Telatinib + Keytruda for Stomach and Liver Cancer

Recruiting at 7 trial locations

Overseen By Abrahm Levi, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Andrew Hendifar, MD

Must be taking: Keytruda

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Brain metastasis, Cardiac disease, Hypertension, Infection, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

16 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of two drugs, telatinib and Keytruda, in patients with advanced stomach, gastroesophageal junction cancer, and liver cancer. Telatinib aims to stop cancer growth, while Keytruda helps the immune system fight the cancer. The goal is to see if this combination can help patients live longer without their cancer worsening.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop these at least 7 days before starting the trial treatment.

What data supports the effectiveness of the drug Keytruda (pembrolizumab) for stomach and liver cancer?

Pembrolizumab (Keytruda) has been shown to be effective in treating esophageal or gastroesophageal cancer and has been used successfully in patients with recurrent gastric cancer, suggesting it may also be beneficial for stomach cancer. ^{1 2 3 4 5}

Is the combination of Telatinib and Keytruda safe for humans?

Keytruda (Pembrolizumab) has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, nausea, and immune-related issues such as pneumonitis (lung inflammation) and type 1 diabetes in rare cases. There is no specific safety data available for the combination of Telatinib and Keytruda, but Keytruda's safety profile is well-documented in other conditions. ^{1 6 7 8 9}

What makes the drug combination of Telatinib and Keytruda unique for treating stomach and liver cancer?

The combination of Telatinib and Keytruda is unique because it pairs an immune checkpoint inhibitor (Keytruda) with another drug (Telatinib) to potentially enhance the immune system's ability to fight cancer, offering a novel approach compared to traditional chemotherapy. ^{1 2 5 8 10}

Research Team

Andrew Hendifar, MD

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

Adults with advanced stomach, gastroesophageal junction cancers or hepatocellular carcinoma that have progressed after prior treatments and are PD-L1-positive. They must be able to swallow tablets, not have uncontrolled infections or certain other health conditions, and agree to use contraception.

Inclusion Criteria

Able to swallow tablets and agree to take the prescribed tablets twice daily.

Diagnosis: Histologically confirmed gastric/esophagealgastric adenocarcinoma, recurrent, locally advanced or metastatic, PD-L1-positive disease (CPS ≥1), progressed on at least two prior lines of therapy and/or discontinued second line therapy for intolerance, indicated for Keytruda therapy. OR: Hepatocellular carcinoma with diagnosis confirmed by histologic or cytologic analysis or clinical features according to the American Association for the Study of Liver Diseases criteria for patients with cirrhosis, unresectable disease not amenable to locoregional therapy with disease progression after at least one prior line of systemic therapy or discontinued first line therapy for intolerance.

At least 1 measurable metastatic lesion that has not been irradiated. The lesion will be measured according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), and be documented by radiological evaluation within 28 days prior to registration. For subjects with locally advanced disease: at least one measurable lesion that has not been irradiated, documented by radiological evaluation within 28 days prior to registration.

Exclusion Criteria

Uncontrolled hypertension

Severe hemorrhage/bleeding event within 28 days prior to the first dose of study treatment

Major surgery, open biopsy, or significant traumatic injury within 42 days prior to the first dose of study treatment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive telatinib in combination with Keytruda

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Treatment Details

Interventions

• Keytruda
• Telatinib

Trial Overview The trial is testing the combination of Telatinib and Keytruda in patients with specific advanced cancers. It's an open-label study focusing on how these drugs affect the time a patient lives without their disease getting worse.

Participant Groups

Group I: telatinib + Keytruda Experimental Treatment 2 Interventions

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

Approved in United States as Keytruda for:

• Melanoma
• Non-small cell lung cancer
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Merkel cell carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma
• Esophageal cancer
• Triple-negative breast cancer

Approved in European Union as Keytruda for:

• Melanoma
• Non-small cell lung cancer
• Urothelial carcinoma
• Head and neck squamous cell carcinoma
• Hepatocellular carcinoma
• Renal cell carcinoma
• Colorectal cancer
• Gastric cancer
• Cervical cancer
• Endometrial carcinoma
• Esophageal cancer
• Triple-negative breast cancer

Approved in Japan as Keytruda for:

• Melanoma
• Non-small cell lung cancer
• Urothelial carcinoma
• Head and neck squamous cell carcinoma
• Hepatocellular carcinoma
• Renal cell carcinoma
• Colorectal cancer
• Gastric cancer

Approved in Canada as Keytruda for:

• Melanoma
• Non-small cell lung cancer
• Urothelial carcinoma
• Head and neck squamous cell carcinoma
• Hepatocellular carcinoma
• Renal cell carcinoma
• Colorectal cancer
• Gastric cancer
• Cervical cancer
• Endometrial carcinoma
• Esophageal cancer
• Triple-negative breast cancer

Who Is Running the Clinical Trial?

Andrew Hendifar, MD

Lead Sponsor

Trials

6

Recruited

130+

EOC Pharma

Industry Sponsor

Trials

1

Recruited

20+

EOC Pharma

Collaborator

Trials

1

Recruited

20+

Findings from Research

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

The study found that using 89Zr-trastuzumab PET and ctDNA monitoring can help identify early signs of treatment resistance in patients with HER2-positive metastatic esophagogastric cancer, potentially guiding treatment adjustments.

Patients with ERBB2 amplification showed improved progression-free survival (PFS), while those with alterations in MYC and CDKN2A/B had worse PFS, indicating that specific genetic markers can predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer. Maron, SB., Chatila, W., Walch, H., et al.[2023]

Pembrolizumab (KEYTRUDA®) has shown efficacy and safety in treating recurrent high microsatellite instability (MSI-high) gastric cancer, as demonstrated in the KEYNOTE-158 and 061 trials.

In a case study of an elderly patient with recurrent gastric cancer after surgery, pembrolizumab was successfully used as a second-line treatment, suggesting it can be a viable option for older patients in late-line chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-Term Elderly Survivor with Recurrent MSI-High Gastric Cancer Using Pembrolizumab as a Second-Line Chemotherapy]. Hamada, S., Komatsu, S., Nishiko, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

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

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021]

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

Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer. [2023]

5. Japan pubmed.ncbi.nlm.nih.gov

[Long-Term Elderly Survivor with Recurrent MSI-High Gastric Cancer Using Pembrolizumab as a Second-Line Chemotherapy]. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

New Approved Use for Keytruda. [2022]