XB010 + Pembrolizumab for Cancer

Recruiting at 7 trial locations

Overseen By Backup or International

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Exelixis

Disqualifiers: Diabetes, Hypertension, Bipolar, others

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

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

Compensation: Varies

Number of Visits: 6

396 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a FIH study is to evaluate the safety, tolerability, PK, immunogenicity, and preliminary antitumor activity of XB010 as a single agent and in combination with pembrolizumab in subjects with locally advanced or metastatic solid tumors for whom alternative therapies do not exist or available therapies are intolerable or no longer effective.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug pembrolizumab in treating cancer?

Pembrolizumab has been shown to improve survival rates in patients with certain types of lung cancer and melanoma, as it helps the immune system better recognize and attack cancer cells. It has been approved for use in these cancers after demonstrating significant benefits in clinical trials. ^{1 2 3 4 5}

What safety information is available for Pembrolizumab (Keytruda) in humans?

Pembrolizumab (Keytruda) has been associated with some immune-related side effects, including a rare risk of developing type 1 diabetes in 0.2% of cases and pneumonitis (lung inflammation) in 1%-5% of patients. Common side effects include fatigue, cough, nausea, rash, and diarrhea. ^{1 2 5 6 7}

What makes the drug XB010 + Pembrolizumab unique for cancer treatment?

The combination of XB010 and Pembrolizumab is unique because Pembrolizumab is a PD-1 inhibitor that helps the immune system attack cancer cells, and it has shown effectiveness in various cancers like melanoma and lung cancer. This combination may offer a novel approach by potentially enhancing the immune response against cancer compared to using Pembrolizumab alone. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for individuals with advanced or metastatic solid tumors when other treatments aren't available, are intolerable, or have stopped working. Specific eligibility details are not provided but typically include factors like age, health status, and type of tumor.

Inclusion Criteria

I am 18 years old or older.

I am fully active or can carry out light work.

My organs and bone marrow are working well.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation

Determine the maximum tolerated dose (MTD) and/or recommended dosage(s) for expansion (RDE[s]) of XB010 as a single agent and in combination with pembrolizumab

18 months

Every 3 weeks

Cohort-Expansion

Explore the clinical activity and further characterize the safety and tolerability of XB010 as monotherapy in multiple tumor-specific cohorts

24 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Pembrolizumab
• XB010

Trial Overview The study investigates XB010 alone and combined with pembrolizumab to assess safety, tolerability, how the body processes it (PK), immune response (immunogenicity), and initial effectiveness against tumors in subjects whose cancer has spread.

Participant Groups

Group I: XB010 Single-Agent Dose Expansion Cohorts Experimental Treatment 1 Intervention

XB010 will be administered at the recommended dose for expansion (RDE) every 3 weeks in the following tumor-specific cohorts: non-small cell lung cancer (NSCLC), hormone-receptor-positive breast cancer (HR+BC), head and neck squamous cell cancer (HNSCC), esophageal squamous cell cancer (ESCC), endometrial cancer (EC) and triple-negative breast cancer (TNBC)

Group II: XB010 Single-Agent Dose Escalation Cohorts Experimental Treatment 1 Intervention

XB010 will be administered at escalating dose levels every 3 weeks in cohorts of 3-12 subjects

Group III: XB010 + Pembrolizumab Dose Escalation Cohorts Experimental Treatment 2 Interventions

XB010+Pembrolizumab will be administered at escalating dose levels every 3 weeks in cohorts of 3-12 subjects

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Exelixis

Lead Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

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, 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) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

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]

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. England pubmed.ncbi.nlm.nih.gov

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

3. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. [2021]

4. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

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

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

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

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

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

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