What side effects are associated with this type of intervention?

Common treatments for Small Cell Lung Cancer (SCLC) include immune checkpoint inhibitors like Atezolizumab and novel agents targeting DLL3, such as HPN328. Atezolizumab can cause side effects such as fatigue, cough, nausea, decreased appetite, and rash. More severe side effects include immune-mediated reactions like pneumonitis, hepatitis, colitis, and endocrinopathies. Novel agents targeting DLL3, like HPN328, are still under investigation, but potential side effects may include infusion-related reactions, fatigue, and gastrointestinal symptoms. Traditional chemotherapy for SCLC often results in side effects like hair loss, nausea, vomiting, fatigue, and increased risk of infections due to bone marrow suppression.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors for the treatment of Small Cell Lung Cancer (SCLC). Atezolizumab, targeting PD-L1, is approved for use in combination with carboplatin and etoposide for extensive-stage SCLC. Another notable immune checkpoint inhibitor is Nivolumab, which targets PD-1 and has been approved for patients with metastatic SCLC with disease progression after platinum-based chemotherapy and at least one other line of therapy. While there are no FDA-approved therapies specifically targeting DLL3 in SCLC, investigational agents like HPN328 are being studied for their potential efficacy in this area.

What other types of research exist?

Promising novel alternatives for SCLC treatment in 2024 include: 1) Rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate targeting DLL3, which has shown potential in clinical trials. 2) Lurbinectedin, a novel agent that has received accelerated approval by the FDA for SCLC based on its efficacy in clinical trials. 3) Pembrolizumab, another immune checkpoint inhibitor targeting PD-1, which has shown efficacy in SCLC patients, especially those with high PD-L1 expression.

← Back to Search

Monoclonal Antibodies

HPN328 + Atezolizumab for Small Cell Lung Cancer

Phase 1 & 2

Recruiting

Research Sponsored by Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Eligibility Criteria Checklist

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

Must have

Histologically or cytologically confirmed malignancy associated with expression of DLL3

Adequate renal function: Calculated creatinine clearance ≥50 mL/min using the formula of Cockcroft and Gault

Must not have

Untreated central nervous system (CNS) metastases

Patients with glioma or other primary CNS malignancy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to ~4 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug, HPN328, alone and with another drug, Atezolizumab, in patients with advanced cancers that have a specific protein called DLL3. The goal is to see if these treatments can help the immune system find and destroy cancer cells. This is aimed at patients whose cancers are hard to treat with standard therapies.

Who is the study for?

This trial is for adults with advanced cancers that show DLL3 protein, like small cell lung cancer. They must have good kidney and liver function, stable blood counts, and a tissue sample available. People can't join if they have untreated brain metastases, certain neurological conditions, severe allergies to specific drugs or components used in the study treatments, active autoimmune diseases or immune deficiencies.

What is being tested?

The study is testing HPN328 alone and combined with Atezolizumab in patients whose cancers express the DLL3 protein. It's an early-phase trial to find out how safe these treatments are and how the body processes them.

What are the potential side effects?

Possible side effects include reactions related to the immune system such as inflammation of organs (like lungs), infusion-related reactions which may cause symptoms during or after administration of treatment, allergic responses due to drug formulation ingredients.

Eligibility Criteria

Inclusion Criteria

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

Select...

My cancer shows DLL3 protein presence.

Select...

My kidneys work well enough, with a creatinine clearance rate of 50 mL/min or more.

Select...

My liver tests are within the normal range.

Select...

I can provide a tissue sample from a previous or new biopsy.

Select...

My blood counts meet the required levels for treatment.

Exclusion Criteria

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

Select...

I have brain metastases that have not been treated.

Select...

I have a brain tumor.

Select...

I have spinal cord compression or uncontrolled back pain due to cancer.

Select...

I have a history of lung scarring or inflammation not caused by infections.

Select...

I have had bleeding in my brain or spinal cord.

Select...

I have a nervous system disorder related to my cancer.

Select...

I have or had an autoimmune disease or immune deficiency.

Select...

I frequently need procedures to remove excess fluid from my chest or abdomen.

Select...

I have had a stem cell or organ transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to ~4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to ~4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to ~4 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

AC of I-DXd

AC of atezolizumab

AUCinf of I-DXd

+42 more

Secondary study objectives

Best Overall Response (BOR)

Duration of extra-cranial response (EC-DOR)

Duration of response (DOR)

+8 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

5Treatment groups

Experimental Treatment

Group I: MK-6070 monotherapy dose escalation with 3 week dosing intervalExperimental Treatment1 Intervention

Participants will receive MK-6070 via IV infusion once every 3 weeks (Q3W) of a 21-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation, or the Sponsor decides to stop enrollment.

Group II: MK-6070 monotherapy dose escalation with 2 week dosing intervalExperimental Treatment1 Intervention

Participants will receive MK-6070 via IV infusion once every 2 weeks (Q2W) of a 28-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation, or the Sponsor decides to stop enrollment.

Group III: MK-6070 monotherapy dose escalation with 1 week dosing intervalExperimental Treatment1 Intervention

Participants will receive MK-6070 once weekly (Q1W) via intravenous (IV) infusion during each 21-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation or the Sponsor decides to stop enrollment.

Group IV: MK-6070 dose escalation with atezolizumabExperimental Treatment2 Interventions

Small cell lung cancer (SCLC) participants will receive MK-6070 via IV infusion Q2W during each 28-day cycle and Atezolizumab via IV infusion every 4 weeks (Q4W) on Day 1 of each 28-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation, or the Sponsor decides to stop enrollment.

Group V: MK-6070 dose escalation in combination with I-DXdExperimental Treatment2 Interventions

SCLC participants will receive MK-6070 via IV infusion Q2W during each 42-day cycle and I-DXd via IV infusion Q3W on Day 1 and Day 22 of each 42-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation, or the Sponsor decides to stop enrollment.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Atezolizumab

2016

Completed Phase 3

~5860

0 / 14Eligibility 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

The most common treatments for Small Cell Lung Cancer (SCLC) include immune checkpoint inhibitors and novel therapeutic agents targeting specific cancer markers. Atezolizumab, an immune checkpoint inhibitor, works by targeting PD-L1, a protein that helps cancer cells evade the immune system. By inhibiting PD-L1, Atezolizumab enhances the body's immune response against cancer cells, leading to improved survival rates. HPN328, a novel therapeutic agent, targets DLL3, a protein commonly expressed in SCLC cells but not in normal tissues. By binding to DLL3, HPN328 can deliver cytotoxic agents directly to cancer cells, minimizing damage to healthy cells. These treatments are significant for SCLC patients as they offer targeted approaches that can improve efficacy and reduce side effects compared to traditional chemotherapy.

Integrating Immunotherapy and Targeted Therapy in Cancer Treatment: Mechanistic Insights and Clinical Implications.Immune evasion and current immunotherapy strategies in mycosis fungoides (MF) and Sézary syndrome (SS).Immunotherapy in extensive small cell lung cancer.