HPN328 + Atezolizumab for Small Cell Lung Cancer

Recruiting at 10 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

232 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for individuals with advanced small cell lung cancer and related cancers. It tests the safety and effectiveness of a drug called gocatamig (HPN328), both alone and in combination with Atezolizumab (Tecentriq) or another drug, I-DXd. The goal is to determine the optimal dose and understand how the body processes these drugs. Individuals with confirmed cancer that did not respond to previous treatments might be suitable candidates for this trial. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial group, offering participants early access to potentially groundbreaking 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.

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

Research has shown that HPN328, also known as gocatamig, is generally well-tolerated by patients with small cell lung cancer (SCLC) and other advanced cancers. In earlier studies, patients who took gocatamig found it manageable, and it demonstrated positive effects. These studies continue to determine the best dose and monitor for any side effects.

When combined with atezolizumab, research indicates that HPN328 remains well-tolerated. Atezolizumab has been used in cancer treatments before and is approved by the FDA for other uses, confirming its safety profile. Although combining these drugs might cause new side effects, current data suggests that any side effects are manageable.

The study is in its early stages, focusing on finding the right dose and closely monitoring for any side effects. This is a normal part of the process to ensure safety before testing on larger groups of patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments being tested for small cell lung cancer (SCLC) because they offer new approaches compared to the current standard of care, which often includes chemotherapy and immunotherapy. The study treatments involve gocatamig, a novel drug administered via intravenous infusion, which is being tested alone and in combination with other agents like atezolizumab and I-DXd. Gocatamig's unique mechanism involves targeting specific cancer pathways, potentially offering more precise treatment options. Additionally, the combination of gocatamig with atezolizumab aims to enhance the immune system's ability to fight cancer cells, while the pairing with I-DXd explores synergistic effects that could improve outcomes. These innovative treatment strategies could lead to more effective and personalized approaches for SCLC patients.

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

Research has shown that HPN328 is active in treating small cell lung cancer (SCLC). It targets a protein called DLL3, commonly found in SCLC tumors, and aids T-cells in attacking the cancer. Studies indicate that HPN328 is generally well-tolerated and can effectively target and destroy cancer cells with DLL3.

In this trial, some participants will receive HPN328 combined with Atezolizumab, an immune therapy that has improved survival rates in SCLC when used with chemotherapy. This combination might enhance the body's immune response against cancer. Although more data is needed, early results suggest it could effectively fight SCLC. ^{4 5 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• HPN328

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.

How Is the Trial Designed?

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.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

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

Published Research Related to This Trial

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 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]

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, 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, 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04471727

NCT04471727 | A Study in Participants With Advanced ... This study will investigate the maximum tolerated dose, the recommended dose for expansion (RDE), safety, efficacy, and pharmacokinetics of gocatamig alone, ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02721-7/fulltext

698P Interim results from a phase I/II study of HPN328, a tri ... HPN328 has 3 binding domains including anti-DLL3 for target engagement, anti-albumin for half-life extension, and anti-CD3 for T cell engagement and activation.

3. conference-correspondent.com conference-correspondent.com/highlights/esmo/dll3-targeting-t-cell-engager-hpn328-shows-clinical-activity-in-sclc-and-nen

DLL3-Targeting T-Cell Engager HPN328 Shows Clinical ... Date of data cutoff was September 12, 2023. A total of 71 patients received HPN328. Of these, 64.8% had SCLC, 15.5% had neuroendocrine prostate cancer, and 19.7 ...

4. withpower.com withpower.com/trial/phase-2-small-cell-lung-carcinoma-11-2020-7a845

HPN328 + 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 ...

5. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/260483

A Study in Participants With Advanced Cancers Associated ... This study will investigate the maximum tolerated dose, the recommended dose for expansion (RDE), safety, efficacy, and pharmacokinetics of ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8090

Updated results from a phase 1/2 study of HPN328, a tri- ... HPN328 is well tolerated and clinically active in SCLC, NEC, and NEPC. Current dose optimization cohorts have completed enrollment and data continue to mature.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06780137

NCT06780137 | A Study to Evaluate the Safety and ... This study will consist of two parts. Part 1 will assess the safety, tolerability, and efficacy of gocatamig and I-DXd at doses determined in study MK-6070-001.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1556086424009341

OA10.06 Impact of Brain Metastases on Safety and Efficacy ... We analyzed the characteristics and outcomes of pts with SCLC treated to date in the MK-6070 phase 1/2 study (NCTNCT04471727) according to the presence of BM.