RO7616789 for Small Cell Lung Cancer

Recruiting at 27 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

41 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called RO7616789 to see if it is safe and effective for people with severe lung cancer and neuroendocrine carcinoma. The study will look at how the drug moves through the body and its effects on cancer cells.

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.

What data supports the effectiveness of the drug RO7616789 for small cell lung cancer?

Research shows that rovalpituzumab tesirine, a component of RO7616789, has shown promise in treating small cell lung cancer, particularly in patients who have already undergone other treatments. It targets a specific protein found in these cancer cells, potentially making it effective in slowing down or stopping cancer growth. ^{1 2 3 4 5}

What data supports the effectiveness of the drug RO7616789 for small cell lung cancer?

Research shows that rovalpituzumab tesirine, a component of RO7616789, has shown promise in treating small cell lung cancer by targeting a specific protein (DLL3) found in these cancer cells. This drug has been effective in patients who have already undergone other treatments, suggesting it could be a valuable option for those with resistant forms of the disease. ^{1 2 3 4 5}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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

Findings from Research

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]

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]

References

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

ADC Shows Effectiveness in SCLC. [2015]

2. Ireland 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. [2012]

3. United States 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Targeted therapies in small cell lung cancer: a review. [2021]