Anti-CD137 + Anti-CTLA-4 Monoclonal Antibodies for Advanced Cancer

No longer recruiting at 15 trial locations
AI
Overseen ByAgenus, Inc. Clinical Trial Information
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for advanced solid tumors, a type of cancer that has spread or cannot be removed. The trial aims to assess the safety and tolerability of these treatments when used alone or in combination. Participants will receive either a single treatment or a combination to determine which doses are most effective with minimal side effects. The treatments being tested include AGEN1181 (Botensilimab) and AGEN2373, both monoclonal antibodies. The trial seeks individuals with certain advanced cancers for which standard treatments have failed. Those with a solid tumor that has spread and for whom treatments have not succeeded may find this trial suitable. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive these new therapies.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not clearly specify if you must stop taking your current medications. However, there are specific 'washout' periods (time without taking certain medications) for some treatments, like a 3-week period for cytotoxic agents and a 4-week period for monoclonal antibodies, before starting the study treatment.

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

Research has shown that AGEN2373, when tested alone, was generally well-tolerated by patients with solid tumors. Importantly, it did not cause liver damage, a common concern with similar treatments. Early reports also suggest positive patient responses to this treatment.

Regarding botensilimab, studies have found it effective for patients who did not respond well to other cancer treatments. It was also well-tolerated, even by those with extensive prior treatments.

While these results are promising, it is important to remember that this study is in an early phase. Researchers are still determining the best and safest dose levels. However, both treatments have demonstrated good safety in initial research.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they represent a novel approach for targeting advanced cancer. AGEN1181, AGEN2373, and Botensilimab are monoclonal antibodies that work by engaging the immune system in a unique way. Unlike standard treatments like chemotherapy, these drugs specifically target proteins like CD137 and CTLA-4, which play a crucial role in regulating immune responses against tumors. This dual targeting can potentially enhance the body's ability to fight cancer more effectively while possibly reducing side effects associated with standard therapies. Additionally, the combination therapies being tested may offer a synergistic effect, boosting the overall treatment efficacy.

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

Studies have shown that AGEN2373, one of the treatments in this trial, holds promise for treating advanced solid tumors, whether used alone or with another drug called botensilimab. AGEN2373 strengthens the body's immune response against tumors without causing liver damage, a common side effect of similar treatments. Research indicates that patients who received AGEN2373 alone experienced positive outcomes, even when other treatments failed. In this trial, some participants will receive AGEN2373 alone, while others will receive it with botensilimab to potentially enhance the immune response further. These findings suggest it could effectively fight certain advanced cancers, though more research is needed to confirm these results.15678

Who Is on the Research Team?

MM

Medical Monitor

Principal Investigator

Agenus Inc.

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that have spread or are inoperable, and who've had no success with standard treatments. They must be healthy enough overall, not pregnant, willing to use contraception, and able to provide a recent tumor tissue sample. People can't join if they've recently received certain vaccines or treatments, have severe allergies to human antibodies, uncontrolled health issues like heart disease or infections, mental incapacity, or are pregnant.

Inclusion Criteria

Specific Melanoma Criteria: Inclusion: Histological confirmation of cutaneous melanoma; Progression on or within 24 weeks of stopping treatment with a PD-1/PD-L1 confirmed per Society for Immunotherapy of Cancer (SITC); Patients with BRAF V600-positive tumor(s) should also have received prior treatment with a BRAF inhibitor (alone or in combination with a MEK inhibitor) or have declined targeted therapy. Note: Patients with BRAF V600-positive tumors with no clinically significant tumor-related symptoms nor evidence of rapidly progressive disease are not required to be treated with a BRAF inhibitor (alone or in combination with a MEK inhibitor) based on Investigator's decision.
There is evidence of a measurable disease seen on imaging scans that doctors will use a specific system to evaluate.
I had cancer before, but I finished treatment over 2 years ago and am now cancer-free.
See 12 more

Exclusion Criteria

I have had a transplant of tissue or an organ from another person, except for a cornea transplant.
I am not legally allowed to make my own decisions.
I have not been in a clinical trial for a new treatment or device within the last 3 weeks.
See 16 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AGEN2373 as monotherapy or in combination with botensilimab, with dose escalation to determine the maximum tolerated dose

Up to 2 years
Every 2-4 weeks depending on the treatment arm

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

  • AGEN1181
  • AGEN2373
  • Botensilimab
Trial Overview The trial is testing AGEN2373 alone and combined with botensilimab for safety and effectiveness in treating cancer. It's an early-phase study (Phase 1) where doctors will find the highest dose patients can take without serious side effects by gradually increasing doses for new groups of patients.
How Is the Trial Designed?
5Treatment groups
Experimental Treatment
Group I: Combination Therapy with 3-week AGEN2373 in combination with 6-week BotensilimabExperimental Treatment2 Interventions
Group II: Combination Therapy with 3-week AGEN2373 Monotherapy Lead-In Combination with 6-week BotensilimabExperimental Treatment2 Interventions
Group III: 4-Week Monotherapy with AGEN2373Experimental Treatment1 Intervention
Group IV: 3-Week Monotherapy with AGEN2373Experimental Treatment1 Intervention
Group V: 2-Week Monotherapy with AGEN2373Experimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Agenus Inc.

Lead Sponsor

Trials
58
Recruited
4,900+

Citations

Agenus Presents Positive Efficacy and Safety Outcomes for ...“AGEN2373 has shown meaningful single agent activity and a favorable safety profile without evidence of liver toxicity in patients with heavily ...
Initial findings of the first-in-human phase I study ...Conclusions: AGEN2373 demonstrates good tolerability in pts with advanced solid tumors, with a safety profile characterized by a lack of ...
A phase 1 study of AGEN2373, a novel CD137 agonist ...Key endpoints included safety, tolerability, PK, preliminary efficacy, and PD markers. Imaging was Q8W. Results: Pts were enrolled between Oct 2019 and May 2022 ...
NCT04121676 | Anti-CD137 and Anti-CTLA-4 Monoclonal ...This study is an open-label, Phase 1, multicenter study to evaluate the safety, tolerability, PK, and PD profiles of AGEN2373 as a monotherapy and in ...
377 AGEN2373 is a CD137 agonist antibody designed to ...Patients with advanced solid cancers, treated with AGEN2373 up to 1 mg/kg every 4 weeks, demonstrate clinical activity with no evidence of ...
6.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/27756788/
Results from an Integrated Safety Analysis of Urelumab ...Purpose: Urelumab is an agonist antibody to CD137 with potential application as an immuno-oncology therapeutic. Data were analyzed to assess ...
Results from an Integrated Safety Analysis of Urelumab, an ...Data were analyzed to assess safety, tolerability, and pharmacodynamic activity of urelumab, including the dose selected for ongoing development in patients ...
A phase 1 study of AGEN2373, a novel CD137 agonist ...AGEN2373 showed objective responses as monotherapy in heavily pretreated pts with solid tumors and was well-tolerated with no evidence of hepatotoxicity.
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