LUNAR2Trial

JRCT ID: jRCT2072240024

Registered date:21/06/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Subjects with metastatic NSCLC
• Date of first enrollment: 21/06/2024
• Target sample size: 734
• Countries of recruitment: America,Japan,Belgium,Japan,Czech,Japan,France,Japan,Germany,Japan,Hungary,Japan,Israel,Japan,Italy,Japan,Netherlands,Japan,Poland,Japan,Spain,Japan,Switzerland,Japan,Serbia,Japan,Koria,Japan,Singapore,Japan
• Study type: Interventional

Intervention(s)

Standard of care therapy will be provided according to tumor histology.
Non-squamous histology:
Induction treatment - 4 cycles every 3 weeks (q3w):
-Pembrolizumab 200 mg will be administered as an IV infusion over 30 minutes. Pembrolizumab will be administered prior to chemotherapy.
-Pemetrexed - 500 mg/m2 will be administered as an IV infusion over 10 minutes (supplementary folic acid, vitamin b12, and corticosteroid will be administered per prescribing information)
-Cisplatin - 75 mg/m2 of body surface area (BSA) will be administered as an IV infusion over 30 minutes or carboplatin - Area Under the Curve (AUC) -time, 5 mg/mL per minute be administered as an IV infusion over 3 hours
Maintenance treatment - up to a total of 35 cycles (including induction), q3w, same dose
-Pembrolizumab
-Pemetrexed - per the investigators discretion

Squamous histology:
Induction treatment- 4 cycles, q3w:
-Pembrolizumab 200 will be administered as an IV infusion over 30 minutes.
-Paclitaxel - 200 mg/m2 of BSA will be administered as an IV infusion over 3 hours, or nab-paclitaxel - 100 mg/m2 on days 1, 8 and 15 to be administered as an IV infusion over 30 minutes. Paclitaxel / nab-paclitaxel should be completely administered before initiating carboplatin dose.
-Carboplatin - AUC- time curve, 6 mg/mL per minute as an IV infusion over 15-60 minutes immediately after paclitaxel or nab-paclitaxel as per local practice and labels. The carboplatin dose should be calculated using Calvert formula. Carboplatin dose should not to exceed 900 mg
Maintenance treatment - up to a total of 35 cycles (including induction), q3w, same dose
-Pembrolizumab

Outcome(s)

Primary Outcome

Overall survival, in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy compared to OS of those treated with pembrolizumab and platinum-based chemotherapy alone.
Progression-Free Survival, per Response Evaluation Criteria in Solid Tumors RECIST 1.1 as assessed by Blinded Independent Central Review BICR, in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy compared to PFS of those treated with pembrolizumab and platinum-based chemotherapy alone.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. a. 22 years of age or older in the USA b. 18 years of age or older outside of the USA.
2.Histologically or cytologically diagnosis of stage 4 (according to Version 8 of the American Joint Committee on Cancer [AJCC] criteria) non-squamous or squamous NSCLC.
3.Evaluable (measurable or non-measurable) disease in the thorax per RECIST v1.1.
4.Have not received prior systemic treatment for their metastatic NSCLC. Subjects who received adjuvant, neoadjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic disease are eligible if the therapy was completed at least 12 months prior to the development of metastatic disease.
5.Have provided tumor tissue from locations not radiated prior to biopsy; formalin - fixed specimens after the subject has been diagnosed with metastatic disease will be preferred for determination of PD-L1 status assessed locally prior to randomization.
6.ECOG Performance Status (PS) of 0-1.
7.Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to randomization:
o ANC greater than or equal to 1.5 x 10^9/L (1500/microL) without granulocyte colony-stimulating factor support
o Platelet count greater than or equal to 100 x 10^9/L (100,000/microL) without transfusion
o Hemoglobin greater than or equal to 90 g/L (9 g/dL)
Subjects may be transfused to meet this criterion. In the case of a transfusion, the transfusion must be administered more than 24 hours prior to the administration of chemotherapy + pembrolizumab and a repeat complete blood count must meet the protocol criteria.
oAST, ALT less than or equal to 2.5 times ULN (less than or equal to 5 times ULN for participants with liver metastases)
o Serum bilirubin less than or equal to 1.5 times ULN
o Serum creatinine less than or equal to 1.5 times ULN
For subjects not receiving therapeutic anticoagulation: INR or aPTT less than or equal to 1.5 times ULN (unless participant is receiving anticoagulant therapy as long as INR or aPTT is within therapeutic range of intended use of anticoagulants).
8.A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
a.Not a woman of childbearing potential (WOCBP)
b.A WOCBP who agrees to use two adequate barrier methods or a barrier method plus a hormonal method during the treatment period and for at least 120 days after the last dose of study therapy. Such methods of contraception, or true abstinence from heterosexual activity, when this is in line with the preferred and usual lifestyle of the subject, are required (periodic abstinence, e.g., calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception).
9.If male subject with a female partner(s) of child-bearing potential, must agree to use an effective contraception method based on the recommendation of the investigator or a gynecologist, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
10.All subjects must sign written informed consent.
11.Able to operate the NovoTTF-200T system independently or with the help of a caregiver.

Exclude criteria

1.Mixed small cell and NSCLC histology.
2.EGR sensitizing mutation and/or ALK translocation, and/or ROS1 and/or RET targetable gene rearrangement, and/or METex14 skipping mutation, and/or NTRK1/2 gene fusion directed therapy is indicated or planned for other targeted therapy, where such testing and therapy is locally approved and available. Source documentation of the applicable driver mutations should be available at the site. Note: For subjects enrolled who are known to have a tumor of predominantly squamous histology, molecular testing for EGFR mutation, ALK translocation and ROS1 and/or RET gene rearrangements, and/or METex14 skipping mutation, and/or NTRK1/2 gene fusion will not be required as this is not standard of care and is not part of current diagnostic guidelines.
3.Has received systemic therapy for metastatic disease.
4.Had major surgery <3 weeks prior to randomization
5.Received radiation therapy to the lung that is > 30 Gy within 6 months of randomization.
6. Has received prior radiotherapy within two weeks of randomization. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A one-week washout is permitted for palliative radiation (less than or equal to two weeks of radiotherapy) to non-CNS disease.
7.Is expected to require any other form of antineoplastic therapy while on study.
8.Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
Note: Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
9.Has untreated or symptomatic Central Nervous System (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they were treated before randomization and are clinically stable and without requirement of steroid treatment for at least 3 days prior to randomization.
10.Has active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
11.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior randomization. Subjects with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study.
12.Had prior treatment with any other anti-PD-1, or PD-L1 or PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors or mechanisms in the 12 months prior to randomization. Examples of such antibodies include (but are not limited to) antibodies against IDO, PD-L1, IL-2R, GITR.
13.Participation in another clinical study with an investigational agent or device during the 4 weeks prior to randomization.
Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
14.Concurrent treatment with other experimental treatments for NSCLC while in the study.
15.Significant comorbidity which is expected to affect the subjects prognosis or ability to receive the study therapy:
a) History of significant cardiovascular disease unless the disease is well controlled.
Significant cardiac disease includes second/third-degree heart block; significant ischemic heart disease; poorly controlled hypertension; congestive heart failure of the New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary activity results in fatigue, palpitation or dyspnea).
b) History of arrhythmia that is symptomatic or requires treatment. Subjects with atrial fibrillation or flutter controlled by medication are not excluded from participation in the study.
c) Any serious underlying medical condition (including active infection, e.g. hepatitis C [defined as positive RNA viral load], or active hepatitis B defined as positive HbsAg) that would impair the ability of the subject to receive protocol therapy.
d) History of any psychiatric condition that might impair the subjects ability to understand or comply with the requirements of the study or to provide consent.
e) Known medical condition that, in the investigators opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
f) In Japan, subjects with pre-existing or complicated interstitial lung diseases (including idiopathic interstitial pneumonia, radiation pneumonitis, drug-induced interstitial lung disease, etc.) are excluded.
16.Implanted pacemaker, defibrillator, or other electrical medical devices in the torso.
17.Known allergies or hypersensitivity to medical adhesives, hydrogel.
18.Has a known sensitivity to any component of the planned systemic therapies (pembrolizumab, cisplatin/carboplatin, pemetrexed/paclitaxel/nab-paclitaxel).
19.Pregnant or breastfeeding (all subjects of childbearing potential must use effective contraception method based on the recommendation of the investigator or a gynecologist for up to 120 days after the last dose of pembrolizumab and through 180 days after last dose of chemotherapy).
20.Admitted to an institution by administrative or court order.
21.Any medical contraindication to treatment with platinum-based doublet chemotherapy or pembrolizumab as listed in the local labelling.

Related Information

• Primary Sponsor: Azuma Hisaya