Safety and Clinical Activity of Nivatrotamab in Relapsed/Recurrent Metastatic Small-cell Lung Cancer

Recruiting at 6 trial locations

Overseen By Joris Wilms

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Y-mAbs Therapeutics

Must not be taking: Immunosuppressants, Anticonvulsants, Steroids

Disqualifiers: Active infections, Autoimmune diseases, Heart disease, others

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

Compensation: Varies

Number of Visits: Unknown

3 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any immunosuppressive medications and steroids at least 10 days before starting the study drug. If you are on any other investigational therapy, you must stop it 3 weeks before the trial begins.

What safety data exists for Nivatrotamab (also known as Nivolumab)?

Nivolumab, a treatment for various cancers, has been studied in many clinical trials. Common side effects include fatigue, rash, itching, diarrhea, nausea, and weakness. Serious side effects, though rare, can include low phosphate levels and low white blood cell counts. There is also a small risk of immune-related issues like colitis (inflammation of the colon). ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests nivatrotamab, a drug that helps the immune system attack small-cell lung cancer. It targets specific proteins on cancer and immune cells to help the body fight the cancer. The study aims to find the safest dose and see how well it works in patients.

Eligibility Criteria

Inclusion Criteria

Signed and dated informed consent has been provided prior to any trial-related procedures.

Patient willing and able to comply with the trial protocol

Histologically or cytologically proven SCLC. Radiographical relapse/progression after minimum 1 line of platinum-containing chemotherapy with PR or CR as the best response (only applicable for phase 2) and not more than 3 prior lines of therapy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase 1 dose escalation to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) using a modified Bayesian Optimal Interval Design (mBOIN). Dose-limiting toxicities (DLTs) are collected and assessed.

4 weeks

Multiple visits for dose administration and monitoring

Dose Expansion

Phase 2 dose expansion to assess long-term safety, tolerability, and clinical activity of nivatrotamab at the MTD/RP2D. Patients are stratified by platinum sensitivity.

Up to 26 weeks

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Nivatrotamab

Participant Groups

Group I: Nivatrotamab Experimental Treatment 1 Intervention

Subcutaneous administration of nivatrotamab up to 13 cycles

Who Is Running the Clinical Trial?

Y-mAbs Therapeutics

Lead Sponsor

Trials

26

Recruited

1,600+

Findings from Research

Nivolumab, an immune checkpoint inhibitor, shows a low rate of severe adverse effects (grade ≥3 AEs at 12%) and a very low mortality rate (0.25%), indicating it is a relatively safe treatment option for cancer patients.

In terms of efficacy, nivolumab demonstrates better treatment responses and survival rates compared to traditional chemotherapy, with a 1-year overall survival rate of 52% and a significantly higher objective response rate (ORR) of 26%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. Tie, Y., Ma, X., Zhu, C., et al.[2022]

In a meta-analysis of five studies involving 2399 patients, nivolumab was found to significantly lower the risk of hematological toxicities such as anemia, neutropenia, and leukopenia compared to other treatments.

The relative risks for these conditions were notably low, indicating that nivolumab may be a safer option regarding hematological side effects, which is important for clinicians when considering treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. Shi, Z., Liu, X., Chen, M., et al.[2023]

Nivolumab, an immunotherapy drug, can cause immune-mediated side effects like colitis, which may occur even after treatment has stopped.

Using higher doses of methylprednisolone led to a quicker resolution of symptoms in patients compared to previous cases, potentially reducing the need for hospitalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and immune-mediated colitis. Walker, H., Brennan, P., Groome, M., et al.[2023]

The combination of nivolumab and relatlimab shows a manageable safety profile for patients with advanced melanoma who have already undergone treatment.

This combination therapy may offer a new option for patients with pretreated melanoma, suggesting potential efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab Is Safe and Efficacious in Pretreated Melanoma. [2023]

The study confirms that PD-1 inhibitors like Pembrolizumab and Nivolumab improve response and survival rates in advanced melanoma patients, especially when combined with the CTLA-4 inhibitor Ipilimumab, which shows superior efficacy compared to monotherapies.

However, these immunotherapies are associated with significant immune-related adverse events, some of which can be life-threatening, highlighting the need for further studies to better understand their safety profiles and mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Public Adverse Event Data Insights into the Safety of Pembrolizumab in Melanoma Patients. Schaefer, A., Sachpekidis, C., Diella, F., et al.[2020]

References

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

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. [2022]

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

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Nivolumab and immune-mediated colitis. [2023]

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

Nivolumab Plus Relatlimab Is Safe and Efficacious in Pretreated Melanoma. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Public Adverse Event Data Insights into the Safety of Pembrolizumab in Melanoma Patients. [2020]