XmAb®808 + Pembrolizumab for Advanced Cancers

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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of intravenous (IV) administration of XmAb808 in combination with pembrolizumab in subjects with selected advanced solid tumors and to identify the minimum safe and biologically effective/recommended dose (RD) and schedule for XmAb808.

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.

What data supports the idea that XmAb®808 + Pembrolizumab for Advanced Cancers is an effective drug?

The available research shows that Pembrolizumab, a part of the XmAb®808 + Pembrolizumab combination, has been effective in treating various advanced cancers. For instance, it has been approved for treating advanced melanoma and non-small cell lung cancer, showing significant improvements in survival compared to chemotherapy. In lung cancer, patients treated with Pembrolizumab had better survival rates than those receiving standard chemotherapy. This suggests that the combination with XmAb®808 could also be promising for advanced cancers. ^{1 2 3 4 5}

What safety data is available for XmAb®808 and Pembrolizumab in cancer treatment?

Safety data for Pembrolizumab (also known as KEYTRUDA or MK-3475) includes findings from various studies. In a phase II trial for non-small cell lung cancer, interim safety analysis was conducted. Pembrolizumab received FDA approval for metastatic melanoma based on a phase 1 trial, with common adverse reactions like fatigue, cough, and immune-mediated reactions such as pneumonitis and thyroid disorders. In the KEYNOTE-001 study for advanced melanoma, Pembrolizumab showed robust safety over five years. Rare immune-related adverse events include type 1 diabetes mellitus and pneumonitis, occurring in a small percentage of patients. No specific safety data for XmAb®808 is mentioned in the provided research. ^{5 6 7 8 9}

Is the drug Pembrolizumab, also known as Keytruda, a promising treatment for advanced cancers?

Yes, Pembrolizumab (Keytruda) is a promising drug for advanced cancers. It has been approved for treating various types of cancer, including esophageal, gastroesophageal, non-small cell lung cancer, and endometrial carcinoma. It works by helping the immune system fight cancer cells, and has shown positive results in clinical trials. ^{1 4 5 9 10}

Research Team

Mira Kistler, MD

Principal Investigator

Xencor, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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, 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]

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, 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 (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. England pubmed.ncbi.nlm.nih.gov

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

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

Pembrolizumab: first global approval. [2021]

3. 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]

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

5. 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]

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]

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

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]

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

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

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

New Approved Use for Keytruda. [2022]