What side effects are associated with this type of intervention?

Common side effects of PD-1/PD-L1 inhibitors, such as pembrolizumab, used in the treatment of stomach cancer include fatigue, diarrhea, rash, and nausea. Severe adverse effects can include pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. For treatments involving 4-1BB agonism, potential side effects may include liver toxicity, cytokine release syndrome, and immune-related adverse events. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has been approved by the FDA for the treatment of PD-L1-positive advanced gastric or gastroesophageal junction adenocarcinoma. This approval is based on clinical trials demonstrating its efficacy in improving overall survival and maintaining quality of life compared to chemotherapy. While specific FDA approvals for treatments involving 4-1BB agonism in stomach cancer are not mentioned, ongoing research and trials like INBRX-105 are exploring the potential of combining PD-L1 inhibition with 4-1BB agonism to enhance anti-tumor immune responses.

What other types of research exist?

Promising novel alternatives to INBRX-105 for stomach cancer patients in 2024 include: 1) Pembrolizumab (PD-1 inhibitor) combined with other agents like chemotherapy or targeted therapies, 2) Nivolumab (PD-1 inhibitor) in combination with ipilimumab (CTLA-4 inhibitor), 3) Ramucirumab (VEGFR-2 antagonist) combined with paclitaxel, and 4) Emerging bispecific antibodies or CAR-T cell therapies targeting specific tumor antigens. These options are based on their mechanisms of action and recent clinical advancements.

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Monoclonal Antibodies

INBRX-105 + Pembrolizumab for Head and Neck Cancer (PDL1x41BB Trial)

Phase 1

Waitlist Available

Research Sponsored by Inhibrx Biosciences, Inc

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1

Patients with relapsed or refractory non-small cell lung cancer, cutaneous melanoma, head and neck squamous cell carcinoma, MSI/TMB-high or MMRd solid tumors

Must not have

Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or other immunosuppressive medications

Anti-infectious drug treatments (i.e., antibiotics) within 4 weeks prior to the first dose of study drug

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2-3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug, INBRX-105, alone and with Pembrolizumab, to help the immune system fight cancer in patients who may not respond to standard treatments. Pembrolizumab is an FDA-approved medication used in various cancers, including advanced non-small cell lung cancer and metastatic melanoma.

Who is the study for?

This trial is for adults with certain advanced solid tumors, including lung, head and neck, stomach, kidney cancers and melanoma. Participants must have tried standard treatments without success or have no other options available. They should be in good physical condition (ECOG PS of 0 or 1) and have proper organ function. Those with untreated non-small cell lung cancer (NSCLC) must show a specific level of PD-L1 protein presence.

What is being tested?

The study tests INBRX-105 alone and combined with Pembrolizumab in patients to find the safest dose that can be tolerated. INBRX-105 is an innovative antibody targeting two proteins on cancer cells: PD-L1 which helps them hide from the immune system, and 4-1BB which activates T-cells against the tumor.

What are the potential side effects?

Possible side effects include reactions related to immune system activation such as inflammation in various organs, skin rashes, fatigue, changes in blood counts leading to increased infection risk or bleeding tendencies. Specific side effects will depend on how each patient's body reacts to the treatment.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or can carry out light work.

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My cancer has returned or didn't respond to treatment, and it's one of the specified types.

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My cancer has spread, doesn't respond to treatment, and can't be surgically removed.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My cancer has spread, doesn't respond to treatment, and there are no standard treatments left.

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My cancer has spread and cannot be removed by surgery, and standard treatments have not worked or are not suitable for me.

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My cancer has spread and doesn't respond to standard treatments.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have or had lung inflammation treated with steroids or other immune-suppressing drugs.

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I haven't taken antibiotics in the last 4 weeks.

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I have a blood cancer such as leukemia, lymphoma, or myeloma.

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I have had an organ or bone marrow transplant.

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I have been treated with 4-1BB agonists before.

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I have not had major surgery in the last 4 weeks.

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I do not have recent severe heart issues or uncontrolled high blood pressure.

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I have not had a serious lung blood clot in the last 3 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2-3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2-3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2-3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Frequency of adverse events of INBRX-105

Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-105

Severity of adverse events of INBRX-105

Secondary study objectives

Area under the serum concentration time curve (AUC) of INBRX-105

Immunogenicity of INBRX-105

Maximum observed serum concentration (Cmax) of INBRX-105

+2 more

Other study objectives

Anti-tumor activity of INBRX-105

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

11Treatment groups

Experimental Treatment

Group I: Single Agent EscalationExperimental Treatment1 Intervention

INBRX-105 will be escalated in patients with locally advanced or metastatic solid tumors.

Group II: INBRX-105 Escalation in Combination with PembrolizumabExperimental Treatment2 Interventions

INBRX-105 will be escalated in combination with Pembrolizumab in pateitns with locally advanced or metastatic solid tumors.

Group III: Expansion Cohort PD-L1 Positive BasketExperimental Treatment1 Intervention

Patients with gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with single-agent INBRX-105 at either the MTD or RP2D.

Group IV: Expansion Cohort Non-small Cell Lung CancerExperimental Treatment1 Intervention

Patients will be treated with single-agent INBRX-105 at either the MTD or RP2D.

Group V: Expansion Cohort Nasopharyngeal or Oropharyngeal CarcinomaExperimental Treatment1 Intervention

Patients with head and neck squamous cell carcinoma (NPC or OPC) will be treated with single-agent INBRX-105 at either the MTD or RP2D.

Group VI: Expansion Cohort MelanomaExperimental Treatment1 Intervention

Patients will be treated with single-agent INBRX-105 at either the MTD or RP2D.

Group VII: Combination Expansion Cohort Non-small Cell Lung CancerExperimental Treatment2 Interventions

CPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab.

Group VIII: Combination Expansion Cohort MelanomaExperimental Treatment2 Interventions

CPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab.

Group IX: Combination Expansion Cohort Cohort PD-L1 Positive BasketExperimental Treatment2 Interventions

CPI-relapsed/refractory patients with head and neck squamous cell carcinoma, gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with INBRX-105 in combination with Pembrolizumab.

Group X: Combination Expansion Cohort CPI Naive Non-small Cell Lung CancerExperimental Treatment2 Interventions

CPI naive patients (PD-L1 IHC between 1 and 49%) will be treated with INBRX-105 in combination with Pembrolizumab.

Group XI: Combination Expansion Cohort CPI Naive HNSCCExperimental Treatment1 Intervention

CPI naive patients (PD-L1 IHC \>50%) will be treated with INBRX-105 in combination with Pembrolizumab.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for stomach cancer include immune checkpoint inhibitors like pembrolizumab and nivolumab, which target the PD-1/PD-L1 pathway. These drugs work by blocking the interaction between PD-1 on T-cells and PD-L1 on tumor cells, thereby enhancing the immune system's ability to attack cancer cells. Additionally, 4-1BB agonists, such as those being studied in the INBRX-105 trial, provide localized T-cell co-stimulation, further boosting the immune response against the tumor. These mechanisms are crucial for stomach cancer patients as they offer a targeted approach to enhance the body's natural defenses, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

Compound-therapy based on cancer-immunity cycle: promising prospects for antitumor regimens.Characteristics of Real-World Metastatic Non-Small Cell Lung Cancer Patients Treated with Nivolumab and Pembrolizumab During the Year Following Approval.The challenge of targeted therapies for gastric cancer patients: the beginning of a long journey.