XmAb®22841 + Pembrolizumab for Cancer

(DUET-4 Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called XmAb22841, both alone and with pembrolizumab (KEYTRUDA), to assess their safety and effectiveness for individuals with certain advanced solid tumors. The goal is to determine the optimal dose and understand the treatment's effects on tumors. The study seeks participants whose cancer has worsened despite other treatments or who have refused or cannot tolerate standard treatments. Eligible participants may have cancers such as melanoma, cervical, pancreatic, or breast cancer, and these conditions affect their daily lives. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive it.

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.

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

Previous studies have tested the safety of XmAb22841 both alone and with pembrolizumab in patients with advanced solid tumors. Researchers assessed the safety and tolerability of XmAb22841 by monitoring any unwanted effects from the treatment.

When combined with pembrolizumab, a well-known and safe cancer treatment, the goal is to enhance effectiveness without adding significant risks. Pembrolizumab has a proven safety record in treating various cancers, including melanoma, prostate, and endometrial cancers.

As this trial is in its early stages, it primarily aims to determine the safest dose levels and understand any potential side effects. Early-phase trials closely monitor participants' reactions to ensure safety remains a priority. While specific data from the trial is not provided here, researchers are carefully studying the combination of these treatments to ensure safety for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about XmAb®22841 because it offers a novel approach to treating advanced solid tumors. Unlike traditional treatments that might target broader cancer cell markers, XmAb®22841 is designed to specifically modulate the immune checkpoint called CTLA-4, potentially boosting the body's immune response more precisely against cancer cells. Additionally, when combined with pembrolizumab (Keytruda®), which targets the PD-1 pathway, this combination harnesses dual immune pathways, offering a potentially more effective treatment strategy than using pembrolizumab alone. This dual-targeting approach could lead to more robust and sustained anti-tumor activity, providing new hope for patients with difficult-to-treat cancers.

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

Research has shown that XmAb22841, which participants in this trial may receive as monotherapy in Arm 1, is a promising new treatment targeting the area around a tumor. It employs a special type of antibody that focuses on two proteins, CTLA-4 and LAG-3, which cancer cells use to evade the immune system. By blocking these proteins, XmAb22841 may enhance the immune system's ability to attack tumors. In Arm 2 of this trial, XmAb22841 is combined with pembrolizumab (Keytruda®), already proven effective in treating cancers like melanoma and prostate cancer. This combination aims to further boost the immune system's response to tumors. Early studies indicate that patients tolerate these treatments well. ^{1 2 3 6 7}

Who Is on the Research Team?

Benjamin Thompson, MD, PhD

Principal Investigator

Xencor, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• XmAb®22841

How Is the Trial Designed?

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+

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03849469

NCT03849469 | A Study of XmAb®22841 Monotherapy & ... This is a Phase 1, multiple dose, ascending-dose escalation study and expansion study designed to define a maximum tolerated dose and/or recommended dose of ...

2. withpower.com withpower.com/trial/phase-1-melanoma-4-2019-1fcc7

A Study of XmAb®22841 Monotherapy & in Combination w ... Pembrolizumab has been shown to be an effective and safe therapeutic option in various cancers, including melanoma, prostate cancer, and endometrial cancer.

3. biospace.com biospace.com/xencor-doses-first-patient-in-phase-1-study-of-xmab-22841-for-the-treatment-of-patients-with-advanced-solid-tumors

Xencor Doses First Patient in Phase 1 Study of XmAb® ... XmAb22841, a CTLA-4 x LAG-3 bispecific antibody, is Xencor's third tumor microenvironment (TME) activator to enter clinical development.

4. investors.xencor.com investors.xencor.com/news-releases/news-release-details/xencor-reports-initial-dose-escalation-data-phase-1-study

Xencor Reports Initial Dose-Escalation Data from Phase 1 ... XmAb20717 generally well-tolerated and a confirmed complete response (CR) observed at highest dose level tested --.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7650095/

Clinical Data on Immunotherapy in Breast Cancer - PMC This review summarizes key clinical trials, recent findings, and emerging therapeutic concepts in the field of immunotherapy for breast cancer.

6. investors.xencor.com investors.xencor.com/news-releases/news-release-details/xencor-present-preclinical-data-tumor-microenvironment-targeting

Xencor to Present Preclinical Data on Tumor ... The event will feature a discussion on Xencor's tumor microenvironment targeting bispecific oncology pipeline, including XmAb®20717, XmAb®22841, XmAb®23104, and ...

7. sec.gov sec.gov/Archives/edgar/data/1326732/000155837018001202/xncr-20171231x10k.htm

xncr_Current folio_10K The trial is a Phase 1, open-label, multiple-dose, dose escalation study to assess safety, tolerability and preliminary anti-tumor activity in AML. Initial data ...