Telatinib + Keytruda for Stomach and Liver Cancer

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining telatinib and Keytruda (an immunotherapy drug) for individuals with certain advanced types of stomach or liver cancer. The researchers seek to determine if this treatment can prevent the cancer from worsening. It offers an opportunity for those with stomach cancer unresponsive to at least two treatments or liver cancer unresponsive to at least one treatment. Participants should have measurable cancer that has not been treated with radiation. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that the combination of Telatinib and Keytruda has been studied for safety in patients with advanced stomach and liver cancers. Previous studies have found that Keytruda, a commonly used immunotherapy, is generally well-tolerated by patients with these cancers. Common side effects include tiredness and nausea, which are usually manageable.

The safety of combining Telatinib with Keytruda remains under investigation. Specific data on this combination is limited, but the current trial phase suggests it is safe enough for testing in people. Earlier research did not identify any serious safety issues.

While complete information on side effects for this combination is not yet available, the trial phase suggests it is expected to be safe based on earlier findings. Participants in similar studies have shown that side effects are often mild to moderate. However, as with any treatment, careful monitoring during the trial will be important to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Telatinib combined with Keytruda for stomach and liver cancer because this treatment targets cancer in a unique way. Unlike traditional therapies that might focus on directly killing cancer cells, Telatinib is known to block certain proteins that help tumors grow new blood vessels, effectively cutting off their blood supply. Keytruda, on the other hand, unleashes the immune system to attack cancer cells by blocking a pathway that tumors use to hide. Together, these drugs offer a one-two punch: starving the tumor while boosting the body's natural defenses, potentially improving outcomes for patients in ways current treatments like chemotherapy or single-agent immunotherapies might not.

What evidence suggests that telatinib + Keytruda could be effective for stomach and liver cancer?

Research has shown that combining Keytruda with chemotherapy improves outcomes in treating various cancers, including stomach cancer. This combination has extended patients' lives without cancer progression. In this trial, researchers aim to evaluate how telatinib works with Keytruda, as it may influence proteins related to advanced stomach and liver cancer. Although limited data exists on the combined use of telatinib and Keytruda, Keytruda alone has proven effective in improving survival rates when used with other treatments. ^{1 3 5 6 7}

Who Is on the Research Team?

Andrew Hendifar, MD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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]

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]

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) 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]

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 (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) 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04798781

Safety and Efficacy of Telatinib in Combination With ... This is a phase II, single arm, open-label study of two parallel cohorts (advanced stomach and gastroesophageal junction cancer and hepatocellular ...

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/81/NCT04798781/Prot_SAP_000.pdf

IIT2020-11-Hendifar-TELAT It is of interest to determine if telatinib in combination with Keytruda has an impact on inflammatory cytokines associated with advanced gastric cancer or HCC.

3. clin.larvol.com clin.larvol.com/trial-detail/NCT04798781

Safety and Efficacy of Telatinib in Combination With ... Safety and Efficacy of Telatinib in Combination With Keytruda in Subjects With Advanced Stomach and Gastroesophageal Junction Cancers or Hepatocellular ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9892960/

KEYNOTE-859: a Phase III study of pembrolizumab plus ... Combining pembrolizumab with chemotherapy has demonstrated efficacy and manageable safety in multiple tumor types, including gastric cancer [13,15–17]. Based on ...

5. merck.com merck.com/news/mercks-keytruda-pembrolizumab-plus-chemotherapy-significantly-improved-overall-survival-versus-chemotherapy-alone-in-patients-with-her2-negative-gastric-or-gastroesophageal-junction/

Merck's KEYTRUDA® (pembrolizumab) Plus ... In KEYNOTE-859, KEYTRUDA combined with chemotherapy also showed statistically significant improvements in progression-free survival and objective response ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04798781/safety-and-efficacy-of-telatinib-in-combination-with-keytruda-in-subjects-with-advanced-stomach-and-gastroesophageal-junction-cancers-or-hepatocellular-carcinoma

Safety and Efficacy of Telatinib in Combination With ... Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1 or 2. Adequate bone marrow, liver, and renal function. Negative urine or ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11622097/

Pembrolizumab in patients with gastric cancer and liver ... In this editorial, we explore the impact of immunotherapy and its safety in patients with advanced gastric cancer (GC) and liver involvement.