Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

All Drugs and Chemicals

Antineoplastic Agents

Tin Fluorides

Sotorasib

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Sotorasib is administered as an 8-week-introduction treatment and if response on a CT-scan is observed (stable disease or partial response), the patient is treated with stereotactic radiation therapy (SBRT) to 1-3 of the remaining lesions.

SBRT is delivered using institutional standard dosing while sotorasib is withheld during radiation.

Stereotactic body radiation therapy (SBRT)

Temporary Stopping

Karin Lindberg, MD, PhD

Reka Conrad, PhD

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.

Eligible subjects are those with a diagnosis of advanced KRASG12C mutated NSCLC who have received at least one line of standard medical treatment with immuno(chemo)therapy.

The subjects start with sotorasib and in parallel, 2-5 target lesions which are technically feasible to treat with SBRT, are identified. After 8 weeks of induction treatment of with sotorasib, the subjects are radiologically evaluated and subjects with stable disease (SD) or partial response (PR) on sotorasib will receive SBRT to minimum 1 and maximum 3 of the predefined lesions. Sotorasib is withheld during SBRT and then restarted after SBRT.

Sotorasib will continue until progression or other discontinuation criteria are met. The patients are followed clinically every month during the first 6 months post SBRT and then every 2-3 months. Radiological evaluation is performed every 2 months during the first year.

After the first 10 treated patients, a safety review meeting will be held and a decision whether to include 10 more patients will be performed.

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

Prevalence of intrinsic and induced resistance mechanisms in response to KRASG12C inhibition with sotorasib.

The number of patients presenting with grade 3-5 toxicity (attributed to SBRT) within 6 months post SBRT.

The number of patients who have progressed or died during the first 12 months post start of sotorasib (estimated using the KM-method).

The time between the date of first observation of CR or PR and the date of documented progressive disease for evaluable subjects. In all other situations, observations will be censored, or analysis only performed on those subjects who achieve a response.

The number of patients who have died during the first 12 months post start of sotorasib (estimated using the KM-method).

No and percentage of patients suffering toxicity attributed to SBRT (early toxic effects presenting within 3 months of finalization of SBRT vs late toxic effects presenting after more than 3 months post completion of SBRT).

No and percentage of patients suffering toxicity attributed to sotorasib (early toxic effects presenting within 3 months of finalization of SBRT vs late toxic effects presenting after more than 3 months post completion of SBRT).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
K-SAB Trial - Sotorasib Followed by SBRT to 1-3 Lesions in Advanced NSCLC With KRASG12C Mutation	NCT06127940	Non-small Cell ...	Stereotactic bo... Temporary Stopp...	18 Years -	Karolinska University Hospital
K-SAB Trial - Sotorasib Followed by SBRT to 1-3 Lesions in Advanced NSCLC With KRASG12C Mutation	NCT06127940	Non-small Cell ...	Stereotactic bo... Temporary Stopp...	18 Years -	Karolinska University Hospital

Spots Global Cancer Trial Database for temporary stopping