Daratumumab in STK11 Mutated NSCLC

NCT05807048 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 22-01512
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer With STK11/LKB1 Mutation

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) based on RECIST 1.1 Criteria

  ORR is the percentage of patients who best response recorded from study enrollment until disease progression is a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, where: CR = disappearance of all target lesions; and PR = at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Up to Month 24

Secondary Outcomes (9)

• Number of Adverse Events

  Up to Month 24

• Number of Severe Adverse Events

  Up to Month 24

• Number of Adverse Events Attributed to Study Drugs

  Up to Month 24

• Percent of Participants who Experience Complete Response (CR)

  Up to Month 24

• Percent of Participants who Experience Partial Response (CR)

  Up to Month 24

Study Arms (1)

Patients with STK11/LKB1-Mutated NSCLC

EXPERIMENTAL

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.

Drug: Daratumumab and Hyaluronidase-fihj; Drug: Pre-Intervention Medication; Drug: Post-Intervention Medication

Interventions

Daratumumab and Hyaluronidase-fihj DRUG

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) injection for subcutaneous use. Supplied as individually packaged single-dose vials providing 1,800 mg of daratumumab and 30,000 units of hyaluronidase per 15 mL.

Also known as: DARZALEX FASPRO

Patients with STK11/LKB1-Mutated NSCLC

Pre-Intervention Medication DRUG

The following pre-medications will be administered 1-3 hours before each dose of DARZALEX FASPRO: * Acetaminophen 650 to 1,000 mg orally * Diphenhydramine 25 to 50 mg (or equivalent) orally or intravenously * Montelukast 10mg PO prior to DARZALEX FASPRO®. * Methylprednisolone 100 mg (or equivalent) orally or intravenously

Patients with STK11/LKB1-Mutated NSCLC

Post-Intervention Medication DRUG

The following post-medications will be administered: * Methylprednisolone 20 mg (or an equivalent dose of an intermediate- or long acting corticosteroid) orally for 2 days starting the day after the administration of DARZALEX FASPRO®. * Patients with a history of chronic obstructive pulmonary disease will be prescribed short and long-acting bronchodilators and inhaled corticosteroids. * Antiviral prophylaxis for herpes zoster reactivation must be initiated within one week of daratumumab hyaluronidase-fihj administration and continued for 3 months following the end of treatment.

Patients with STK11/LKB1-Mutated NSCLC

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be ≥ 18 years of age and satisfy the legal age of consent in the jurisdiction in which the study is being conducted.
• Participant must have histologically or cytologically confirmed NSCLC that is metastatic or unresectable.
• Participants must have either progressed after prior immunotherapy with a PD-(L)1 inhibitor, platinum doublet chemotherapy and standard of care targeted therapy (if presence of an activating mutation is identified) for metastatic disease, be ineligible for, or have refused all therapeutic options. In cases where participants refuse currently available therapeutic options, this must be documented in the study records.
• Participants must have previously identified STK11/LKB1 mutation (identified locally in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory \[or equivalent\])
• Participant must have organ and bone marrow function as follows:
• Hemoglobin ≥9 g/dL
• Absolute blood neutrophil count (ANC) ≥1.5 x 109 /L
• Platelets ≥75 x 109 /L
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 x upper limit of normal (ULN)
• Total bilirubin =1.5 x ULN; participants with Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits.
• Serum creatinine \<1.5 x ULN or if available, calculated or measured creatinine clearance; \>50 mL/min/1.73 m2
• Before enrollment, a woman must be either:
• Not of childbearing potential: postmenopausal (\>45 years of age with amenorrhea for at least 12 months); permanently sterilized (eg, bilateral tubal occlusion \[which includes tubal ligation procedures as consistent with local regulations\], hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy,
• Of childbearing potential and practicing a highly effective method(s) of birth control consistent with local regulations regarding the use of birth control methods for participants participating in clinical studies, described as follows: practicing true abstinence (when this is in line with the preferred and usual lifestyle of the participant), which is defined as refraining from heterosexual intercourse during the entire period of the study, including up to 6 months after the last dose of study drug is given; OR have a sole partner who is vasectomized; OR practicing 2 methods of contraception, including one highly effective method (ie, established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device \[IUD\] or intrauterine system \[IUS\]), AND, a second method, (eg, condom with spermicidal foam/gel/film/cream/suppository or occlusive cap \[diaphragm or cervical/vault caps\] with spermicidal foam/gel/film/cream/suppository).
• Note: If the childbearing potential changes after start of the study (eg, woman who is not heterosexually active becomes active, postmenopausal woman experiences menarche) the woman must begin a highly effective method of birth control, as described above.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Participant has uncontrolled inter-current illness, including but not limited to poorly controlled hypertension or diabetes, ongoing or active systemic infection (ie, has discontinued all antibiotics for at least one week prior to first dose of study drug), diagnosed or suspected viral infection (except for HIV), or psychiatric illness/social situation that would limit compliance with study requirements, including ability to self-care for anticipated toxicities (eg. rash or paronychia).
• Participants with medical conditions requiring chronic continuous oxygen therapy are excluded.
• Participants with a history of chronic obstructive pulmonary disease (COPD) with grade ≥3 breathlessness on the modified medical research council (mMRC) dyspnea scale are excluded.
• Have known moderate or severe persistent asthma within the past 2 years, or current uncontrolled asthma of any classification.
• Participant has a history of clinically significant cardiovascular disease including, but not limited to:
• Prolonged QTcF interval \>480 msec or clinically significant cardiac arrhythmia or electrophysiologic disease (eg, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate). Note: Participants with cardiac pacemakers who are clinically stable are eligible.
• Uncontrolled (persistent) hypertension: systolic blood pressure \>180 mm Hg; diastolic blood pressure \>100 mm Hg
• Congestive heart failure defined as New York Heart Association (NYHA) class III-IV or Hospitalization for congestive heart failure (any NYHA class) within 6 months of study Day 1
• Pericarditis/clinically significant pericardial effusion
• Myocarditis
• Participant has had prior chemotherapy, targeted cancer therapy, or treatment with an investigational anti-cancer agent within 2 weeks or 4 half-lives, whichever is longer, before the first administration of study drug; or participant has received prior immunotherapy within 6 weeks before the first administration of study drug. For agents with long half-lives, the maximum required time since last dose is 4 weeks. Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less, (except for alopecia \[any grade\], Grade ≤2 peripheral neuropathy, and Grade \<2 hypothyroidism stable on hormone replacement). Autoimmune toxicities from previous immunotherapy must be fully resolved to baseline levels.
• Localized, radiotherapy for palliative purposes must be completed at least 7 days prior to treatment with daratumumab and hyaluronidase.
• Participants with untreated brain metastases. Participants with locally treated metastases that are clinically stable and asymptomatic for at least 2 weeks and who are off or receiving low-dose corticosteroid treatment (≤10 mg prednisone or equivalent) for at least 2 weeks prior to study treatment are eligible.
• Participant has leptomeningeal disease.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Interventions

daratumumab

Study Officials

• Salman Punekar

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: April 10, 2023
• Study Start: June 1, 2023
• Primary Completion: November 11, 2025
• Study Completion: November 11, 2025
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data will be granted upon reasonable request. Requests should be directed to sally.lau@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)