Adjuvant calderasib with subcutaneous pembrolizumab plus berahyaluronidase alfa for completely resected KRAS G12C stage IIA–IIIB (N2) NSCLC

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a randomized, double‑blind phase 3 trial comparing adjuvant calderasib plus MK-3475A (subcutaneous pembrolizumab and berahyaluronidase alfa) versus placebo plus MK-3475A in participants with completely resected stage IIA–IIIB (N2) KRAS G12C NSCLC. Eligible participants must have no radiographic evidence of disease after surgery and received either neoadjuvant pembrolizumab plus chemotherapy or adjuvant platinum‑doublet chemotherapy, with the first adjuvant dose given within 12 weeks of surgery or last chemotherapy. The primary endpoint is investigator‑assessed disease‑free survival; participants are randomized and treated in a double‑blind fashion to isolate the effect of calderasib. Safety and secondary clinical endpoints will also be collected to compare outcomes between the two arms.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Has a histological/cytological diagnosis of non-small cell lung cancer (NSCLC) with predominantly nonsquamous histology and meets one of the following criteria:

  * Has newly diagnosed, treatment-naïve, resectable, clinical Stage IIA-IIIB (N2) NSCLC
  * Has completely resected, pathological Stage IIA-IIIB (N2) NSCLC, including those previously treated outside the study with neoadjuvant platinum-doublet chemotherapy plus pembrolizumab or MK-3475A, or those who received adjuvant platinum-doublet chemotherapy.
* Tumor tissue shows the presence of Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation
* No more than 12 weeks have elapsed between either the surgery following neoadjuvant treatment or last dose of adjuvant platinum-based chemotherapy and the first dose of investigational adjuvant study intervention.
* Has no evidence of disease based on postsurgical radiological assessment as documented by contrast-enhanced chest/abdomen computed tomography (or magnetic resonance imaging) within 28 days before randomization
* Has an Eastern Cooperative Oncology Group performance status of 0 or 1 within 10 days before the first dose of the study intervention
* Human immunodeficiency virus-infected participants must have well controlled HIV on antiretroviral therapy
* Participants who are Hepatitis B surface antigen positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable

Exclusion Criteria:

* Has a diagnosis of any 1 of the following tumor types/locations: small cell lung cancer or, for mixed tumors, presence of small cell elements, neuroendocrine tumor with large cell components, sarcomatoid carcinoma, or NSCLC involving the superior sulcus
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within the 6 months preceding study intervention
* Is unable to swallow orally administered medication, or has a gastrointestinal disorder affecting absorption (e.g. gastrectomy, partial bowel obstruction, or malabsorption)
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has an active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has active infection requiring systemic therapy
* Has not adequately recovered from major surgery or has ongoing surgical complications

Where it's running

• Instituto Alexander Fleming ( Site 0310)
  Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina Recruiting
• Sanatorio Parque ( Site 0311)
  Rosario, Santa Fe Province, Argentina Recruiting
• Hospital Italiano de Buenos Aires-Clinical Oncology ( Site 0306)
  Caba, Argentina Recruiting
• Centro de Educación Médica e Investigaciones clínicas "Dr. Norberto Quirno" (CEMIC) ( Site 0309)
  Caba, Argentina Recruiting
• Northern Beaches Hospital ( Site 3009)
  Frenchs Forest, New South Wales, Australia Recruiting
• Princess Alexandra Hospital ( Site 3012)
  Woolloongabba, Queensland, Australia Recruiting

+72 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Toll Free Number
• Email: Trialsites@msd.com
• Phone: 1-888-577-8839

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.