XmAb®662 + Pembrolizumab for Solid Cancers

No longer recruiting at 2 trial locations

Overseen By Ines Hoffmann

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Xencor, Inc.

Must not be taking: Interleukin-12, Checkpoint inhibitors

Disqualifiers: Uncontrolled disorder, Active CNS involvement, 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 explores a new treatment for individuals with advanced solid tumors unresponsive to standard therapies. It tests XmAb662, an experimental treatment, both alone and with pembrolizumab (KEYTRUDA), to determine a safe and effective dose. The study aims to assess the treatment's tolerance and behavior in the body. Suitable candidates have cancers such as lung, breast, or prostate cancer that have recurred or spread and cannot be cured with existing treatments. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the chance to be among the first to receive this new therapy.

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

The trial requires that you stop certain cancer treatments, like chemotherapy or radiation, at least 4 weeks before starting the study drug. However, palliative radiation is allowed with a 1-week break. The protocol does not specify about other medications, so it's best to discuss with the trial team.

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

Research shows that pembrolizumab, one of the treatments in the trial, is safe for treating certain cancers. The FDA has approved it for patients with specific advanced tumors, indicating thorough safety testing.

For XmAb662, less information is available. It showed promise in early lab studies, but this trial is among the first to test it in humans. Therefore, its safety is not yet fully understood. As this trial is in its early stages, it primarily aims to assess how people tolerate XmAb662, whether used alone or with pembrolizumab.

In summary, pembrolizumab has a well-established safety record, while the safety of XmAb662 remains under study. Participants might experience some unknown effects because XmAb662 is in the early testing phase. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about XmAb662 combined with pembrolizumab because it offers a new approach to fighting solid cancers. Unlike traditional treatments that mainly focus on directly killing cancer cells, XmAb662 enhances the immune system's ability to target cancer by engaging T-cells more effectively. This dual approach, combined with pembrolizumab, an established immunotherapy, could potentially lead to more robust and durable responses in patients. Additionally, XmAb662's novel mechanism of activating immune pathways distinguishes it from current standard treatments, potentially offering new hope for those with cancers that are resistant to existing therapies.

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

Research has shown that pembrolizumab, a treatment in this trial, effectively treats advanced solid tumors, such as certain lung and skin cancers (melanoma). It extends survival by enabling the immune system to attack cancer cells more effectively. XmAb662, another treatment option in this trial, demonstrated in early animal tests that it can fight tumors by boosting key immune cells, like NK cells and T cells, which are crucial in attacking cancer. Although less information exists about XmAb662 in humans, its combination with pembrolizumab is under study in this trial due to its promising potential to enhance the immune system. ^{1 2 5 6 7}

Who Is on the Research Team?

Chet Bohac, MD

Principal Investigator

Executive Medical Director, Clinical Development

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have grown after standard treatment. They must be able to measure the tumor's size, have a life expectancy of at least 3 months, and their body should be functioning well enough to participate. People can't join if they've had severe immune reactions from similar treatments or are currently on certain cancer therapies.

Inclusion Criteria

My cancer cannot be cured, has spread, and did not respond to standard treatments.

I can provide a recent or new tumor sample for the study.

My cancer can be measured or evaluated by specific medical criteria.

Exclusion Criteria

I am currently on a specific treatment plan.

I don't have any uncontrolled health issues besides my cancer.

History of a life-threatening immune-related adverse event related to prior immunotherapy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive XmAb662 monotherapy or in combination with pembrolizumab to evaluate safety and determine recommended dose

3 weeks

Multiple visits for dose escalation monitoring

Dose Expansion

Participants receive the recommended dose to further evaluate safety and efficacy

Up to 2 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• XmAb662

Trial Overview The study tests XmAb662 alone or with Keytruda (pembrolizumab) in patients with various types of advanced cancers. It aims to find a safe and effective dose by observing how patients react and how the drug behaves in their bodies.

How Is the Trial Designed?

Group I: Dose Escalation and Expansion XmAb662 administered in combination with pembrolizumab Experimental Treatment 2 Interventions

Group II: Dose Escalation and Expansion XmAb662 administered as monotherapy Experimental Treatment 1 Intervention

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, 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 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 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 is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[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) 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, 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) 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. investors.xencor.com investors.xencor.com/news-releases/news-release-details/xencor-presents-data-multiple-preclinical-xmabr-bispecific-1

Xencor Presents Data from Multiple Preclinical XmAb ... XmAb662 was selected for further development and demonstrated significant anti-tumor activity in vivo, concurrent with increases in NK cells, T cells, serum IP ...

2. withpower.com withpower.com/trial/phase-1-neoplasms-6-2023-a4fab

XmAb®662 + Pembrolizumab for Solid Cancers Pembrolizumab has shown effectiveness in treating various solid tumors, including non-small cell lung cancer and melanoma, by improving survival rates compared ...

3. firstwordpharma.com firstwordpharma.com/story/5831548

Xencor slides on underwhelming prostate cancer data ... Shares of Xencor fell 14% on Wednesday after the company reported seemingly lacklustre efficacy results – and one patient death – in a Phase ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10357296/

Engineering cytokines for cancer immunotherapy In this review, we focus on the recent progress and competitive landscape in cytokine engineering strategies and preclinical/clinical therapeutics for cancer.

5. investors.xencor.com investors.xencor.com/static-files/08a22135-6d1e-4f6b-839e-b5c7c6316d4e

Xencor R&D Strategy Call co-stimulation only when bound to tumor cells. • Combination with anti-PD1 (pembrolizumab). • In development for patients with solid tumors.

6. ctv.veeva.com ctv.veeva.com/study/a-study-of-xmab-r-662-as-monotherapy-or-in-combination-with-pembrolizumab-in-advanced-solid-tumors

A Study of XmAb®662 as Monotherapy or in Combination ... The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of intravenous administration of XmAb662 monotherapy ...

7. delta.larvol.com delta.larvol.com/Products/?ProductId=d2e4bd5a-5933-40d2-9980-d64c70ec11ce

XmAb662 / Xencor ... data from competitor programs in this class and safety and biomarker data from Xencor's studies." P1 data • Pipeline update • Trial status • Solid Tumor.