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

NCT ID: NCT06127940

Last Updated: 2023-11-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-15
• Study Completion Date: 2026-01-01

Brief 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.

Detailed 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.

Conditions

Non-small Cell Lung Cancer Metastatic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiotherapy + sotorasib

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.

Group Type: EXPERIMENTAL

Stereotactic body radiation therapy (SBRT)

Intervention Type: RADIATION

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

Temporary Stopping

Intervention Type: DRUG

Temporary stop of sotorasib during SBRT

Interventions

Stereotactic body radiation therapy (SBRT)

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

Intervention Type: RADIATION

Temporary Stopping

Temporary stop of sotorasib during SBRT

Intervention Type: DRUG

Other Intervention Names

Sotorasib

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sahlgrenska University Hospital

OTHER

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: collaborator

Karolinska University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Karin Lindberg

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Karin Lindberg, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska University Hospital

Locations

Karolinska University Hospital

Stockholm, Solna, Sweden

Site Status: RECRUITING

Countries

Sweden

Central Contacts

Karin Lindberg, MD, PhD

Role: CONTACT

karin.lindberg@ki.se

+46851770000

Reka Conrad, PhD

Role: CONTACT

reka.conrad@regionstockholm.se

+46851770000

Facility Contacts

Karin Lindberg, MD, PhD

Role: primary

Other Identifiers

K-SAB

Identifier Type: -

Identifier Source: org_study_id