Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers

Cholangiocarcinoma Clinical Trial

Official title:

A Phase 1b/2 Dose Escalation and Expansion Study of Tucatinib in Combination With Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04430738
• Other study ID #: SGNTUC-024
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 15, 2020
• Est. completion date: October 31, 2025

Study information

• Verified date: April 2024
• Source: Seagen Inc.
• Contact: Seagen Trial Information Support
• Phone: 8663337436
• Email: clinicaltrials[@]seagen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial studies tucatinib to find out if it is safe when given with trastuzumab and other anti-cancer drugs (pembrolizumab, FOLFOX, and CAPOX). It will look at what side effects happen when participants take this combination of drugs. A side effect is anything the drug does other than treating cancer. It will also look at whether tucatinib works with these drugs to treat certain types of cancer. The participants in this trial have HER2-positive (HER2+) cancer in their gut, stomach, intestines, or gallbladder (gastrointestinal cancer).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: October 31, 2025
• Est. primary completion date: May 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants must have an unresectable or metastatic solid malignancy that is

histologically or cytologically confirmed to be one of the tumor types listed below:

• Cohorts 1A, 1B, 1C, and 1D
• CRC
• Gastric adenocarcinoma
• GEJ adenocarcinoma
• Esophageal adenocarcinoma
• Cholangiocarcinoma
• Gallbladder carcinoma
• Cohorts 1E, 1F, 1G, and 2A
• Gastric adenocarcinoma
• GEJ adenocarcinoma
• Esophageal adenocarcinoma
• Cohort 2B
• CRC
• Participants must be candidates to receive an oxaliplatin-based regimen as part of their standard-of-care treatment for all cohorts, except Cohort 1G.
• HER2+ disease, as determined by historic or local laboratory testing
• Phase 1b cohorts: measurable or non-measurable disease according to RECIST v1.1 as determined by the investigator
• Phase 2 cohorts: measurable disease according to RECIST v1.1 as determined by the investigator
• Eastern Cooperative Oncology Group Performance Status score of 0 or 1.

Exclusion Criteria:

• History of known hypersensitivity to planned study treatment
• Known to be positive for Hepatitis B or C
• For Cohorts 2A and 2B: prior anti-HER2 therapies
• For Cohorts 1E, 1F, 1G, 2A: Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE) There are additional inclusion criteria. The study center will determine if criteria for participations are met.

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Cholangiocarcinoma
• Colorectal Carcinoma
• Colorectal Neoplasms
• Esophageal Adenocarcinoma
• Gallbladder Carcinoma
• Gastric Adenocarcinoma
• Gastrointestinal Neoplasms
• GEJ Adenocarcinoma

Intervention

Drug:
• tucatinib
For Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.
• trastuzumab
Cohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter.
• oxaliplatin
85 mg/m^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m^2 given every 3 weeks.
• leucovorin
200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m^2 given IV every 2 weeks. Part of FOLFOX regimen.
• fluorouracil
400 mg/m^2 (IV bolus after leucovorin) and/or 2400 mg/m^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.
• capecitabine
1000 mg/m^2 is taken twice per day orally on Days 1-14 of each 3 week cycle. Part of CAPOX regimen.
• pembrolizumab
400 mg given by IV on day 1 of cycle 1, then every 6 weeks.

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo-ku	Other
Japan	National Cancer Center Hospital East	Kashiwa-shi	Other
Japan	St. Marianna University School of Medicine	Kawasaki-shi	Other
Japan	The Cancer Institute Hospital of Japanese Foundation for Cancer Research	Koto-ku	Other
Japan	Aichi Cancer Center	Nagoya-shi	Other
Japan	Osaka International Cancer Institute	Osaka	Other
Japan	Kindai University Hospital	Osakasayama-Shi	Other
United States	New Mexico Cancer Center	Albuquerque	New Mexico
United States	University of Colorado Hospital / University of Colorado	Aurora	Colorado
United States	Gabrail Cancer Center Research, LLC	Canton	Ohio
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic, The	Cleveland	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	SCL Health Good Samaritan Medical Center Cancer Centers of Colorado	Lafayette	Colorado
United States	Stanford Cancer Center / Blood and Marrow Transplant Program	Palo Alto	California
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Washington University in St Louis	Saint Louis	Missouri
United States	Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Johns Hopkins Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Seagen Inc.

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of renal dose-limiting toxicities (DLTs) (Cohorts 1A and 1B)		Up to one month; 2 cycles after receiving all study treatment (each cycle is 14 days)
Primary	Incidence of adverse events (AEs) (Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B)	An AE is defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.	Up to approximately 12 months
Primary	Incidence of laboratory abnormalities (Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B)		Up to approximately 12 months
Primary	Incidence of DLTs (Cohorts 1C, 1D, 1E, 1F, and 1G)		Up to approximately 12 months
Primary	Incidence of dose alterations (Cohort 1D)		Up to approximately 12 months
Secondary	Incidence of AEs (Cohorts 1A and 1B)	An AE is defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.	Up to approximately 12 months
Secondary	Incidence of laboratory abnormalities (Cohorts 1A and 1B)		Up to approximately 12 months
Secondary	Change in glomerular filtration rate (GFR) from baseline through 2 cycles of combination therapy (Cohorts 1A and 1B)	To be summarized using descriptive statistics	Up to approximately 6 weeks
Secondary	Pharmacokinetic (PK) parameter of tucatinib - AUClast (Cohorts 1A and 1B)	To be summarized using descriptive statistics	Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)
Secondary	PK parameter of tucatinib - Cmax (Cohorts 1A and 1B)	To be summarized using descriptive statistics	Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)
Secondary	PK parameter of tucatinib - Ctrough (Cohorts 1A, 1B, 1C, 1E, 1F, and 1G)	To be summarized using descriptive statistics	Up to approximately 2.5 months; through predose of Cycle 6, Day 1
Secondary	PK parameter of tucatinib - Tmax (Cohorts 1A and 1B)	To be summarized using descriptive statistics	Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)
Secondary	PK parameter of oxaliplatin - AUClast (Cohorts 1A and 1B)	To be summarized using descriptive statistics	Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)
Secondary	PK parameter of oxaliplatin - Cmax (Cohorts 1A and 1B)	To be summarized using descriptive statistics	Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)
Secondary	PK parameter of oxaliplatin - Tmax (Cohorts 1A and 1B)	To be summarized using descriptive statistics	Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)
Secondary	Confirmed objective response rate (cORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per investigator assessment (INV) (Cohort 2A)	cORR is defined as the proportion of participants with confirmed complete response (CR) or partial response (PR)	Up to approximately 2.5 years
Secondary	Duration of response (DOR) according to RECIST v1.1 per INV (Cohorts 1C, 1E, 1F, 1G, and 2A)	DOR is defined as the time from first documentation of objective response of confirmed CR or confirmed PR to the first documentation of disease progression or death from any cause, whichever occurs first.	Up to approximately 2.5 years
Secondary	Progression-free survival (PFS) according to RECIST v1.1 per INV (Cohorts 1C, 1E, 1F, 1G, and 2A)	PFS is defined as the time from the date of treatment initiation to the date of disease progression or death from any cause, which occurs first.	Up to approximately 2.5 years
Secondary	Overall survival (OS) (Cohort 1C, 1E, 1F, 1G, and 2A)	OS is defined as the time from treatment initiation to death due to any cause	Up to approximately 2.5 years
Secondary	Objective response rate (ORR) (Cohorts 1C, 1E, 1F, and 1G)	ORR is defined as the proportion of subjects with confirmed CR or PR, according to RECIST v1.1.	Up to approximately 2.5 years