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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests daratumumab, a medication, to determine its effectiveness in treating non-small cell lung cancer (NSCLC) that has spread and involves a specific genetic mutation called STK11/LKB1. The researchers aim to discover if daratumumab can slow or halt the cancer's progression, particularly in patients who have already undergone treatments like chemotherapy and immunotherapy. The study seeks participants with this specific type of lung cancer who have received prior treatments and possess the STK11/LKB1 mutation. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering hope for those seeking new options.

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.

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

Research has shown that daratumumab is generally safe in treatments. The FDA has already approved it for treating multiple myeloma, a type of blood cancer, indicating it is usually well-tolerated. In other studies, patients taking daratumumab reported few serious side effects.

For those with non-small cell lung cancer (NSCLC), early studies showed promising safety results, with no major safety concerns reported. Patients often found it more comfortable when the drug was administered as an injection under the skin rather than by other methods.

Overall, daratumumab's use in other treatments and its method of administration suggest it is generally safe for patients. However, individual reactions can vary, so discussing participation in a clinical trial with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for non-small cell lung cancer (NSCLC) that often involve chemotherapy and targeted therapies, daratumumab offers a unique approach by targeting a specific protein called CD38 on cancer cells. Researchers are particularly excited because daratumumab, combined with hyaluronidase, is administered subcutaneously, making it potentially less invasive and easier to receive than traditional intravenous therapies. Additionally, its targeted mechanism could offer a more precise attack on cancer cells, especially in patients with STK11/LKB1 mutations, potentially leading to better outcomes with fewer side effects.

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

Research has shown that daratumumab effectively treats multiple myeloma, a type of blood cancer, helping patients respond well to treatment. In this trial, researchers are testing daratumumab for non-small cell lung cancer (NSCLC) with a specific genetic change called STK11/LKB1. Participants will receive daratumumab, which targets and kills certain cancer cells, potentially slowing the disease. Although daratumumab is not yet proven for NSCLC, its success in other cancers offers hope for its effectiveness in this trial. ^{6 7 8 9 10}

Who Is on the Research Team?

Salman Punekar

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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

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

My organs and bone marrow are functioning well.

Before enrollment, a woman must meet specific criteria related to childbearing potential and contraception

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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]

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]

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]

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]

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]

Citations

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U.S. FDA Oncologic Drugs Advisory Committee votes in favor ... DARZALEX FASPRO® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a ...

2. jnj.com jnj.com/innovativemedicine/us/darzalex-faspro-daratumumab-and-hyaluronidase-fihj-based-regimens-demonstrate-improved-rates-of-minimal-residual-disease-mrd-negativity-and-progression-free-survival-in-patients-with-newly-diagnosed-multiple-myeloma

DARZALEX FASPRO® (daratumumab and hyaluronidase ... New analysis from Phase 3 CEPHEUS study demonstrates 85 percent of patients who achieved MRD negativity (10-6) with DARZALEX FASPRO® were ...

3. withpower.com withpower.com/trial/daratumumab-for-non-small-cell-lung-cancer-30e3b

Daratumumab for 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 ...

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Daratumumab in STK11 Mutated NSCLC - Carebox Connect This is a single-arm study of daratumumab in metastatic non-small cell lung cancer (NSCLC) patients with an STK11/LKB1 mutation.

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DARZALEX FASPRO® (daratumumab and hyaluronidase ... A DARZALEX FASPRO (daratumumab and hyaluronidase-fihj)-based quadruplet regimen demonstrated deep and sustained minimal residual disease (MRD) negativity rates.

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Daratumumab (Darzalex) and Daratumumab and ... “The administration of daratumumab was associated with a good safety profile and non ... non-small cell lung cancer (NSCLC). Pre-clinical studies indicated that ...

7. darzalex.com darzalex.com/dvrd/

DARZALEX & DARZALEX FASPRO® (daratumumab and ... An FDA-approved treatment combination for patients who are newly diagnosed with multiple myeloma and eligible to receive a stem cell transplant.

8. onclive.com onclive.com/view/teclistamab-plus-daratumumab-boosts-survival-in-r-r-myeloma

Teclistamab Plus Daratumumab Boosts Survival in R ... Teclistamab plus daratumumab improved progression-free and overall survival in relapsed/refractory multiple myeloma after 1 to 3 lines of ...

9. cancerletter.com cancerletter.com/clinical-roundup/20241213_9i/

Darzalex Faspro-based regimens demonstrate improved ... Darzalex Faspro-based regimens demonstrate improved rates of MRD negativity and PFS. December 13, 2024 · Vol.50 No.46.

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DARZALEX FASPRO® (daratumumab and hyaluronidase- ... Overall, results indicated that DARZALEX FASPRO patients were more satisfied with their cancer therapy and had more positive perceptions of ...