XB010 + Pembrolizumab for Cancer

(DELTA-101 Trial)

Recruiting at 18 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the new drug, XB010, is safe and effective alone or with pembrolizumab (an immunotherapy drug) for treating advanced cancers. It targets solid tumors that cannot be surgically removed or have metastasized. The trial includes different groups to assess the drug's effectiveness for specific cancers, such as lung, breast, and head and neck cancers. It suits individuals with confirmed advanced or recurrent solid tumors who have no other treatment options. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

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

Research shows that pembrolizumab is generally well-tolerated. The FDA has already approved it for other types of cancer, indicating its safety is well understood. Common side effects include fatigue, skin rash, and diarrhea.

For XB010, less information is available because it is a new drug. Early lab research showed it could effectively fight tumors. However, since this is the first human trial for XB010, its safety is still under evaluation. Possible side effects might include nausea or fatigue, but more details will emerge as more participants join the trials.

The combination of XB010 with pembrolizumab remains under study, and researchers are gathering more safety information. Participants will be closely monitored to identify any new side effects from this combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about XB010, both as a single agent and in combination with Pembrolizumab, because it targets cancer cells in a unique way. Unlike traditional treatments that might focus solely on blocking cancer cell growth, XB010 is being explored for its ability to enhance the immune system's natural ability to fight cancer. This new mechanism of action could potentially improve outcomes for patients with challenging cancers like non-small cell lung cancer and triple-negative breast cancer. By combining XB010 with Pembrolizumab, which is already known to boost the immune response against cancer, there is hope for a more effective treatment strategy.

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

Research has shown that XB010, a new treatment, holds promise in fighting tumors based on early studies. It successfully stopped cancer cell growth in lab tests and reduced tumor size in animals. In this trial, some participants will receive XB010 as a single agent to test its effects on different cancers, such as certain types of lung and breast cancer.

Other participants will receive a combination of XB010 and pembrolizumab. Early results suggest that this combination might enhance the immune system's ability to fight cancer. Pembrolizumab is already a well-known treatment that helps the body defend against tumors. Together, these treatments could offer a new option for people with advanced cancers that haven't responded to other treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

Study Director

Principal Investigator

Exelixis

Are You a Good Fit for This Trial?

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

Capable of understanding and complying with the protocol requirements and must have signed the informed consent document

I am fully active or can carry out light work.

My organs and bone marrow are working well.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06545331

Study of XB010 in Subjects With Solid Tumors

The Cohort Expansion stage will enroll subjects with multiple tumor types (non-small cell lung cancer, hormone-receptor-positive breast cancer, head and neck ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40836888/

Preclinical characterization of XB010: a novel antibody ...

XB010 is a novel anti-5T4 ADC that exhibits potent anti-tumor activity, inhibiting cancer cell growth in vitro and tumor growth in various in ...

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allclinicaltrials.com

allclinicaltrials.com/study/NCT06545331

Study of XB010 in Subjects With Solid Tumors

This is a FIH study is to evaluate the safety, tolerability, PK, immunogenicity, and preliminary antitumor activity of XB010 as a single ...

4.

cancer.gov

cancer.gov/clinicaltrials/NCI-2024-09409

Study of XB010 in Subjects With Solid Tumors - NCI

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 ...

5.

clinicaltrial.be

clinicaltrial.be/en/details/445426?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Study of XB010 in Subjects With Solid Tumors

The Cohort Expansion stage will enroll subjects with multiple tumor types (non-small cell lung cancer, hormone-receptor-positive breast cancer, head and neck ...