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

• Status: Recruiting
• Trial end date: 2026-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this interventional study is to learn about the combination of sotorasib and stereotactic radiation therapy (SBRT) in patients with metastatic non-small cell lung cancer (NSCLC) with KRASG12C mutations. The main question it aims to answer is:

• can SBRT be safely delivered in patients treated with sotorasib

Participants will be treated with sotorasib for an 8-week-induction period and if the patient has stable disease or partial response, 1-3 of the remaining lesions will be irradiated with SBRT and sotorasib will then be contiuned after irradiation. The patients will then be followed and evaluated for toxicity to identify if grade 3-5 toxicity attributed to SBRT occurs within 6 months post SBRT. Tumour effects measured according to RECIST v1.1 will also be evaluated.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Karolinska University Hospital
• Collaborators: Amgen; Sahlgrenska University Hospital, Sweden
• Treatments: Sotorasib

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.