AB248 + Pembrolizumab for Cancer

Not currently recruiting at 30 trial locations

Overseen By Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Asher Biotherapeutics, Inc.

Must not be taking: Steroids, Immunosuppressants, IL-2 agents, others

Disqualifiers: Immunodeficiency, CNS metastases, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with advanced solid tumors, which are cancers that form in solid organs or tissues. Researchers aim to determine if the new drug, AB248 (CD8+ T cell-selective IL-2), is safe and effective alone or when combined with pembrolizumab, a medication that aids the immune system in fighting cancer. The trial seeks participants with solid tumors that cannot be cured or have metastasized. Those experiencing further spread of this type of cancer may find this trial suitable. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received prior systemic anticancer therapy within 4 weeks before the study or be on chronic systemic steroid therapy within 7 days before the study.

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

Research has shown that early data for etakafusp alfa (AB248) indicates it is generally well-tolerated. This treatment activates certain immune cells called CD8+ T cells, which help fight tumors. So far, studies have revealed promising anti-tumor activity with positive outcomes and a favorable safety profile.

When combined with pembrolizumab, a drug often used to treat cancer, the two treatments appear to work well together. Pembrolizumab is already approved for several cancers, so its safety is well-known and acceptable.

Since researchers are testing AB248 in humans for the first time, they are closely monitoring its safety both alone and with pembrolizumab. New data will help confirm how well people tolerate these treatments in the future. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard cancer treatments, which often rely on chemotherapy or radiation, AB248 offers a new approach by utilizing etakafusp alfa, an innovative active ingredient that enhances the immune system's ability to target cancer cells more precisely. Researchers are excited about AB248 in combination with pembrolizumab because it may amplify the effectiveness of immunotherapy, potentially leading to better outcomes with fewer side effects. This combination targets specific immune pathways, which could provide more personalized and effective treatment options for patients.

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

Research has shown that etakafusp alfa (AB248) specifically activates certain immune cells called CD8+ T cells, which play a crucial role in fighting cancer. Early studies have indicated positive signs of its potential to combat tumors. In this trial, some participants will receive etakafusp alfa (AB248) alone, while others will receive it in combination with pembrolizumab. Pembrolizumab, a drug already proven effective against some cancers, aids the immune system in identifying and attacking cancer cells. Together, these treatments could enhance the body's ability to target and destroy cancer cells more effectively. ^{1 2 3 5 6}

Who Is on the Research Team?

Medical Monitor

Principal Investigator

Asher Biotherapeutics, Inc.

Are You a Good Fit for This Trial?

Adults over 18 with advanced or metastatic solid tumors, including specific cancers like lung and kidney cancer. Participants must have measurable disease, be in good physical condition (ECOG 0-1), and not have had recent cancer treatments or other anticancer therapies while on the study. They can't join if they have active infections, autoimmune diseases, a history of severe allergies to similar drugs, or are taking immunosuppressants.

Inclusion Criteria

Your disease can be measured using specific guidelines by the local doctor or radiologist.

Meets pregnancy prevention requirements

My organs are functioning well according to recent tests.

Exclusion Criteria

You currently have an autoimmune disease that is not controlled.

I am currently being treated for an infection.

Inability to comply with study and follow-up procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive AB248 alone or in combination with pembrolizumab to determine the safety and optimal dosing

Up to 24 months

Dose Expansion

Participants receive AB248 alone or in combination with pembrolizumab in disease-specific cohorts to further evaluate safety and efficacy

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

What Are the Treatments Tested in This Trial?

Interventions

• AB248
• Pembrolizumab

Trial Overview The trial is testing AB248 alone or combined with Pembrolizumab for safety and effectiveness against various advanced solid tumors. It's an early-stage trial that includes increasing doses to find safe levels followed by further testing at those levels.

How Is the Trial Designed?

Group I: etakafusp alfa (AB248) Monotherapy Indication Expansion Experimental Treatment 1 Intervention

etakafusp alfa (AB248) will be administered intravenously as a single agent in disease specific cohorts

Group II: etakafusp alfa (AB248) Monotherapy Dose-Escalation Experimental Treatment 1 Intervention

etakafusp alfa (AB248) will be administered intravenously as a single agent

Group III: etakafusp alfa (AB248) + pembrolizumab Combination Indication Expansion Experimental Treatment 2 Interventions

etakafusp alfa (AB248) and pembrolizumab will be administered intravenously in disease specific cohorts

Group IV: etakafusp alfa (AB248) + pembrolizumab Combination Dose-Escalation Experimental Treatment 2 Interventions

etakafusp alfa (AB248) and pembrolizumab will be administered intravenously

Who Is Running the Clinical Trial?

Asher Biotherapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

550+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

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 monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

In a review of 567 reports of immune-mediated necrotizing myopathy (IMNM), 14 cases were associated with pembrolizumab, indicating a significant link between this treatment and the adverse event, with a reporting odds ratio of 17.59.

The study emphasizes the importance of updated diagnostic criteria for IMNM and suggests that better collaboration between oncologists and neurologists is needed to address these neurological complications related to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-mediated necrotizing myopathy with pembrolizumab: a specific neuromuscular entity. Trenque, T., Lepoix, E., Trenque, A., et al.[2022]

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) 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, 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 is an effective monoclonal antibody that targets the PD-1 immune checkpoint, helping to restore T cell anti-tumor responses, and is administered at a dose of 200 mg every 3 weeks until disease progression or for up to 24 months.

It has received approval for treating various cancers, including melanomas and non-small cell lung cancers, particularly in tumors that are hypermutated or express PD-L1, but ongoing research aims to expand its use to less immunogenic tumor types through combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. du Rusquec, P., de Calbiac, O., Robert, M., 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05653882

NCT05653882 | A Study Evaluating AB248 Alone or in ... This is a phase I, First-in-Human (FIH), open-label study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and preliminary efficacy of ...

2. asherbio.com asherbio.com/2025/01/08/asher-bio-announces-clinical-trial-collaboration-and-supply-agreement-on-etakafusp-alfa-ab248-in-combination-with-bispecific-t-cell-engager-in-patients-with-small-cell-lung-cancer/

Asher Bio Announces Clinical Trial Collaboration and ... “Based on emerging data to date, we believe etakafusp alfa has the potential to improve the efficacy of T cell engagers (TCEs) by selectively ...

3. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/asher-biotherapeutics-ab248-rilvegostomig-in-nsclc-phase-1b-2-study-announced/

Asher Biotherapeutics AB248 & Rilvegostomig in NSCLC Preliminary data from a Phase 1a/1b trial of etakafusp alfa demonstrate its ability to selectively activate CD8+ T cells, showing promising anti ...

4. synapse.patsnap.com synapse.patsnap.com/article/asher-bio-announces-trial-collaboration-for-etakafusp-alfa-with-t-cell-engager-in-small-cell-lung-cancer

Asher Bio Announces Trial Collaboration for Etakafusp Alfa ... Preliminary data from the trial has shown strong, selective CD8+ T cell activation with positive evidence of anti-tumor activity and a favorable ...

5. withpower.com withpower.com/trial/phase-1-tumors-solid-11-2022-71dea

AB248 + Pembrolizumab for Cancer · Info for Participants Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non- ...

6. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05653882

AB248 Alone or in Combination With Pembrolizumab in Adult ... This is a phase I, First-in-Human (FIH), open-label study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and preliminary efficacy of AB248.