RO7616789 for Small Cell Lung Cancer

No longer recruiting at 29 trial locations

Overseen By Reference Study ID Number: BP44382 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hoffmann-La Roche

Must not be taking: QT prolonging drugs

Disqualifiers: Pregnancy, Poorly controlled diabetes, CNS disease, others

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

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, RO7616789, to determine its safety and effectiveness for individuals with advanced small cell lung cancer (SCLC) or neuroendocrine carcinoma (NEC) that has recurred after treatment. The trial aims to understand the drug's mechanism in the body and its potential to combat tumors. It includes different parts to identify the optimal dosage and further assess the drug's effects. Individuals who have been treated for SCLC or NEC, still have measurable disease, and have a life expectancy of at least 12 weeks might be suitable candidates. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications for the trial?

The trial requires stopping any anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, at least 21 days before starting the study treatment. Also, you cannot take medications that are known to prolong the QT interval. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Will I have to stop taking my current medications?

The trial requires that you stop any anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, at least 21 days before starting the study treatment. Additionally, you cannot be on medications that are known to prolong the QT interval.

Is there any evidence suggesting that RO7616789 is likely to be safe for humans?

Research shows that RO7616789 is in the early stages of testing to determine its safety for humans. Since detailed safety information isn't available yet, the trial is closely monitoring safety. Researchers are primarily assessing how well participants tolerate the treatment and checking for any side effects.

In this type of study, participants receive different doses to identify the safest amount. If side effects occur, researchers can adjust the dose. This careful approach helps ensure the treatment is as safe as possible for participants.

RO7616789 is being tested for small cell lung cancer and neuroendocrine carcinoma. Although specific safety results from the trials are not yet available, initial human testing suggests some confidence in its safety. Safety remains the main focus at this stage, and researchers are working to ensure the treatment is well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about RO7616789 for small cell lung cancer because it introduces a novel dosing approach with potential benefits over the standard chemotherapy and immunotherapy options currently available. Unlike traditional treatments, RO7616789 is being tested with flexible dosing schedules, allowing for weekly or every-three-week intravenous administration, which could better accommodate patient needs and manage side effects. This flexibility, combined with the possibility of adjusting the dose based on individual patient tolerance, may lead to a more personalized and potentially more effective treatment option for patients with this aggressive cancer type.

What evidence suggests that RO7616789 might be an effective treatment for small cell lung cancer?

Research shows that RO7616789 targets a protein called DLL3, present in many cancer cells but absent in healthy cells. This makes it a promising treatment for small cell lung cancer (SCLC) and neuroendocrine carcinoma (NEC). Early lab studies have demonstrated that targeting DLL3 can help the immune system attack cancer cells more effectively. In this trial, participants will receive RO7616789 in different dosing regimens to evaluate its safety and effectiveness. Although data collection from human trials is ongoing, early tests have shown promise. This strategy positions RO7616789 as a potential new option for patients with these hard-to-treat cancers. ^{1 2 3 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with advanced small cell lung cancer or neuroendocrine carcinoma who have relapsed after at least one systemic therapy. They should be able to live more than 12 weeks, be relatively active (ECOG status of 0 or 1), and have organs functioning well enough for treatment. Pregnant women can't participate, and participants must use contraception.

Inclusion Criteria

You must have a negative pregnancy test.

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

My blood and organs are functioning well.

Exclusion Criteria

I have had a stem cell or organ transplant in the past.

I do not have a history of brain cancer, untreated brain metastases, or major neurological conditions.

I have had a severe immune reaction to previous cancer immunotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Part 1

Participants receive a fixed dose of RO7616789 intravenously once weekly on Day 1, 8, and 15 of each 21-day cycle

Varies

3 visits per 21-day cycle

Dose Escalation Part 2

Participants receive a fixed dose of RO7616789 intravenously once every 3 weeks on Day 1 of each 21-day cycle

Varies

1 visit per 21-day cycle

Dose Expansion Part 3

Further investigation of one or more dosing regimens based on emerging data from Part 1 and 2

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 26 months

What Are the Treatments Tested in This Trial?

Interventions

• RO7616789

Trial Overview The study tests RO7616789's safety and how it affects the body and tumors in patients with certain cancers. It has three parts: increasing doses to find a safe level (Dose Escalation) and then giving that dose to more people (Dose Expansion).

How Is the Trial Designed?

Group I: Part 3: Dose Expansion Experimental Treatment 2 Interventions

Based on emerging data from Part 1 and 2, one or more dosing regimens will be further investigated in Part 3.

Group II: Part 2: RO7616789 Q3W: Dose Escalation Experimental Treatment 2 Interventions

Participants will receive a fixed dose of RO7616789, at a dose determined in Part 1, intravenously once every 3 weeks (Q3W) on Day 1 of each 21-day cycle. In case of toxicity, step-up (single or double) dosing may be explored.

Group III: Part 1: RO7616789 QW: Dose Escalation Experimental Treatment 2 Interventions

Participants will receive a fixed dose of RO7616789 intravenously once weekly (QW) per dose level on Day 1, 8, and 15 of each 21-day cycle. In case of toxicity, step-up (single or double) dosing may be explored.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

The combination of the anti-PD-1 antibody budigalimab and the antibody-drug conjugate Rova-T was found to be tolerated in 31 patients with previously treated small cell lung cancer (SCLC), with common side effects including pleural effusion, fatigue, and cough.

This combination therapy showed an overall response rate of 24.1%, with one complete response and six partial responses, indicating promising efficacy despite the discontinuation of Rova-T's development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. Calvo, E., Spira, A., Miguel, M., et al.[2022]

Small cell lung cancer (SCLC) is highly aggressive and often relapses after initial treatment, leading to poor survival rates, highlighting the need for new therapeutic strategies.

Recent research has identified several molecular targets for SCLC, and new agents are being developed and tested in clinical trials to improve treatment outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapies in small cell lung cancer: a review. Abidin, AZ., Garassino, MC., Califano, R., et al.[2021]

A phase I trial presented in 2015 indicates that rovalpituzumab tesirine, an experimental antibody-drug conjugate, shows potential effectiveness against recurrent small cell lung cancer, a type of cancer with limited treatment options.

This trial highlights the promise of rovalpituzumab tesirine as a new therapeutic approach for patients suffering from this challenging form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ADC Shows Effectiveness in SCLC. [2015]

SU5416 effectively inhibited the growth of small cell lung cancer (SCLC) tumors in vivo, reducing tumor growth by at least 70% over a 3-week treatment period, and was as effective as carboplatin in certain chemotherapy-resistant models.

The drug works by blocking both tumor cell proliferation and angiogenesis, notably reducing microvessel density by about 50% and decreasing VEGF expression, highlighting its potential as a dual-action treatment for SCLC and other cancers expressing Kit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The multi-targeted kinase inhibitor SU5416 inhibits small cell lung cancer growth and angiogenesis, in part by blocking Kit-mediated VEGF expression. Litz, J., Sakuntala Warshamana-Greene, G., Sulanke, G., et al.[2012]

Rovalpituzumab tesirine (Rova-T) shows modest efficacy in treating extensively-stage small-cell lung cancer (SCLC) with a 12.4% objective response rate among 339 patients, indicating limited effectiveness in the third-line and beyond setting.

The treatment is associated with significant adverse events, with 63% of patients experiencing grade 3-5 toxicities, including fatigue and pleural effusion, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Rovalpituzumab Tesirine in Third-Line and Beyond Patients with DLL3-Expressing, Relapsed/Refractory Small-Cell Lung Cancer: Results From the Phase II TRINITY Study. Morgensztern, D., Besse, B., Greillier, L., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05619744

NCT05619744 | A Study to Evaluate Safety, Tolerability ... A Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-tumor Activity of RO7616789 in Advanced Small Cell Lung ...

2. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/lung-cancer/a-study-to-evaluate-safety--tolerability--pharmacokinet-04290.html

Clinical trial for Neuroendocrine Carcinoma, Small Cell L... This clinical trial aims to test the safety of RO7616789 and how well it works in people with SCLC and other NECs at different doses.

3. trialx.com trialx.com/clinical-trials/listings/265582/a-study-to-evaluate-safety-tolerability-pharmacokinetics-pharmacodynamics-and-preliminary-anti-tumor-activity-of-ro7616789-in-advanced-small-cell-lung-cancer-and-other-neuroendocrine-carcinomas/

Small Cell Lung Cancer ) ( NCT05619744 ) The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of RO ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12149116/

Harnessing delta-like ligand 3: bridging biomarker ... This review aims to synthesize recent advances in DLL3-targeted strategies, bridging biomarker-driven diagnostics to next-generation immunotherapies.

5. pharmacytimes.com pharmacytimes.com/view/targeting-dll3-in-small-cell-lung-cancer-and-other-neuroendocrine-carcinomas

Targeting DLL3 in Small Cell Lung Cancer and Other ... Recent therapeutic advances, such as the addition of immune checkpoint inhibitors to first-line treatment, have marginally improved outcomes, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11222730/

A promising target against small cell lung cancer This commentary highlighted the current knowledge about novel DLL3‐targeting agents for refractory small cell lung cancer.

7. ascopubs.org ascopubs.org/doi/10.1200/EDBK-25-472794

Taking a Bite Out of Small Cell Lung Cancer By Leveraging ... This review explores the rationale behind targeting DLL3, clinical data supporting tarlatamab's use, and emerging strategies to safely implement ...