A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors

(DUET-4 Trial)

Recruiting at 27 trial locations

Overseen By Benjamin Thompson, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Xencor, Inc.

Must not be taking: Antibiotics, CTLA4 antibodies

Disqualifiers: Autoimmune disease, HIV, Hepatitis, 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

Duration: 8 weeks

78 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that certain treatments, like systemic antineoplastic therapy and some antibodies, should not be taken close to the start of the study. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Pembrolizumab (Keytruda) in treating cancer?

Pembrolizumab has been shown to be effective in treating certain types of cancer, such as non-small cell lung cancer and melanoma. It works by helping the immune system attack cancer cells, and studies have shown it can improve survival rates compared to traditional chemotherapy. ^{1 2 3 4 5}

What safety data exists 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. Common side effects include fatigue, cough, nausea, itching, rash, decreased appetite, constipation, joint pain, and diarrhea. Serious immune-related side effects can include lung inflammation, liver inflammation, and thyroid disorders. ^{1 2 3 6 7}

What is the purpose of this trial?

This trial is testing a new drug called XmAb22841 alone and with another drug, pembrolizumab, in patients with advanced solid tumors. The goal is to find the safest dose and see how well these drugs work together. Both drugs aim to boost the immune system to better fight cancer. Pembrolizumab has been shown to be an effective and safe therapeutic option in various cancers, including melanoma, prostate cancer, and endometrial cancer.

Research Team

Benjamin Thompson, MD, PhD

Principal Investigator

Xencor, Inc.

Eligibility Criteria

Inclusion Criteria

You have a confirmed advanced or metastatic solid tumor that has not responded to all available treatments that are known to help, or you cannot tolerate treatment, or you do not want to have standard treatment. You have one of these eligible types of tumors: melanoma, non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, hepatocellular carcinoma, gastric adenocarcinoma, cervical carcinoma, triple-negative breast carcinoma, epithelial ovarian cancer, nasopharyngeal carcinoma, squamous cell anal carcinoma, squamous cell penile carcinoma, or squamous cell vulvar carcinoma.

You have been diagnosed with advanced or metastatic cancer in one of the following areas: skin, cervix, pancreas, breast, liver, bladder, head and neck, nasopharynx, kidney, colon, uterus, lung, stomach, prostate, or ovaries.

PART A (Dose Escalation Cohorts): All subjects' cancer must have progressed after treatment with all available therapies that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment. All subjects must have adequate archival tumor, or give consent to a fresh tumor biopsy. Subjects have an ECOG performance status of 0-1.

Exclusion Criteria

You have taken medication in the past that stimulates or suppresses T-cells, such as anti-PD1, anti-PDL1, or anti-PDL2 agents, and had to stop taking it because of an immune-related adverse event.

You have recovered from any side effects of previous cancer treatment, except for immune-related side effects, to a level of Grade 2 or lower.

You have an autoimmune disease that is currently active, except for certain conditions such as vitiligo, type 1 diabetes, and manageable skin or joint conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive XmAb®22841 monotherapy or in combination with pembrolizumab in a multiple dose, ascending-dose escalation study

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pembrolizumab
• XmAb®22841

Participant Groups

Group I: Arm 2 Experimental Treatment 2 Interventions

Arm 2: Combination of XmAb®22841 and Pembrolizumab (Keytruda®)

Group II: Arm 1 Experimental Treatment 1 Intervention

Arm 1: XmAb®22841 Monotherapy

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+

ICON Clinical Research

Industry Sponsor

Trials

52

Recruited

15,100+

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 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, 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) 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 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

Pembrolizumab: first global approval. [2021]

5. 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]

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

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

7. England pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. [2022]