Tucatinib + Trastuzumab + Chemotherapy for Gastrointestinal Cancer

Recruiting at 48 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

41 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

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.

What data supports the effectiveness of the drug combination Tucatinib + Trastuzumab + Chemotherapy for gastrointestinal cancer?

The KEYNOTE-811 trial showed that adding pembrolizumab to trastuzumab and chemotherapy significantly improved response rates in HER2-positive gastric cancer, suggesting potential benefits of combining similar drugs like tucatinib with trastuzumab and chemotherapy for gastrointestinal cancers. ^{1 2 3 4 5}

Is the combination of Tucatinib, Trastuzumab, and Chemotherapy safe for humans?

Research on capecitabine (Xeloda) and 5-fluorouracil (5-FU), which are part of the chemotherapy regimen, shows they have been used safely in treating colorectal cancer, with some side effects like neutropenia (low white blood cell count) and stomatitis (mouth sores) being less common with oral capecitabine compared to intravenous 5-FU. Safety can vary based on individual genetic factors, and ongoing research aims to improve safety by tailoring treatments to genetic profiles. ^{6 7 8 9 10}

What makes the drug combination of Tucatinib, Trastuzumab, and Chemotherapy unique for gastrointestinal cancer?

This drug combination is unique because it includes tucatinib, a targeted therapy that, along with trastuzumab, specifically targets HER2-positive cancer cells, which are a subset of gastric cancers. This approach is part of a new era of personalized medicine, aiming to improve outcomes by using molecularly targeted agents in combination with traditional chemotherapy. ^{1 2 5 11 12}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pemetrexed in patients with gastrointestinal carcinoma. [2019]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Chemotherapy for advanced gastric cancer: review and update of current practices. [2023]

3. England pubmed.ncbi.nlm.nih.gov

The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

The role of pemetrexed in the treatment of gastrointestinal malignancy. [2019]

5. China pubmed.ncbi.nlm.nih.gov

[Efficacy of trsatuzumab (Herceptin) combined with FOLFIRI regimen in the treatment of HER2-positive advanced gastric cancer]. [2015]

6. United States 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin. [2022]

8. Scotland pubmed.ncbi.nlm.nih.gov

Host genetic profiling to increase drug safety in colorectal cancer from discovery to implementation. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Fluoropyrimidines: a critical evaluation. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Role of oral chemotherapy in colorectal cancer. [2015]

11. United States pubmed.ncbi.nlm.nih.gov

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

12. France pubmed.ncbi.nlm.nih.gov

New developments and standard of care in the management of advanced gastric cancer. [2023]