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

Non-small Cell Lung Cancer Metastatic Clinical Trial

— K-SAB  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06127940
• Other study ID #: K-SAB
• Status: Recruiting
• Phase: Phase 1
• Start date: October 15, 2023
• Est. completion date: January 1, 2026

Study information

• Verified date: November 2023
• Source: Karolinska University Hospital
• Contact: Karin Lindberg, MD, PhD
• Phone: +46851770000
• Email: karin.lindberg[@]ki.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: January 1, 2026
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-small Cell Lung Cancer Metastatic

Intervention

Radiation:
• Stereotactic body radiation therapy (SBRT)
SBRT is delivered using institutional standard dosing while sotorasib is withheld during radiation.

Drug:
• Temporary Stopping
Temporary stop of sotorasib during SBRT

Locations

Country	Name	City	State
Sweden	Karolinska University Hospital	Stockholm	Solna

Sponsors (3)

Lead Sponsor	Collaborator
Karolinska University Hospital	Amgen, Sahlgrenska University Hospital, Sweden

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory outcome	Prevalence of intrinsic and induced resistance mechanisms in response to KRASG12C inhibition with sotorasib.	1 year
Primary	Safety - Grade 3 - 5 toxicity attributed to SBRT	The number of patients presenting with grade 3-5 toxicity (attributed to SBRT) within 6 months post SBRT.	6 months post SBRT
Secondary	Progression free survival	The number of patients who have progressed or died during the first 12 months post start of sotorasib (estimated using the KM-method).	1 year
Secondary	Duration of response	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.	1 year
Secondary	Overall survival	The number of patients who have died during the first 12 months post start of sotorasib (estimated using the KM-method).	1 year
Secondary	Overall toxicity related to SBRT	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).	1 year
Secondary	Overall toxicity related to sotorasib	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).	1 year