Combination of sotorasib and radiation therapy for advanced lung cancer with KRASG12C mutation

K-SAB Trial - Sotorasib Followed by SBRT to 1-3 Lesions in Advanced NSCLC With KRASG12C Mutation

This study is testing if combining a new lung cancer drug called sotorasib with targeted radiation therapy can help people with advanced lung cancer that has a specific genetic mutation feel better and respond to treatment.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Karolinska University Hospital (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Stockholm, Solna)
• Trial ID: NCT06127940 on ClinicalTrials.gov

What this trial studies

This interventional study aims to evaluate the safety and efficacy of combining sotorasib with stereotactic body radiation therapy (SBRT) in patients with advanced non-small cell lung cancer (NSCLC) harboring KRASG12C mutations. Participants will undergo an 8-week induction treatment with sotorasib, followed by SBRT targeting 1-3 lesions if they show stable disease or partial response. The study will monitor patients for toxicity and tumor response according to RECIST criteria, with follow-up evaluations conducted monthly for the first six months post-SBRT. A safety review will occur after the first 10 patients are treated to determine the feasibility of including additional participants.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced NSCLC confirmed to have KRASG12C mutations and who have previously received at least one line of standard treatment.

Not a fit: Patients with leptomeningeal carcinomatosis, central nervous system metastases, or those who have had prior radiation therapy for any cancer within the last three years may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option that enhances the effectiveness of sotorasib in managing advanced NSCLC with KRASG12C mutations.

How similar studies have performed: While the combination of targeted therapies and radiation is a growing area of interest, this specific approach involving sotorasib and SBRT in KRASG12C mutated NSCLC is novel and has not been extensively tested in prior studies.

Eligibility criteria

Main inclusion criteria:

1. Histological or cytological confirmed advanced NSCLC
2. KRASG12C mutation
3. Previous at least one line of treatment with immune- or/and chemotherapy or contraindications for immune- and/or chemotherapy.
4. Adequate organ function to tolerate sotorasib (see section 6.1 and 6.2 for details)
5. 2-5 lesions technically amenable to SBRT with 15 Gy x 3, 10 Gy x 5, or 7-8 Gy x 5.
6. Adequate organ function to tolerate SBRT:

   o Fulfilment of dose constraints to adequate organs at risk
7. ECOG performance status (PS) 0-1
8. FEV1 ≥1 litre (only applicable for lung targets)
9. Age ≥ 18 years
10. Measurable lesions according to RECIST

Main exclusion criteria:

1. Leptomeningeal carcinosis (on MRI or in cerebrospinal fluid) or metastases in the central nervous system
2. Previous RT for any cancer within the last 3 years possibly interfering with the planned RT within this study
3. Life expectancy of less than 6 months
4. Inability to understand given information or undergo study procedures according to protocol
5. Has evidence or a past medical history of interstitial lung disease or active, non-infectious pneumonitis or known pulmonary fibrosis
6. Woman who is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 7 days after the last dose of sotorasib
7. Women of childbearing potential (WOCBP) unwilling to use a highly effective method of contraception during treatment and for an additional 7 days after the last dose of sotorasib. WOCBP using hormonal contraceptives should also use a barrier method
8. WOCBP with a positive pregnancy test assessed at screening or day 1 by a serum pregnancy test and/or urine pregnancy test
9. Centrally located pulmonary target (i.e., within 1 cm of the main bronchi or intermedius bronchus) and targets located within 1 cm of the gut, for SBRT
10. Use of known cytochrome P450 (CYP) 3A4 or P-gp sensitive substrates (with a narrow therapeutic window), within 14 days or 5 half-lives of the drug or its major active metabolite, whichever is longer, prior to study day 1 that was not reviewed and approved by the principal investigator
11. Use of strong inducers of CYP3A4 (including herbal supplements such as St. John´s wort) within 14 days or 5 half-lives, whichever is longer, prior to study day 1 that was not reviewed and approved by the principal investigator
12. Use of proton pump inhibitors (PPIs) within 3 days or H2-receptor antagonists within 1 day prior to study intervention
13. Use of warfarin. Use of Direct-Acting Oral Anticoagulants (DOAC) within 14 days or 5 half-lives, whichever is longer, prior to study day 1. Other anticoagulation may be allowed with principal investigator approval.

Where this trial is running

Stockholm, Solna

• Karolinska University Hospital — Stockholm, Solna, Sweden (Recruiting)

Study contacts

• Principal investigator: Karin Lindberg, MD, PhD — Karolinska University Hospital
• Study coordinator: Karin Lindberg, MD, PhD

Conditions Non-small Cell Lung Cancer Metastatic; Stereotactic body radiation therapy; KRAS-G12C mutation; NSCLC