Daratumumab for Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
Overseen bySally Lau
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: NYU Langone Health
Must not be taking: Antibiotics, Corticosteroids, Montelukast
Disqualifiers: Uncontrolled hypertension, Diabetes, COPD, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 Jurisdictions
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.
12345How 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.
23678Eligibility 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.
+5 more
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.
+14 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Patients with STK11/LKB1-Mutated NSCLCExperimental Treatment3 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
NYU Langone HealthNew York, NY
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Who Is Running the Clinical Trial?
NYU Langone HealthLead Sponsor
References
Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. [2022]Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma.
Daratumumab: First Global Approval. [2018]Daratumumab (Darzalex™) is a first-in-class, humanized IgG1κ monoclonal antibody that targets the CD38 epitope and was developed by Janssen Biotech and Genmab. Intravenous daratumumab was recently approved via an accelerated approval programme in the USA for patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent. The drug is in preregistration for this indication in the EU and Canada. In a phase II trial in patients with previously treated (as described above) relapsed or refractory multiple myeloma, monotherapy with daratumumab 16 mg/kg achieved an overall response rate of approximately 30 %. This article summarizes the milestones in the development of daratumumab leading to this first approval for multiple myeloma.
Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. [2018]Intravenous daratumumab (DARZALEX®) is a first-in-class human IgG1κ monoclonal antibody against CD38 available for use in patients with relapsed and/or refractory multiple myeloma. In phase I/II and II trials and a pooled analysis of these studies, daratumumab monotherapy induced an overall response (partial response or better) in approximately one-third of patients; responses were rapid, deep and durable. An overall survival (OS) benefit was seen with daratumumab monotherapy, including in patients with a minimal response or stable disease. In phase III trials, daratumumab in combination with either bortezomib plus dexamethasone or lenalidomide plus dexamethasone significantly prolonged progression-free survival and induced deep and durable responses compared with bortezomib plus dexamethasone or lenalidomide plus dexamethasone. An OS benefit with daratumumab triple combination therapy is yet to be demonstrated (as the OS data were not mature at the time of the last analysis). Daratumumab was generally well tolerated when used as monotherapy and had a generally manageable tolerability profile when used in combination therapy. Infusion-related reactions (IRRs) were the most common adverse events; these were predominantly grade 1 or 2 and mostly occurred during the first infusion. The most common grade 3-4 adverse events associated with daratumumab triple combination therapy were thrombocytopenia, neutropenia and anaemia. Although final OS data are awaited, current evidence indicates that daratumumab is a valuable addition to the treatment options currently available for patients with relapsed or refractory multiple myeloma.
Deep sustained response to daratumumab monotherapy associated with T-cell expansion in triple refractory myeloma. [2022]Daratumumab, a human CD38 monoclonal antibody that has direct on-tumor and immunomodulatory mechanisms of action, demonstrated clinical benefit as monotherapy or in combination with established regimens in patients with multiple myeloma with one or more prior lines of therapy.
The real-world outcomes of multiple myeloma patients treated with daratumumab. [2021]Most patients cannot be included in randomized clinical trials. We report real-world outcomes of all Danish patients with multiple myeloma (MM) treated with daratumumab-based regimens until 1 January 2019.
EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma. [2020]On May 20, 2016, a conditional marketing authorization valid through the European Union (EU) was issued for daratumumab as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) and who had demonstrated disease progression on the last therapy. The review of daratumumab was conducted under the EMA's accelerated assessment program for drugs that are of major interest for public health, especially from the point of view of therapeutic innovation.Daratumumab monotherapy achieved an overall response rate of 29.2% (95% confidence interval [CI] 20.8 to 38.9) in patients with multiple myeloma who had received at least three prior lines of therapy (including a PI and IMiD) or were double refractory to a PI and an IMiD (Study MMY2002). In patients with multiple myeloma relapsed from or refractory to two or more different prior therapies, including IMiDs (e.g., thalidomide, lenalidomide) and PI, an overall response was observed in 15 patients (35.7%, 95% CI: 21.6 to 52.0) (Study GEN501).On April 28, 2017, the therapeutic indication was extended to include the use of daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. This was based on two subsequent phase III studies of daratumumab in combination with lenalidomide/low-dose dexamethasone (MMY3003) and bortezomib/low dose dexamethasone (MMY3004).The most common side effects (grade 3-4) associated with daratumumab included neutropenia (37%), thrombocytopenia (23%), anemia (16%), pneumonia (10%), lymphopenia (8%), infusion-related reactions (6%), upper respiratory tract infection (5%), and fatigue (5%).The objective of this study was to summarize the scientific review done by the CHMP of the application leading to regulatory approval in the EU. The full scientific assessment report and product information, including the Summary of Product Characteristics (SmPC), are available on the EMA website (www.ema.europa.eu).
Daratumumab: monoclonal antibody therapy to treat multiple myeloma. [2018]Daratumumab (Darzalex[TM]) is a human monoclonal antibody (MAb) that targets CD38; a surface protein highly expressed across multiple myeloma (MM) cells. Preclinical studies have shown daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis upon secondary crosslinking and immunomodulatory effects via a decrease in immune suppressive cells. Daratumumab has a favorable toxicity profile and encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) and stem cell transplant have already failed. Given the encouraging efficacy and acceptable safety profile, daratumumab has emerged as a novel treatment option for MM both as a monotherapy and in combination with conventional and novel anti-MM agents. This review will focus on preclinical pharmacology, pharmacokinetics, safety and clinical development of daratumumab in MM.
Daratumumab monotherapy compared with historical control data in heavily pretreated and highly refractory patients with multiple myeloma: An adjusted treatment comparison. [2021]Daratumumab is a human CD38-directed monoclonal antibody approved in the United States as monotherapy for patients with multiple myeloma (MM) who have received ≥3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD, and in combination with lenalidomide/dexamethasone or bortezomib/dexamethasone for patients with MM who have received ≥1 prior LOT. This study compared the efficacy of daratumumab monotherapy versus historical controls through adjusted treatment comparison. Patient-level data were pooled from two daratumumab monotherapy studies (16 mg/kg; GEN501 and SIRIUS) and two independent US databases (IMS LifeLink and OPTUM), which reflect treatments used in real-world patients with MM who received ≥3 prior LOTs or were double refractory to a PI and an IMiD. Using a multivariate proportional hazards regression model, the relative treatment effect of daratumumab versus historical controls was estimated, adjusting for imbalances in characteristics between cohorts. Baseline characteristics that differed between patients treated with daratumumab (N = 148) and historical control (N = 658) were prior treatment with pomalidomide (55% vs 15%) or carfilzomib (41% vs 28%) and triple/quadruple refractory status (64% vs 14%). The adjusted overall survival-hazard ratio (OS-HR) for daratumumab versus historical control was 0.33 (95% confidence interval, 0.24-0.46) compared with 0.46 (0.35-0.59) for unadjusted HR. Impact of adjustment was mainly driven by refractory status and prior pomalidomide/carfilzomib exposure. This adjusted treatment comparison suggests that daratumumab demonstrates improved OS compared with historical control data in heavily pretreated and highly refractory MM patients.