * Adverse reactions were tabulated among adverse events of "Safety specifications, serious events other than safety specifications"
Serious adverse reactions: incidence 36.80% (99 patients)

Results date posted

2024

Year

07

Month

17

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Patient characteristics (analysis set: safety analysis set: 269 patients)
Sex: Male 34.57% (93 patients), female 65.42% (176 patients) no pregnancy (during treatment period)
Age: Median 66.0 years, < 15 years None, >- 15 and < 65 years 45.35% (122 patients), >- 65 years 54.64% (147 patients)

Participant flow

This survey was conducted at 203 contract sites *, and 276 patients were registered from 193 sites * during the registration period. There were no patients whose CRFs could not be collected, and CRFs were collected from 276 patients at 193 facilities * 5.
*: The number of study sites is shown as the total number of study sites if a separate contract is concluded with each department at the same study site.

Of the 276 patients for whom the CRF was collected, 269 patients were included in the safety analysis set after excluding 6 patients with duplicate data (hospital transfer) and 1 patient with unconfirmed safety data (adverse event).
A total of 260 patients were included in the ROS1 efficacy analysis set after excluding 8 previously treated patients and 1 patient whose efficacy could not be calculated from the 269 patients in the safety analysis set.

Adverse events

Occurrence of ADRs
Incidence of adverse reactions *: 53.15% (143 patients)
*: Adverse reactions were tabulated among adverse events in the "Safety specifications, serious events other than safety specifications" subject to collection and tabulation in this survey.
Serious adverse reactions: incidence 36.80% (99 patients), number of events 162
Deaths for which a causal relationship to this drug could not be ruled out: 3 events in 2 subjects (Lung disorder, acute cardiac failure and cardiomyopathy)

Outcome measures

Safety Results
Occurrence of ADRs
Incidence of adverse reactions *: 53.15% (143 patients)
*: Adverse reactions were tabulated among adverse events in the "Safety specifications, serious events other than safety specifications" subject to collection and tabulation in this survey.
Serious adverse reactions: incidence 36.80% (99 patients), number of events 162
Deaths for which a causal relationship to this drug could not be ruled out: 3 events in 2 subjects (Lung disorder, acute cardiac failure and cardiomyopathy)

Efficacy Results
Response rate assessed by primary physician (analysis set: ROS1 efficacy analysis set: 260 patients)
Response evaluation by primary physician: Complete response (CR) 3.07% (8 patients), partial response (PR) 35.76% (93 patients), progressive disease (PD) 25.38% (66 patients), stable disease (SD) 19.61% (51 patients), non-CR/non-PD (Non-CR/non-PD) 2.30% (6 patients), not evaluable (NE) 13.84% (36 patients)
Overall response rate (95% CI): 38.84% (32.88 -45.06)
Response rate (95% CI) by line of therapy: 70.83% (55.93 -83.04) (48 subjects) in the first-line therapy, 34.73% (25.25 -45.19 subjects) (95 subjects) in the second-line therapy, 26.82% (14.22 -42.94 subjects) (41 subjects) in the third-line therapy, 30.55% (16.34 -48.10 subjects) (36 subjects) in the fourth-line therapy, 30.00% (16.56 -46.53 subjects) (40 subjects) in the fifth-line and subsequent therapies

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2020

Year

02

Month

17

Day

Date of IRB

2020

Year

02

Month

17

Day

Anticipated trial start date

2020

Year

02

Month

17

Day

Last follow-up date

2023

Year

01

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

None

Registered date

2022

Year

01

Month

13

Day

Last modified on

2024

Year

07

Month

17

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045060