Lung Cancer
MK2870-019: Pembrolizumab With or Without MK-2870 in Resectable NSCLC not Achieving pCR
Description
A Phase 3 Randomized Open-Label Study of Adjuvant Pembrolizumab With or Without MK-2870 in Participants With Resectable Stage II to IIIB (N2) NSCLC not Achieving pCR After Receiving Neoadjuvant Pembrolizumab With Platinum-based Doublet Chemotherapy Followed by Surgery
Inclusion Notes
Inclusion Criteria
An individual is eligible for inclusion in the study if the individual meets all of the following criteria:
Type of Participant and Disease Characteristics
Criteria 1 through 5 apply to screening for the neoadjuvant and adjuvant periods:
1. Has histological or cytological confirmation of squamous or nonsquamous NSCLC, resectable clinical Stage II, IIIA or IIIB (with nodal involvement [N2]) per AJCC eighth edition guidelines (Appendix 8). No restaging is required at the time of randomization.
Note: Lymph node disease requires histological or cytological confirmation if it will affect stage grouping stratification, otherwise imaging can act as a surrogate for pathological staging. If a lymph node biopsy result is negative for malignancy but the investigator believes this result to be a false negative, then clinical staging is at the investigator’s discretion. If performing a lymph node biopsy is considered high risk or a lymph node is not readily accessible by minimally invasive techniques, then lymph node biopsy confirmation is not required.
2. Confirmation that either EGFR-directed or ALK-directed therapy is not indicated as primary therapy (historical data with respect to the index NSCLC under study of absence of tumor-activating EGFR mutations [eg, DEL19 or L858R] or ALK mutations, as determined by local laboratory).
Note: If participant’s tumor has a predominantly squamous histology, molecular testing for EGFR or ALK mutation is not required.
3. Able to undergo surgery based on opinion of investigator after consultation with surgeon.
4. Able to receive neoadjuvant pembrolizumab and platinum-based doublet chemotherapy.
Note: Participants with resectable NSCLC (Criterion 1) previously treated outside the study with 1 to 4 cycles of neoadjuvant pembrolizumab and platinum-based chemotherapy and who successfully completed surgery with surgical tumor tissue sample available, may advance to screening for the pre-randomization period (see Section 1.3.1 and Section 1.3.3). Refer to Section 8.1.8.2 regarding timing of surgery relative to first dose of neoadjuvant therapy.
5. An ECOG performance status of 0 to 1 assessed within 10 days before first dose of study treatment
Criteria 6 through 11 apply to screening for the adjuvant period only, before randomization:
6. Achieved R0 or R1 resection status.
7. Has not achieved pCR at surgery by local review of pathology. See Section 4.1 for definition of pCR.
8. Tumor tissue sample from surgical resection has been provided for determination of PD-L1 and TROP2 status by central vendor before randomization into the adjuvant period. Submission of additional tumor specimen from surgical resection may be required before randomization if initial tumor tissue submitted was not evaluable. Details pertaining to tumor tissue submission can be found in the Central Laboratory Manual.
9. Confirmed to be disease-free based on re-baseline radiological assessment as documented by contrast-enhanced chest/abdomen/pelvis CT (or MRI) within 28 days before randomization.
Note: Participants may not be randomized without BICR verification of disease-free status.
10. Is able to continue on adjuvant pembrolizumab.
11. An ECOG performance status of 0 to 1 assessed within 10 days before randomization.
All remaining inclusion criteria apply to screening for both the neoadjuvant and adjuvant periods. Demographics
12. Is an individual of any sex/gender, from at least 18 years of age at the time of providing the informed consent.
Assigned Male Sex at Birth
13. If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
- MK-2870: 120 days
- Pembrolizumab: no requirements
- Chemotherapy: 100 days
- Radiation therapy: 90 days
Refrains from donating sperm
PLUS either:
Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent
OR
Uses contraception as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview) as detailed below:
Uses a penile/external condom when having penile-vaginal intercourse with a nonparticipant of childbearing potential who is not currently pregnant PLUS partner use of an additional contraceptive method, as a condom may break or leak.
Note: Participants capable of producing ejaculate whose partner is pregnant or breastfeeding must agree to use a penile/external condom during each episode of sexual activity in which the partner is at risk of drug exposure via ejaculate.
Contraceptive use by participants capable of producing sperm should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.
Assigned Female Sex at Birth
14. A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:
Is not a POCBP
OR
Is a POCBP and:
Uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 5 during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The participant agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during this period for the purpose of reproduction. The length of time required to continue contraception for each study intervention is:
- MK-2870: 210 days
- Pembrolizumab: 120 days
- Chemotherapy: 190 days
- Radiation therapy: 180 days
The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.
Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study intervention are in Section 8.3.6.
Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention.
Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy.
Additional Categories
16. Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement are eligible.
17. HIV-infected participants must have well controlled HIV on ART, defined as:
Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of screening
Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening
It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months
Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the study
The combination ART regimen must not contain any antiretroviral medications that interact with CYP3A4 inhibitors/inducers/substrates (https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers)
18. Adequate organ function as defined in the following table (Table 8). Specimens must be collected within 10 days before the start of study intervention.
19. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load at screening.
Note: Participants should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention.
Hepatitis B screening tests are not required unless:
- Known history of HBV infection
- As mandated by local health authority
20. Participants with history of HCV infection are eligible if HCV viral load is undetectable at least 4 weeks before the start of study intervention.
Note: Participants must have completed curative antiviral therapy at least 4 weeks before start of study intervention. Hepatitis C screening tests are not required unless:
- Known history of HCV infection
- As mandated by local health authority
Start Date
Tuesday, April 15, 2025
Principal / Contact Name
Leonard Henry, MD, MBA, FACS