XmAb®808 + Pembrolizumab for Advanced Cancers

No longer recruiting at 11 trial locations

Overseen By Michael Chiarella

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Xencor, Inc.

Must not be taking: Anticancer therapies

Disqualifiers: CNS involvement, Life-threatening immunotherapy event, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment combination for people with advanced solid tumors. Researchers seek to determine the safety and pharmacokinetics of combining XmAb808 (an experimental treatment) with pembrolizumab (an immunotherapy drug). The trial seeks participants whose cancer has progressed despite standard treatments. It is suitable for individuals with advanced cancers such as prostate, ovarian, or breast cancer, who are not currently undergoing other cancer treatments. 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 treatment.

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

Yes, you must stop taking any current anticancer therapies to join this trial.

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

Research has shown that pembrolizumab was safe in previous studies. Specifically, the KEYNOTE-001 study for advanced melanoma found it well-tolerated over five years. Although some patients experienced rare immune-related side effects, such as type 1 diabetes, these were uncommon.

XmAb808 is a new treatment still under investigation. This trial is among the first to test it in humans, so data remains limited. As this is an early study, researchers aim to understand the safety of XmAb808 when combined with pembrolizumab. The safety information from this phase will guide decisions on the optimal dose and schedule.

In summary, pembrolizumab has a history of safety, while XmAb808 is still undergoing safety testing in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of XmAb®808 and pembrolizumab for advanced cancers because this treatment approach offers a unique mechanism of action. Unlike standard treatments that typically target cancer cells directly, XmAb®808 is an engineered antibody that enhances the body's immune response by bridging T-cells and tumor cells, potentially leading to a more effective attack on cancer cells. When combined with pembrolizumab, a well-known checkpoint inhibitor that unleashes the immune system against tumors, this duo might offer a more powerful and targeted approach to fighting advanced cancers. This combination could potentially increase effectiveness and reduce side effects compared to traditional chemotherapy or single-agent immunotherapies.

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

Research has shown that pembrolizumab, a treatment that aids the immune system, effectively treats several advanced cancers by enabling the body to attack cancer cells. Studies have found that pembrolizumab can slow disease progression and extend survival in some patients with certain cancers. XmAb®808, a newer drug, is designed to enhance the body's response against tumors. Although limited data exists on XmAb®808's effectiveness, this trial tests it in combination with pembrolizumab, as it might improve treatment by better targeting cancer cells. Early results suggest this combination could potentially benefit patients with advanced solid tumors. ^{1 4 5 6 7}

Who Is on the Research Team?

Mira Kistler, MD

Principal Investigator

Xencor, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced cancers (like prostate, ovarian, lung, and more) that have worsened despite standard treatments. Participants must be in relatively good physical condition with a life expectancy over 3 months. They shouldn't have had severe reactions to immunotherapy before or be on other cancer treatments.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer is advanced, has spread, and didn't respond to standard treatments.

My cancer is advanced, resistant to hormone therapy, and I haven't had PD1 therapy.

Exclusion Criteria

My brain cancer is stable after treatment.

I have never been treated with experimental drugs targeting CD28.

You had a very serious health problem in the past caused by a previous immunotherapy treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive multiple doses of XmAb808 in combination with pembrolizumab to evaluate safety and determine the recommended dose

7 weeks

Multiple visits (in-person)

Cohort Expansion

Participants receive the recommended dose of XmAb808 in combination with pembrolizumab to further evaluate safety and efficacy

Up to 5 years

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• XmAb®808

Trial Overview The study tests XmAb®808 combined with pembrolizumab (Keytruda®), both given through IV. It aims to find the safest and most effective dose of XmAb808 when used together with pembrolizumab in patients with specific types of advanced solid tumors.

How Is the Trial Designed?

Group I: Dose Escalation and Expansion XmAb®808 administered in combination with pembrolizumab Experimental Treatment 2 Interventions

XmAb®808 in combination with pembrolizumab

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?

Xencor, Inc.

Lead Sponsor

Trials

31

Recruited

2,500+

Published Research Related to This Trial

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]

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 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) 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]

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]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05585034

Study Details | NCT05585034 | Phase 1, First-in-human, ... The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of intravenous (IV) administration of XmAb808 in combination with ...

2. bcan.org bcan.org/clinicaltrials/xmab808-in-combination-with-pembrolizumab-in-advanced-solid-tumors/

XmAb®808 in Combination With Pembrolizumab ... The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of intravenous (IV) administration of XmAb808 in combination with ...

3. withpower.com withpower.com/trial/phase-1-triple-negative-breast-neoplasms-10-2022-8e240

XmAb®808 + Pembrolizumab for Advanced Cancers The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of intravenous (IV) administration of XmAb808 in combination with ...

4. georgiacancerinfo.net georgiacancerinfo.net/clinical-trials/detail/5395

Phase 1, First-in-human, Dose-finding and Expansion ... Summary. The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of intravenous (IV) administration of XmAb808 in ...

5. xencor.com xencor.com/clinical-trials/

Clinical Trials The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of intravenous (IV) administration of XmAb808 in combination with ...

6. investors.xencor.com investors.xencor.com/static-files/4c284ac3-3399-459b-a308-e442b9d5f984

A phase 1, first-in-human, open-label, dose-finding ... - Investors XmAb808 is anticipated to augment anti-tumor responses when used in combination with other immunotherapies, such as CD3-directed bispecific. T-cell engagers and ...

7. clinicaltrial.be clinicaltrial.be/en/details/13989?active_not_recruiting=1&completed=0&enrolling_by_invitation=1&only_active=0&only_eligible=0&only_recruiting=0&per_page=20

Phase 1, First-in-human, Dose-finding and Expansion ... ... Safety, Tolerability, Pharmacokinetics, and Activity of XmAb®808 in Combination With Pembrolizumab in Selected Advanced Solid Tumors.