Daratumumab for Non-Small Cell Lung Cancer

Overseen By Salman Punekar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must not be taking: Antibiotics, Corticosteroids, Montelukast

Disqualifiers: Uncontrolled hypertension, Diabetes, COPD, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Until disease progression

14 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single-arm study of daratumumab in metastatic non-small cell lung cancer (NSCLC) patients with an STK11/LKB1 mutation. Patients will have received previous standard of care treatment including chemotherapy, immunotherapy and targeted therapy. Patients will be treated with the standard subcutaneous dosing of daratumumab (weekly for 8 administrations, then every 2 weeks for 8 administrations then every 4 weeks until progression). All follow-up visits and imaging will be performed as per standard of care. This is a signal finding study and an overall response rate ≥20% is considered clinically meaningful.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not have had chemotherapy, targeted cancer therapy, or investigational anti-cancer agents within 2 weeks before starting the study drug. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug Daratumumab for treating non-small cell lung cancer?

Daratumumab has shown effectiveness in treating multiple myeloma, a type of blood cancer, by helping patients achieve a significant response to treatment. While this data is specific to multiple myeloma, it suggests that Daratumumab has potential as a cancer treatment due to its ability to target cancer cells. ^{1 2 3 4 5}

How is the drug Daratumumab unique for treating non-small cell lung cancer?

Daratumumab is unique because it is a monoclonal antibody that targets the CD38 protein, which is not a common target in non-small cell lung cancer treatments. It has been primarily used for multiple myeloma, where it works by helping the immune system attack cancer cells, and its application to lung cancer represents a novel approach. ^{2 3 6 7 8}

Research Team

Salman Punekar

Principal Investigator

NYU Langone Health

Eligibility Criteria

Adults with metastatic or unresectable NSCLC and an STK11/LKB1 mutation, who have tried standard treatments like chemo, immunotherapy, and targeted therapy. They must be in good physical condition (ECOG 0-1), not pregnant or breastfeeding, able to consent, and meet specific health criteria. Excluded are those with significant heart disease, continuous oxygen needs, untreated brain metastases, other active cancers requiring treatment within the last 2 years.

Inclusion Criteria

I am 18 years or older and legally able to consent.

My lung cancer is confirmed and cannot be removed by surgery.

My organs and bone marrow are functioning well.

Exclusion Criteria

I have severe breathlessness due to COPD.

I have a history of serious heart problems.

I have had cancer treatment within the specified timeframes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab subcutaneously: weekly for 8 administrations, then every 2 weeks for 8 administrations, then every 4 weeks until progression

Until disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

Treatment Details

Interventions

• Daratumumab

Trial Overview The trial is testing daratumumab's effectiveness for NSCLC patients with an STK11 mutation after previous treatments failed. It involves a single-arm study where all participants receive daratumumab at regular intervals until their disease progresses while being monitored as per usual care standards.

Participant Groups

Group I: Patients with STK11/LKB1-Mutated NSCLC Experimental Treatment 3 Interventions

Participants will receive daratumumab 1800mg and hyaluronidase 30,000 units (combined product DARZALEX Faspro) administered subcutaneously per the following dosing schedule: * Once per week for 8 administrations (Week 1-8) * Once every two weeks for 8 administrations (Week 9-16) * Once every 4 weeks until disease progression or unacceptable toxicity.

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

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Findings from Research

In a phase 3 trial with 569 patients, the addition of daratumumab to lenalidomide and dexamethasone significantly improved progression-free survival, with only 18.5% of patients experiencing disease progression compared to 41.0% in the control group.

Daratumumab also resulted in a higher overall response rate (92.9% vs. 76.4%) and a greater percentage of patients achieving minimal residual disease status (22.4% vs. 4.6%), although it was associated with a higher incidence of neutropenia and infusion-related reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. Dimopoulos, MA., Oriol, A., Nahi, H., et al.[2022]

Daratumumab, a monoclonal antibody targeting CD38, has been approved in the USA for treating multiple myeloma in patients who have undergone at least three prior therapies, demonstrating its role as a treatment option for difficult-to-treat cases.

In a phase II trial, daratumumab monotherapy showed an overall response rate of about 30% in patients with relapsed or refractory multiple myeloma, indicating its efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: First Global Approval. McKeage, K.[2018]

Daratumumab, a monoclonal antibody targeting CD38, has shown significant efficacy as a monotherapy in relapsed/refractory multiple myeloma, achieving an overall response in about one-third of patients, with rapid and durable effects.

In combination with other treatments like bortezomib or lenalidomide, daratumumab significantly prolonged progression-free survival, although the overall survival benefit is still being evaluated, and it was generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Blair, HA.[2018]

A 70-year-old patient with advanced multiple myeloma, who had previously undergone five lines of therapy, achieved a stringent complete response and over 3.5 years of remission with daratumumab monotherapy, significantly exceeding the median response duration of 7.6 months for similar patients.

The patient's treatment with daratumumab led to notable changes in his immune profile, including expansion of CD8+ T-cells and a decrease in regulatory T-cells, indicating a strong adaptive immune response that supports the drug's immunomodulatory effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep sustained response to daratumumab monotherapy associated with T-cell expansion in triple refractory myeloma. Usmani, SZ., Khan, I., Chiu, C., et al.[2022]

In a study of 635 Danish patients with multiple myeloma treated with daratumumab, the overall response rate was highest (80.5%) when daratumumab was combined with immunomodulatory drugs (IMiDs) and administered early in the treatment sequence, leading to a median time to next treatment of 16.1 months.

Patients with high-risk genetic abnormalities (like t(4;14), t(14;16), or del17p) experienced worse outcomes, while those with amplification of 1q had outcomes similar to standard-risk patients, highlighting the importance of genetic factors in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The real-world outcomes of multiple myeloma patients treated with daratumumab. Szabo, AG., Klausen, TW., Levring, MB., et al.[2021]

Daratumumab received conditional marketing authorization in the EU for treating relapsed and refractory multiple myeloma, showing an overall response rate of 29.2% in heavily pre-treated patients, indicating its efficacy as a monotherapy.

The drug was later approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone, demonstrating improved progression-free survival in patients who had received at least one prior therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma. Tzogani, K., Penninga, E., Schougaard Christiansen, ML., et al.[2020]

Daratumumab is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

Daratumumab, a monoclonal antibody targeting CD38, shows significantly improved overall survival in patients with multiple myeloma who have undergone extensive prior treatments, with an adjusted overall survival-hazard ratio of 0.33 based on a study of 148 patients compared to historical controls.

The study highlights that daratumumab is particularly effective in heavily pretreated patients, including those who are triple or quadruple refractory to other therapies, indicating its potential as a critical treatment option in advanced multiple myeloma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab monotherapy compared with historical control data in heavily pretreated and highly refractory patients with multiple myeloma: An adjusted treatment comparison. Usmani, SZ., Diels, J., Ito, T., et al.[2021]

References

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

Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Daratumumab: First Global Approval. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. [2018]

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

Deep sustained response to daratumumab monotherapy associated with T-cell expansion in triple refractory myeloma. [2022]

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

The real-world outcomes of multiple myeloma patients treated with daratumumab. [2021]

6. England pubmed.ncbi.nlm.nih.gov

EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma. [2020]

7. Spain pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. [2018]

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

Daratumumab monotherapy compared with historical control data in heavily pretreated and highly refractory patients with multiple myeloma: An adjusted treatment comparison. [2021]