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

Seagen

Status and phase

Active, not recruiting

Phase 2

Phase 1

Conditions

Colorectal Carcinoma

Cholangiocarcinoma

Esophageal Adenocarcinoma

Gallbladder Carcinoma

Gastric Adenocarcinoma

GEJ Adenocarcinoma

Treatments

Drug: oxaliplatin

Drug: trastuzumab

Drug: leucovorin

Drug: fluorouracil

Drug: tucatinib

Drug: pembrolizumab

Drug: capecitabine

Study type

Interventional

Funder types

Industry

Identifiers

NCT04430738

SGNTUC-024

Details and patient eligibility

About

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).

Enrollment

40 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

40 participants in 9 patient groups

Cohort 1A

Experimental group

Description:

Tucatinib + trastuzumab + FOLFOX given in 14-day cycles

Treatment:

Drug: fluorouracil

Drug: tucatinib

Drug: leucovorin

Drug: trastuzumab

Drug: oxaliplatin

Cohort 1B

Experimental group

Description:

Tucatinib + trastuzumab + FOLFOX given in 14-day cycles

Treatment:

Drug: fluorouracil

Drug: tucatinib

Drug: leucovorin

Drug: trastuzumab

Drug: oxaliplatin

Cohort 1C

Experimental group

Description:

Tucatinib + trastuzumab + CAPOX given in 21-day cycles

Treatment:

Drug: capecitabine

Drug: tucatinib

Drug: trastuzumab

Drug: oxaliplatin

Cohort 1D

Experimental group

Description:

Tucatinib + trastuzumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles and trastuzumab given every 21 days

Treatment:

Drug: fluorouracil

Drug: tucatinib

Drug: leucovorin

Drug: trastuzumab

Drug: oxaliplatin

Cohort 1E

Experimental group

Description:

Tucatinib + trastuzumab + pembrolizumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles, trastuzumab given in 21-day cycles, and pembrolizumab given in 42-day cycles

Treatment:

Drug: pembrolizumab

Drug: fluorouracil

Drug: tucatinib

Drug: leucovorin

Drug: trastuzumab

Drug: oxaliplatin

Cohort 1F

Experimental group

Description:

Tucatinib + trastuzumab + pembrolizumab + CAPOX. Tucatinib, trastuzumab, and CAPOX given in 21-day cycles and pembrolizumab given in 42-day cycles.

Treatment:

Drug: capecitabine

Drug: pembrolizumab

Drug: tucatinib

Drug: trastuzumab

Drug: oxaliplatin

Cohort 1G

Experimental group

Description:

Tucatinib + trastuzumab + pembrolizumab. Tucatinib and trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles.

Treatment:

Drug: pembrolizumab

Drug: tucatinib

Drug: trastuzumab

Cohort 2A

Experimental group

Description:

Tucatinib + trastuzumab + pembrolizumab + (FOLFOX or CAPOX). Either (1) tucatinib and FOLFOX given in 14-day cycles or (2) tucatinib and CAPOX given in 21-day cycles. Trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles.

Treatment:

Drug: capecitabine

Drug: pembrolizumab

Drug: fluorouracil

Drug: tucatinib

Drug: leucovorin

Drug: trastuzumab

Drug: oxaliplatin

Cohort 2B

Experimental group

Description:

Tucatinib + trastuzumab + FOLFOX given in 14-day cycles.