Substudy to test investigational agents in combination with pembrolizumab in patients with PD (L)1 refractory NSCLC in a rolling-arm desig
- Conditions
- on-small cell lung cancerMedDRA version: 21.1Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOSSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-001629-29-PL
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 90
1. Participant has histologically- or cytologically-confirmed diagnosis of Stage IV (M1a, M1b, or M1c per current AJCC criteria) squamous or nonsquamous NSCLC
2. Participant with nonsquamous NSCLC who is not eligible for an approved targeted therapy
3. Have confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy (documentation of absence of tumor activating EGFR AND absence of ALK or ROS1 gene rearrangements). If participant’s tumor is known to have a predominantly squamous histology, molecular testing for EGFR mutation and ALK and ROS1 translocations will not be required, as this is not part of current diagnostic guidelines
4. Participant has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology assessment. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions
5. Participant is able to provide archival tumor tissue sample collected either within 5 years or within the interval from completion of last treatment but before entering the screening period; or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated obtained within 90 days of treatment initiation. FFPE tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Biopsies obtained before receipt of adjuvant/neoadjuvant chemotherapy will be permitted if recent biopsy is not feasible.
6. Participants must have progressed on treatment with an anti-PD-(L)1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. Anti-PD-(L)1 treatment progression is defined by meeting all the following criteria:
- Has received at least 2 doses of an anti-PD-(L)1 mAb.
- Has demonstrated PD after an anti-PD-(L)1 mAb as defined by RECIST 1.1.
- PD has been documented within 12 weeks from the last dose of an anti-PD-(L)1 mAb.
- Patients must have received exactly one line of prior anti-PD-1 or anti-PD-L1 therapy, either alone or in combination with platinum-based chemotherapy. Patients must have experienced disease progression during or after this regimen. Patients who receive front-line anti-PD-1 or anti-PD-L1 monotherapy as front-line treatment must have received a platinum-based chemotherapy, and must have also experienced
7. Have PD during/after platinum doublet chemotherapy
8. Participant is Male or Female who is at least 18 years of age at the time of providing documented the informed consent
9. Participant has an ECOG performance status of either 0 or 1 as assessed within 7 days before initiation of study intervention
10. Participant is able to complete all screening procedures within the 35-day screening window. A participant may be rescreened after sponsor consultation
11. Participant has adequate organ function; all screening laboratory tests should be performed within 10 days of initiation of study intervention
12. A male participant must agree to use contraception and should refrain from donating sperm for at least 120 days after study interventions
13. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
a. Not a WOCBP
OR
b. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after study intervention
14. The participant (or legally acceptable representative if applicable) has provided document
1. Has a diagnosis of small cell lung cancer. For mixed tumors, if small cell elements are present, the patient is ineligible
2. 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 before the first dose of study drug. Participants with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study
3. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
4. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 2 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days before first dose of study intervention. Patients having untreated brain metastases will require treatment of the metastases to be eligible to enter the study.
5. Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
6. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Lymphangitic spread of the NSCLC is not exclusionary
7. Has an active infection requiring systemic therapy
8. Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted
9. Has a known history of HIV infection (known HIV 1/2 antibodies positive)
10. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
11. Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
12. Has had major surgery (<3 weeks before first dose)
13. Is expected to require any other form of antineoplastic therapy while on study
14. Has received prior radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study intervention. Participants must have recovered from all radiationrelated toxicities, not require corticosteroids, and not have radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy to CNS disease)
15. Has received a live vaccine within 30 days before the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist® , MedImmune) are live attenuated vaccine
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1. To estimate the objective response rate (ORR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1);Secondary Objective: 1. To estimate Progression-Free Survival (PFS) as assessed by the investigator according to RECIST 1.1<br><br>2. To evaluate the safety and tolerability of investigational treatment combinations based on proportion of adverse events;Primary end point(s): 1. Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1);Timepoint(s) of evaluation of this end point: 1. Up to approximately 24 months
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)<br>2. Number of Participants Who Experience One or More Adverse Events (AEs)<br>3. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE);Timepoint(s) of evaluation of this end point: 1. Up to approximately 24 months <br>2. Up to approximately 27 months <br>3. Up to approximately 24 months