Tucatinib + Trastuzumab + Chemotherapy for Gastrointestinal Cancer

Not currently recruiting at 54 trial locations

Overseen By Seagen Trial Information Support

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Must not be taking: Anti-HER2, Anti-PD-1

Disqualifiers: Hepatitis B, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 14

Duration: Up to approximately 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of drugs, including tucatinib (a targeted therapy) and trastuzumab (a monoclonal antibody therapy), to determine their safety in treating HER2-positive gastrointestinal cancers. Researchers aim to assess the combination's effectiveness and potential side effects. Individuals with HER2-positive cancer in the gut, stomach, intestines, or gallbladder, who qualify for certain chemotherapy regimens, might be suitable candidates. The trial involves different groups receiving various drug combinations to identify the best approach. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study center to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies have generally found tucatinib to be well-tolerated when used with trastuzumab and other cancer drugs. However, some side effects have occurred. When combined with trastuzumab and FOLFOX, serious side effects appeared in about 22% of patients, including intestinal blockage and urinary infections. For those taking tucatinib with trastuzumab and CAPOX, diarrhea was common, affecting 81% of patients, though only 0.5% experienced severe cases. Detailed safety data for tucatinib with pembrolizumab is not yet available, but the FDA has approved tucatinib and trastuzumab together for other cancers, indicating some level of safety. This is a Phase 2 trial, meaning the treatment has shown an acceptable safety profile in earlier research, but more data is needed to fully understand its safety in people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of tucatinib, trastuzumab, and chemotherapy for gastrointestinal cancer because it offers a novel approach by specifically targeting the HER2 protein, which plays a role in the growth of some cancer cells. Unlike standard treatments that might not specifically target HER2, tucatinib is a small-molecule inhibitor that works in tandem with trastuzumab, a monoclonal antibody, to more precisely attack cancer cells. Additionally, the integration of pembrolizumab, an immunotherapy drug, aims to enhance the body’s immune response against cancer, offering a potential boost in treatment efficacy. By combining these targeted therapies with established chemotherapy regimens, researchers hope to improve outcomes for patients with HER2-positive gastrointestinal cancers.

What evidence suggests that this trial's treatments could be effective for gastrointestinal cancer?

This trial will evaluate the effectiveness of different combinations of tucatinib, trastuzumab, and chemotherapy drugs like FOLFOX or CAPOX for treating HER2-positive gastrointestinal cancers. Studies have shown that combining tucatinib with trastuzumab and chemotherapy effectively treats HER2-positive cancers, leading to better survival rates compared to a placebo in similar cancer types. Tucatinib specifically targets the HER2 protein, helping to slow or stop cancer cell growth. Some arms of this trial will also include pembrolizumab, a drug that boosts the immune system to fight cancer. Research indicates that combining pembrolizumab with other treatments has improved survival rates in other HER2-positive cancers. These findings strongly support testing these combinations in this trial. ^{6 7 8 9 10}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for adults with HER2+ gastrointestinal cancers, including stomach and colorectal cancer, who can receive oxaliplatin-based chemotherapy. They must have a performance status that allows daily activities with minimal assistance. People cannot join if they've had severe immune-related side effects from certain cancer treatments or are known to be positive for Hepatitis B or C.

Inclusion Criteria

I have been diagnosed with cholangiocarcinoma.

My cancer is inoperable or has spread, and it's one of the specified types.

My cancer is one of the following: colorectal, stomach, esophageal, bile duct, or gallbladder.

Exclusion Criteria

I have previously received anti-HER2 therapies.

Known to be positive for Hepatitis B or C

I stopped a specific cancer treatment due to severe side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tucatinib in combination with trastuzumab and other anti-cancer drugs in cycles

Up to approximately 12 months

Cycles of 14, 21, or 42 days depending on cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 2.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Fluorouracil
• Leucovorin
• Pembrolizumab
• Trastuzumab
• Tucatinib

Trial Overview The study tests the safety and effectiveness of tucatinib combined with trastuzumab and other anti-cancer drugs like pembrolizumab, FOLFOX (a regimen including fluorouracil, leucovorin, and oxaliplatin), and CAPOX (capecitabine plus oxaliplatin). It aims to see how well these combinations work against various types of gastrointestinal cancers.

How Is the Trial Designed?

Group I: Cohort 2B Experimental Treatment 5 Interventions

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

Group II: Cohort 2A Experimental Treatment 7 Interventions

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.

Group III: Cohort 1G Experimental Treatment 3 Interventions

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

Group IV: Cohort 1F Experimental Treatment 5 Interventions

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

Group V: Cohort 1E Experimental Treatment 6 Interventions

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

Group VI: Cohort 1D Experimental Treatment 5 Interventions

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

Group VII: Cohort 1C Experimental Treatment 4 Interventions

Tucatinib + trastuzumab + CAPOX given in 21-day cycles

Group VIII: Cohort 1B Experimental Treatment 5 Interventions

Tucatinib + trastuzumab + FOLFOX given in 14-day cycles

Group IX: Cohort 1A Experimental Treatment 5 Interventions

Tucatinib + trastuzumab + FOLFOX given in 14-day cycles

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

Seagen, a wholly owned subsidiary of Pfizer

Lead Sponsor

Trials

20

Recruited

4,900+

Seagen Inc.

Lead Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Published Research Related to This Trial

In Korea, patients with advanced gastric cancer who undergo D2 resection benefit from postoperative adjuvant chemotherapy with S-1 or capecitabine plus oxaliplatin, indicating a potential effective treatment strategy in this population.

Trastuzumab is now part of the standard chemotherapy for gastric cancers that overexpress the HER2 protein, highlighting the importance of targeted therapies in improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for advanced gastric cancer: review and update of current practices. Park, SC., Chun, HJ.[2023]

Capecitabine, an oral medication, showed at least equivalent efficacy to intravenous 5-FU plus leucovorin in treating metastatic colorectal cancer, with an overall response rate of 18.9% compared to 15.0% for 5-FU/LV among 602 patients.

Capecitabine had a more favorable safety profile, resulting in significantly lower rates of stomatitis and neutropenia, while being associated with a higher incidence of hand-foot syndrome, making it a convenient and effective alternative to traditional IV treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. Van Cutsem, E., Twelves, C., Cassidy, J., et al.[2022]

Pemetrexed shows promising efficacy in treating gastrointestinal tumors, with a 15-17% response rate in metastatic colorectal cancer and a 6% response rate in advanced pancreatic cancer, comparable to standard treatments like gemcitabine.

The drug has a generally mild side effect profile, especially when combined with folate supplementation and dexamethasone, indicating potential for further studies to explore its role in combination therapies for colorectal, pancreatic, and gastric cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in patients with gastrointestinal carcinoma. de Gramont, A., Kindler, HL.[2019]

In a study of 34 patients with HER2-positive advanced gastric cancer, the combination of trsatuzumab (Herceptin) with the FOLFIRI regimen resulted in a significantly higher overall response rate of 58.8% compared to 35.3% for the FOLFIRI regimen alone.

The combination treatment also demonstrated a high disease control rate of 88.2%, indicating its efficacy, while the most common side effects were manageable grade I/II adverse events like diarrhea and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of trsatuzumab (Herceptin) combined with FOLFIRI regimen in the treatment of HER2-positive advanced gastric cancer]. Sun, J., Pan, SY., Chen, QQ., et al.[2015]

No chemotherapy regimen has shown a survival benefit greater than 5-fluorouracil alone for advanced gastric cancer, but recent trials have introduced new agents and strategies that may improve outcomes.

Trastuzumab has demonstrated a survival benefit for patients with Her-2 positive gastric cancer, indicating a shift towards personalized treatment approaches using molecular targeted therapies in advanced gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives for personalization in chemotherapy of advanced gastric cancer. Boku, N.[2015]

Recent trials indicate that oral fluoropyrimidine agents like capecitabine (Xeloda) and UFT/leucovorin are as effective as standard intravenous 5-FU in treating advanced colorectal cancer, showing similar response rates and survival outcomes.

These oral agents also have the added benefit of reducing side effects such as neutropenia and stomatitis, making them a promising option for patients undergoing treatment for colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of oral chemotherapy in colorectal cancer. Donehower, RC.[2015]

In the KEYNOTE-811 study, combining pembrolizumab with trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma significantly reduced tumor size and improved the objective response rate, indicating enhanced efficacy of this treatment regimen.

The study highlights that this combination therapy not only induces complete responses in some patients but also represents a promising advancement in the treatment of unresectable or metastatic HER2-positive cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Janjigian, YY., Kawazoe, A., Yañez, P., et al.[2022]

5-fluorouracil (5-FU) remains a key chemotherapy drug for colorectal cancer, but its oral form was previously abandoned due to inconsistent absorption; however, Xeloda (capecitabine) offers a solution by being an orally administered drug that is selectively activated in tumors, leading to higher local concentrations of 5-FU.

In phase II clinical trials for colorectal cancer, Xeloda demonstrated response rates of 21-24% and a median time to disease progression of 127-230 days, indicating its efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoropyrimidines: a critical evaluation. Brito, RA., Medgyesy, D., Zukowski, TH., et al.[2017]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1914609

Tucatinib, Trastuzumab, and Capecitabine for HER2 ... Adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo.

2. onclive.com onclive.com/view/real-world-data-support-tucatinib-based-treatment-in-her2-metastatic-breast-cancer

Real-World Data Support Tucatinib-Based Treatment in ... Tucatinib-based treatments showed effectiveness in HER2-positive metastatic breast cancer, including brain metastases and post-T-DXd treatment ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11922774/

Tucatinib and trastuzumab in HER2-mutated metastatic breast ... These data support further investigation of HER2-targeted therapies in this patient population. ClinicalTrials.gov registration: NCT04579380.

4. tukysahcp.com tukysahcp.com/mbc/efficacy

TUKYSA® (tucatinib) 2L+HER2+ MBC Efficacy - Safety Info View efficacy data for the TUKYSA® (tucatinib) Rx regimen, in combination with trastuzumab plus capecitabine. Read full indication and important safety ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04430738

Study Details | NCT04430738 | Tucatinib Plus ... This trial studies tucatinib to find out if it is safe when given with trastuzumab and other anti-cancer drugs (pembrolizumab, FOLFOX, and CAPOX).

6. tukysahcp.com tukysahcp.com/mbc

TUKYSA® (tucatinib) , HER2+ MBC - Safety Info In HER2CLIMB, when TUKYSA was given in combination with trastuzumab and capecitabine, 81% of patients who received TUKYSA experienced diarrhea, including 0.5% ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/213411s004lbl.pdf

TUKYSA® (tucatinib) tablets, for oral use - accessdata.fda.gov The safety of TUKYSA in combination with trastuzumab or a non-US approved trastuzumab product was evaluated in 86 patients enrolled in MOUNTAINEER with ...

8. tukysahcp.com tukysahcp.com/mbc/safety

Safety Info for TUKYSA® (tucatinib) in 2L+ HER2+ MBC The Prescribing Information for TUKYSA contains warnings and precautions for diarrhea, hepatotoxicity, and embryo-fetal toxicity, some of which may be severe ...

9. tukysa.com tukysa.com/mbc/what-is-tukysa

About TUKYSA® (tucatinib) for HER2+ MBC - Safety Info TUKYSA is taken with trastuzumab, they work together to offer another chance to slow the progression of cancer and may help you live longer.

10. clinicaltrials.gov clinicaltrials.gov/study/NCT02025192

NCT02025192 | A Study of Tucatinib (ONT-380) Combined ... This is a study of tucatinib (ONT-380) given in combination with capecitabine alone, trastuzumab alone and with both capecitabine and trastuzumab in patients ...