HPN328 + Atezolizumab for Small Cell Lung Cancer

Recruiting at 10 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Must not be taking: Immunosuppressants, Immunostimulatory agents

Disqualifiers: CNS metastases, Autoimmune disease, Cardiovascular disease, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on immunosuppressive medications, you need to stop them at least 2 weeks before starting the trial treatment.

What data supports the effectiveness of the drug Atezolizumab for Small Cell Lung Cancer?

Atezolizumab has been shown to improve survival outcomes in patients with extensive-stage small cell lung cancer when combined with chemotherapy, as demonstrated in the IMpower133 trial. It is also approved for use in other cancers like bladder cancer, where it has shown durable tumor responses and improved survival rates. ^{1 2 3 4 5}

What safety data exists for Atezolizumab in humans?

Atezolizumab has been shown to have an acceptable safety profile in clinical trials for various cancers, including non-small cell lung cancer and bladder cancer. Common side effects include fatigue, decreased appetite, and nausea, while more serious effects can include pneumonia and liver inflammation. Overall, it is considered to have a manageable safety profile. ^{2 4 5 6 7}

How is the drug HPN328 + Atezolizumab unique for treating small cell lung cancer?

The drug combination of HPN328 and Atezolizumab is unique because Atezolizumab is a monoclonal antibody that blocks PD-L1, a protein that helps cancer cells evade the immune system, thereby boosting the body's immune response against the cancer. This approach is different from traditional chemotherapy, which directly targets and kills cancer cells. ^{2 4 5 8 9}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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.

Inclusion Criteria

My cancer shows DLL3 protein presence.

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

My liver tests are within the normal range.

Exclusion Criteria

I have brain metastases that have not been treated.

I have a brain tumor.

You are allergic to medications made from Chinese hamster ovary cells or any part of the atezolizumab formulation, or other similar medications.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive gocatamig monotherapy or in combination with Atezolizumab or I-DXd to determine the maximum tolerated dose and recommended dose for expansion

21-42 days per cycle

Weekly or bi-weekly visits for IV infusion

Dose Expansion

Participants receive treatment at the recommended dose to further assess safety and efficacy

Varies based on response and tolerance

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

Treatment Details

Interventions

• Atezolizumab (Monoclonal Antibodies)
• HPN328 (Monoclonal Antibodies)

Trial Overview 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.

Participant Groups

Group I: Gocatamig monotherapy dose escalation with 3 week dosing interval Experimental Treatment 1 Intervention

Participants will receive gocatamig 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: Gocatamig monotherapy dose escalation with 2 week dosing interval Experimental Treatment 1 Intervention

Participants will receive gocatamig 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: Gocatamig monotherapy dose escalation with 1 week dosing interval Experimental Treatment 1 Intervention

Participants will receive gocatamig 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: Gocatamig dose escalation with atezolizumab Experimental Treatment 2 Interventions

Small cell lung cancer (SCLC) participants will receive gocatamig 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: Gocatamig dose escalation in combination with I-DXd Experimental Treatment 2 Interventions

SCLC participants will receive gocatamig 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.

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

4

Recruited

530+

Harpoon Therapeutics

Lead Sponsor

Trials

4

Recruited

530+

Daiichi Sankyo

Industry Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Findings from Research

In a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, combined with carboplatin and etoposide, significantly improves overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, based on data from the IMpower133 trial involving previously untreated patients.

The treatment regimen is generally well tolerated, with no new safety concerns identified, and it does not negatively impact patients' quality of life, making it a valuable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. Frampton, JE.[2021]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

In a phase 1 study involving 17 patients with relapsed or refractory small-cell lung cancer (SCLC), atezolizumab was generally well tolerated, with 64.7% experiencing any-grade treatment-related adverse events, the most common being fatigue.

Atezolizumab showed some antitumor activity, with a partial response in 5.9% of patients and a median overall survival of 5.9 months, suggesting potential benefits for patients with high T-effector gene signature and PD-L1 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. Chiang, AC., Sequist, LVD., Gilbert, J., et al.[2021]

Atezolizumab, an immune checkpoint inhibitor, has been shown to significantly prolong overall survival in patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy, based on results from the phase II POPLAR and phase III OAK trials.

The treatment is particularly effective in patients with higher PD-L1 expression, demonstrating higher objective response rates, and it has a manageable safety profile with a low incidence of immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. Blair, HA.[2020]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., et al.[2022]

Atezolizumab, an immunotherapy targeting PD-L1, has shown promising efficacy in treating non-small-cell lung cancer (NSCLC), particularly in clinical trials like the phase II FIR and BIRCH studies, which evaluated its effectiveness based on PD-L1 expression.

In randomized trials (POPLAR and OAK), atezolizumab demonstrated improved efficacy compared to standard chemotherapy (docetaxel) in previously treated NSCLC patients, suggesting a favorable risk-benefit ratio for second-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospects and progress of atezolizumab in non-small cell lung cancer. Vansteenkiste, J., Wauters, E., Park, K., et al.[2019]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. [2021]

6. France pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Prospects and progress of atezolizumab in non-small cell lung cancer. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]