Clinical Trial 23182

• Overview

  Study Title:

  A Phase 3, Randomized, Double-blind, Placebo- and Active-Comparator-Controlled Clinical Study of Adjuvant V940 (mRNA-4157) Plus Pembrolizumab Versus Adjuvant Placebo Plus Pembrolizumab in Participants With Resected Stage II, IIIA, IIIB (N2) Non-small Cell Lung Cancer

  Summary:

  The goal of this study is to evaluate intismeran autogene plus pembrolizumab versus placebo plus pembrolizumab for the adjuvant treatment of margin negative, completely resected Stage II, IIIA, IIIB (with nodal involvement [N2]) non-small cell lung cancer (NSCLC). The primary hypothesis is that intismeran autogene plus pembrolizumab is superior to placebo plus pembrolizumab with respect to disease-free survival (DFS) as assessed by the investigator.

  Objective:

  Primary * To compare V940 plus pembrolizumab to placebo plus pembrolizumab with respect to DFS. Secondary * To compare V940 plus pembrolizumab to placebo plus pembrolizumab with respect to OS. * To evaluate V940 plus pembrolizumab to placebo plus pembrolizumab with respect to DMFS as assessed by the investigator. * To evaluate V940 plus pembrolizumab to placebo plus pembrolizumab with respect to LCSS. * To evaluate V940 plus pembrolizumab to placebo plus pembrolizumab with respect to mean change from baseline in global health status/QoL, physical functioning, and role functioning using the EORTC QLQ-C30 and EORTC QLQ-LC24. * To evaluate the safety and tolerability of V940 plus pembrolizumab.

• Treatments

  Therapies:

  Immunotherapy

  Medications:

  Pembrolizumab (Keytruda); Placebo (); V940 ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Has undergone margin negative, completely resected NSCLC, and has pathological Stage II, IIIA, IIIB (N2) squamous or nonsquamous TNM staging per AJCC Eighth Edition . See protocol for preferred/recommended surgical resection including nodal sampling. Note: Surgery must be lobectomy, bilobectomy, pneumonectomy, sleeve lobectomy, sleeve pneumonectomy, or chest wall resection w any of the previously listed resections. Please note that wedge resection or segmentectomy ALONE is NOTpermitted.
  • Confirmation that either EGFR-directed or ALK-directed therapy is not indicated as primary therapy (historic data with respect to the index NSCLC under study of absence of tumor-activating EGFR mutations [ie, DEL19 or L858R] or ALK mutations, or as determined by either a local or the central laboratory). Note: If participant’s tumor has a predominantly squamous histology, molecular testing for EGFR or ALK mutation is not required.
  • Has NED before randomization. Disease-free status must be confirmed based on baseline radiological assessment as documented by contrast-enhanced chest/abdomen/pelvic CT (or MRI), contrast-enhanced brain MRI (or CT), and, if part of study site SOC, whole body PET scan within 28 days prior to randomization.
  • Has received at least one dose of adjuvant treatment with standard of care platinum doublet chemotherapy up to 4 cycles (or equivalent dose of platinum doublet chemotherapy).
  • No more than 24 weeks have elapsed between surgical resection of curative intent and the first dose of pembrolizumab. Treatment should start only after adequate wound healing from the surgical procedure as assessed by the investigator. If there is a delay due to unforeseen circumstances and >24 weeks have elapsed after surgery, the eligibility should be discussed with the Sponsor and the decision documented. Participants must have recovered from surgery and any postoperative complications before the first dose of pembrolizumab. Note: Surgical resection of curative intent is defined in this protocol as the surgical procedure required to achieve complete resection of NSCLC and render the participant disease free (Appendix 9).
  • Has an FFPE tumor sample available (from their recent surgery) that is suitable for PD-L1 testing and the NGS required for this study. The tumor sample must meet the following criteria for NGS: Meet the minimum standards for tissue quantity and quality as defined in the Procedures/Laboratory manual for this study. Pass the required QC checks and successfully completed NGS by the Sponsors NGS vendor.
  • Has an ECOG PS of 0 or 1 within 7 days before the first dose of pembrolizumab.
  • Is an individual of any sex/gender, from 18 years of age inclusive, at the time of providing the full informed consent.
  • There are no contraceptive requirements for participants assigned male sex at birth.
  • The participant (or legally acceptable representative) has provided documented informed consent (full consent) for the study.
  • 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 or participants who have ≤Grade 2 neuropathy are eligible.
  • Adequate organ function as defined in the following table (Table 3). Specimens must be collected within 7 days before the start of study intervention.
  • 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 prior to randomization.
  • Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.
  • HIV-infected participants must have well controlled HIV on ART.
  • Other criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Diagnosis of SCLC or, for mixed tumors, presence of small cell elements, or has a neuroendocrine tumor with large-cell components or a sarcomatoid carcinoma.
  • HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease.
  • Received prior neoadjuvant therapy for their current NSCLC diagnosis.
  • Received or is a candidate to receive radiotherapy for their current NSCLC diagnosis.
  • Received prior treatment with another INT.
  • Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
  • Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
  • Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. Refer to Section 6.5 for information on COVID-19 vaccines.
  • Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
  • 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 the first dose of study medication.
  • Known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Participants with low-risk early stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA > Severe hypersensitivity (≥Grade 3) to either V940 or pembrolizumab and/or any of its excipients.
  • Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.
  • History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Active infection requiring systemic therapy.
  • Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Note: Hepatitis B and C screening tests are not required unless: - Known history of HBV and HCV infection - As mandated by local health authority
  • History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
  • History of allogeneic tissue/solid organ transplant.
  • Participants who have not adequately recovered from major surgery or have ongoing surgical complications.
  • Other criteria may apply.

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