A study of tucatinib with trastuzumab and mFOLFOX6 versus standard of care treatment in first-line HER2+ metastatic colorectal cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Seagen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Nov 2022 → ongoing

Decision date (initial)

2024-06-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Seagen Inc

External identifiers

EU CT number

2024-514180-25-00

EudraCT number

2021-002672-40

ClinicalTrials.gov

NCT05253651

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Therapy, Safety, Efficacy

To compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST v1.1) according to blinded independent central review (BICR) assessment between treatment arms

Secondary objectives 11

1. To compare overall survival (OS) between treatment arms
2. To compare confirmed objective response rate (cORR) per RECIST v1.1 according to BICR assessment between treatment arms
3. To assess PFS per RECIST v1.1 according to investigator (INV) assessment
4. To evaluate cORR per RECIST v1.1 according to INV assessment
5. To evaluate duration of response (DOR) per RECIST v1.1 according to BICR assessment
6. To evaluate DOR according to INV assessment
7. To evaluate time from randomization to disease progression on next-line treatment or death from any cause (PFS2)
8. To assess the overall safety profiles by the treatment arms
9. To evaluate the pharmacokinetics (PK) of tucatinib
10. To assess the change from baseline in selected items of the global health status/quality of life (QoL), physical functioning, and appetite loss by treatment arms using the European Organization for Research and Treatment of Cancer Quality of Life 30-item core questionnaire (EORTC QLQ-C30)
11. To assess the time to meaningful change in global health status/QoL, physical functioning and appetite loss by treatment arms using the EORTC QLQ-C30

Conditions and MedDRA coding

unresectable or metastatic HER2+ colorectal cancer

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Danish Medicines Agency, Agencia Espanola De Medicamentos Y Productos Sanitarios

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Have histologically and/or cytologically documented adenocarcinoma of the colon or rectum, which is locally advanced unresectable or metastatic
2. Participants must be willing and able to provide the most recently available formalin-fixed paraffin-embedded tumor tissue blocks obtained prior to treatment initiation, to a sponsor-designated central laboratory for biomarker analysis. If archival tissue is not available, then a newly-obtained baseline biopsy of an accessible tumor lesion is required within 35 days prior to the Cycle 1 Day 1 timeframe. Biopsy must provide adequate tissue for analysis; the following biopsy types are acceptable: resection, excision, punch (skin lesions only) and core needle biopsies.
3. Have HER2+ disease as determined by tissue-based investigational HER2 IHC and ISH assays performed at a sponsor-defined central laboratory. HER2 amplification will be determined using ASCO/CAP guidelines for gastric and gastroesophageal cancer with IHC 3+ or IHC 2+/ISH+ result.
4. H4. Have RAS WT disease as determined by local or central testing. Central testing may only be used with Medical Monitor approval if local testing is not available or when otherwise deemed necessary. For central RAS analysis, tissue sample must be analyzed within 1 year of biopsy date.
5. Have radiographically measurable disease per RECIST v1.1 according to INV assessment, with at least one site of disease that is measurable and that has not been previously irradiated; or, if the subject has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation
6. Have ECOG Performance Status (PS) of 0 or 1
7. CNS Inclusion: a. No evidence of brain metastases; b. Previously treated brain metastases which are asymptomatic.

Exclusion criteria 6

1. Have previously received any systemic anticancer therapy for CRC in the metastatic setting or have participated in any interventional clinical trial for CRC in the metastatic setting; note that subjects may have received a maximum of 2 doses of mFOLFOX6 in the locally advanced/unresectable or metastatic setting prior to randomization. Participants may have received prior chemotherapy for CRC in the adjuvant setting provided that it was completed >6 months prior to enrollment.
2. Have previously received radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of SRS). SubjectsParticipants who have received prior radiation therapy must have recovered to baseline from any treatment-related adverse events (AEs). Participants Subjects who have received palliative radiotherapy for symptomatic metastases may enter the study without a washout period provided that the subject has recovered from any treatment-related AEs.
3. Have previously been treated with anti-HER2 therapy
4. Have ongoing ≥ Grade 2 diarrhea of any etiology
5. Inability to swallow pills or any significant GI disease which would preclude the adequate oral absorption of medications
6. Participants with active CNS metastases (irradiated or resected lesions are permitted). See Inclusion Criteria for details. Participants with carcinomatous meningitis are excluded without exception.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS per BICR is defined as the time from the date of randomization to the BICR assessment of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first

Secondary endpoints 9

1. OS, defined as time from randomization to death from any cause (key secondary endpoint)
2. cORR per BICR is defined as the proportion of participants with confirmed CR or PR according to RECIST v1.1, as assessed by BICR. (key secondary endpoint)
3. PFS per INV is defined as time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first
4. cORR per INV is defined as the proportion of participants with confirmed CR or PR according to RECIST v1.1, as assessed by investigators.
5. DOR is defined as time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of disease progression per RECIST v1.1 or death from any cause, whichever occurs earlier.
6. DOR per investigator is based on investigator response assessment and DOR per BICR is based on BICR response.
7. Time to second progression or death (PFS2) is defined as the time from randomization to disease progression on the next-line of therapy, or death from any cause, whichever occurs first
8. Individual plasma tucatinib concentrations will be used for PK assessments
9. Change from baseline will be measured for the following PROs scales: global health status/QoL (EORTC QLQ-C30 items 29 and 30) and physical functioning (EORTC QLQ-C30 items 1-5) and time to meaningful change, defined as the time from baseline to the first onset of a ≥10-point changes from baseline in global health status/QoL (EORTC QLQ-C30 items 29 and 30), physical functioning (EORTC QLQ-C30 items 1-5)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Seagen Inc.

Sponsor organisation

Seagen Inc.

Address

21823 30th Drive Southeast

City

Bothell

Postcode

98021-3907

Country

United States

Scientific contact point

Organisation

Seagen Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Seagen Inc.

Contact name

Clinical Medical Lead

Third parties 19

Locations

14 EU/EEA countries · 115 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 199 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

16 submissions — initial application plus substantial / non-substantial modifications