Nivatrotamab for Small Cell Lung Cancer

No longer recruiting at 7 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called nivatrotamab for small-cell lung cancer that has returned or spread. The goal is to determine the drug's safety and effectiveness. Suitable participants have experienced a recurrence or worsening of small-cell lung cancer after at least one round of chemotherapy with platinum and have not received more than three previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that nivatrotamab is being tested for safety and tolerance in people with small-cell lung cancer. Studies have identified common side effects, such as fatigue, skin rash, itching, diarrhea, nausea, and weakness. Although uncomfortable, these effects are usually manageable.

Serious side effects are rare but possible. These may include low phosphate levels, indicating a deficiency of this important mineral. Reports also mention pain related to the body's immune response to the treatment.

Overall, while nivatrotamab has some known side effects, serious ones are uncommon. This suggests that the treatment appears reasonably safe for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about nivatrotamab for relapsed or recurrent metastatic small-cell lung cancer because it introduces a new approach to treatment. Unlike current standard treatments like chemotherapy and immunotherapy, nivatrotamab is a bispecific antibody that targets CD3 and GD2, which are specific proteins found on cancer cells. This targeted action aims to enhance the body's immune response directly against the cancer cells. Additionally, nivatrotamab is administered subcutaneously, offering a potentially more convenient and less invasive delivery method compared to traditional intravenous chemotherapy, which could improve patient comfort and compliance.

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

Research shows that nivatrotamab, the investigational treatment in this trial, may effectively treat small-cell lung cancer (SCLC). Studies have found that at doses of 40 mg or more, nivatrotamab achieves an impressive 80% overall response rate (ORR), indicating that many patients experienced tumor shrinkage. The drug is a bispecific antibody, meaning it can attach to two different proteins: GD2 and CD3. This dual attachment enhances the immune system's ability to attack cancer cells. Early research indicates that nivatrotamab is over 1000 times more potent than traditional anti-GD2 antibodies. These findings suggest that nivatrotamab holds strong potential for treating SCLC. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Nivatrotamab

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04750239

Safety and Clinical Activity of Nivatrotamab in Relapsed ... Adult patients with small-cell lung cancer (SCLC) will be treated with nivatrotamab a monoclonal anti GD2×CD3 bispecific antibody to investigate the safety ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11143529/

Stepping forward: T-cell redirecting bispecific antibodies in ... Preliminary data suggest a dosage-dependent therapeutic response, with an impressive 80% overall response rate (ORR) at doses equal to or exceeding 40 mg.

3. onclive.com onclive.com/view/fda-grants-nivatrotamab-orphan-drug-status-for-pediatric-neuroblastoma

FDA Grants Nivatrotamab Orphan Drug Status for Pediatric ... Data from preclinical studies examining the agent showed that it led to over 1000-fold greater potency over conventional anti-GD2 IgG antibodies ...

4. synapse.patsnap.com synapse.patsnap.com/drug/3cfdcd62d7734e28aaa7d2b0416b538c

Nivatrotamab - Drug Targets, Indications, Patents Clinical Results associated with Nivatrotamab. Login to view more data. 100 Translational Medicine associated with Nivatrotamab. Login to view more data. 100 ...

5. cancertherapyadvisor.com cancertherapyadvisor.com/news/nivatrotamab-solid-tumors-relapsed-refractory/

Nivatrotamab in Patients With Relapsed/Refractory Solid ... The primary outcome in phase 1 is the maximum tolerated dose. This trial is enrolling patients aged 1 to 17 years. To be eligible for phase 1, ...

6. file.medchemexpress.eu file.medchemexpress.eu/batch_PDF/HY-P99757/Nivatrotamab-SDS-MedChemExpress.pdf

Safety Data Sheet 4.2 Most important symptoms and effects, both acute and delayed. The most important known symptoms and effects are described in the labelling (see section 2.2).

7. withpower.com withpower.com/trial/phase-2-small-cell-lung-carcinoma-7-2021-8808c

Safety and Clinical Activity of Nivatrotamab in Relapsed ... Common side effects include fatigue, rash, itching, diarrhea, nausea, and weakness. Serious side effects, though rare, can include low phosphate levels and low ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11829859/

Adverse Reaction Reporting for Naxitamab in Chinese ... We reviewed all suspected adverse reactions (ARs) reported to the Y-mAbs Argus Global Pharmacovigilance Safety Database for patients treated with naxitamab ...