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OncoMatch/Clinical Trials/NCT07012031

Sotorasib in Combination With Trastuzumab Deruxtecan for the Treatment of Locally Advanced and Metastatic Non-small Cell Lung Cancer With a KRAS G12C Mutation

Is NCT07012031 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies multiple treatments including Trastuzumab Deruxtecan and Sotorasib for locally advanced lung non-small cell carcinoma.

Phase 1/2RecruitingNational Cancer Institute (NCI)NCT07012031Data as of May 2026

Treatment: Sotorasib · Trastuzumab DeruxtecanThis phase I/II trial tests the safety, side effects and best dose of sotorasib with trastuzumab deruxtecan and how well the combination works in treating patients with KRAS G12C mutated non-small cell lung cancer that has spread to nearby tissues or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Sotorasib blocks a protein made by the mutated KRAS gene (KRAS p.G12C), which may help keep tumor cells from growing and may kill them. It is a type of targeted therapy. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Giving sotorasib in combination with trastuzumab deruxtecan may be safe, tolerable, and/or effective in treating patients with locally advanced or metastatic non-small cell lung cancer with a KRAS G12C mutation.

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Extracted eligibility criteria

Cancer type

Non-Small Cell Lung Carcinoma

Biomarker criteria

Required: KRAS G12C mutation

KRAS^G12C-mutant NSCLC

Required: HER2 (ERBB2) mutation

Patients must also have ERBB2 (HER2) mutations status identified by tumor tissue or plasma ctDNA profiling; local (i.e., commercial or institutional next generation sequencing [NGS]) molecular testing will be allowed.

Disease stage

Required: Stage III, IV

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Prior therapy

Min 3 prior lines

Must have received: KRAS inhibitor

previously been treated with a KRAS^G12C inhibitor

Must have received: immune checkpoint inhibitor

previously been treated with ... an immune checkpoint inhibitor (ICI)

Must have received: chemotherapy

previously been treated with ... chemotherapy

Cannot have received: antibody-drug conjugate with a topoisomerase 1 inhibitor payload (sacituzumab govitecan, datopotomab deruxtecan, trastuzumab deruxtecan)

prior treatment with an antibody drug conjugate with a topoisomerase 1 inhibitor payload (i.e., sacituzumab govitecan, datopotomab deruxtecan, or trastuzumab deruxtecan) or with a topoisomerase inhibitor

Cannot have received: topoisomerase inhibitor

prior treatment with ... a topoisomerase inhibitor

Lab requirements

Blood counts

Hemoglobin ≥ 9 g/dL; leukocytes ≥ 3,000/mcL; ANC ≥ 1,500/mcL; platelets ≥ 100,000/mcL; no G-CSF within 1 week prior to screening; no transfusions with red blood cells or platelets within 1 week prior to screening

Kidney function

Creatinine ≤ 1.5 x institutional ULN OR creatinine clearance (CrCL) ≥ 30 mL/min

Liver function

Total bilirubin ≤ 1.5 x institutional ULN (or < 3 x ULN in presence of Gilbert's syndrome or liver metastases); AST/ALT ≤ 3 x ULN (or < 5 x ULN with liver metastases)

Cardiac function

LVEF ≥ 50% by ECHO or MUGA within 28 days before enrollment; QTc ≤ 470 msec for women and ≤ 450 msec for men

Hemoglobin ≥ 9 g/dL ... Platelets ≥ 100,000/mcL ... Total bilirubin ≤ 1.5 x institutional ULN ... AST/ALT ≤ 3 x institutional ULN ... Creatinine ≤ 1.5 x institutional ULN OR CrCL ≥ 30 mL/min ... LVEF ≥ 50% ... QTc ≤ 470 msec for women and ≤ 450 msec for men

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • Moffitt Cancer Center-International Plaza · Tampa, Florida
  • Moffitt Cancer Center - McKinley Campus · Tampa, Florida
  • Moffitt Cancer Center · Tampa, Florida
  • Moffitt Cancer Center at Wesley Chapel · Wesley Chapel, Florida

Showing up to 5 US sites. See all sites on ClinicalTrials.gov →

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