Sotorasib in advanced KRAS G12C-mutated non-small cell lung cancer patients with comorbidities (SOLUCOM)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vestre Viken HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

30 May 2022 → ongoing

Decision date (initial)

2024-09-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Amgen AB

External identifiers

EU CT number

2023-503174-20-00

EudraCT number

2021-001696-16

ClinicalTrials.gov

NCT05311709

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Others, Safety

To evaluate the efficacy of sotorasib in reducing tumour size in the all subjects treated population

Secondary objectives 5

1. To evaluate the efficacy of sotorasib in reducing tumour size in the predefined patient groups (including ECOG PS2, specific comorbidities, including immune-related adverse events after (chemo-)immunotherapy)
2. To further assess efficacy parameters in both the all subjects treated populations as in the predefined patient groups
3. To evaluate patient-reported outcome during treatment assessed by the following questionnaires: European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 13 (EORTC QLQ-LC13), European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and EuroQol 5-dimensional descriptive system (EQ-5D-5L)
4. To assess the safety profile of sotorasib
5. To investigate factors involved in response, resistance and toxicity

Conditions and MedDRA coding

KRAS G12C-mutated non-small cell lung cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Provision of signed and dated, written informed consent.
2. Age > 18 years.
3. Histologically or cytologically documented NSCLC stage III/IV not amenable for curative treatment. Patients that have received systemic adjuvant therapy for non-metastatic disease in the past will need a new biopsy before inclusion if no biopsy acquired after adjuvant therapy is available.
4. Documented KRASG12C mutation, based on tissue analysis on either archived tissue or new biopsy before inclusion, and verified locally by a validated method.
5. Subjects will have received and progressed or experienced disease recurrence on or after receiving at least 1 prior systemic therapy for NSCLC stage III/IV not amenable for curative treatment. Prior treatment must include checkpoint inhibitor for advanced or metastatic disease, either given alone or in combination with chemotherapy unless the subject has a medical contraindication to one of the required therapies. a. Adjuvant therapy will count as a line of therapy if the subject progressed on or within 6 months of adjuvant therapy administration. b. Disease progression on or within 6 months of end of prior curatively intended multimodal therapy will count as a line of therapy.
6. ECOG status 0-2 and a minimum life expectancy of 12 weeks. At least 60 patients should be in ECOG 2. When 40 patients in ECOG 0-1 are included, the inclusion criteria will change to only ECOG 2.
7. At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline according to RECIST 1.1. Brain metastases are not regarded measurable.
8. Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:  Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments  Women under 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels in the post-menopausal range for the institution  Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
9. Male subjects must be willing to use barrier contraception.
10. Mean resting corrected QT interval (QTc) < 470 msec (females) or < 450 msec (males) using the screening clinic ECG machine derived QTc value.
11. Adequate bone marrow reserve or organ function (as demonstrated by any of the following laboratory values:  Absolute neutrophil count > 1.5 x 109/L  Platelet count > 100 x 109/L  Haemoglobin > 9.0 g/dL  Alanine aminotransferase (ALT) < 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or < 5 times ULN in the presence of liver metastases  Aspartate aminotransferase (AST) < 2.5 times ULN if no demonstrable liver metastases or < 5 times ULN in the presence of liver metastases  Total bilirubin < 1.5 times ULN if no liver metastases or < 3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases  Serum creatinine < 1.5 times ULN concurrent with creatinine clearance > 45 mL /min [measured or calculated by Cockcroft and Gault equation]-confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN

Exclusion criteria 15

1. Previously identified driver mutation (according to local standard of care or guidelines) other than KRASG12C for which an approved therapy is available (including EGFR, ALK, etc).
2. History of hypersensitivity of active or inactive excipients of sotorasib or drugs with a similar chemical structure or class to sotorasib.
3. Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater.
4. Any unresolved toxicities from prior therapy greater than CTCAE grade 2, unless discussed with Sponsor.
5. Women who are pregnant or breast-feeding, or have a positive (urine or serum) pregnancy test prior to study entry
6. Involvement in the planning and/or conduct of the study (investigator staff and/or staff at the study site).
7. Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.
8. Subjects with symptomatic CNS metastases or leptomeningeal disease who are neurologically unstable or have required increasing doses of steroids to manage CNS symptoms within the 2 weeks prior to study day 1.
9. Major surgery within 4 weeks of inclusion
10. Radiotherapy treatment within 2 weeks of inclusion. Subjects must have recovered from all radiotherapy related toxicity to CTCAE version 5.0 grade 1 or less with the exception of alopecia (any grade of alopecia allowed).
11. Anti-tumour therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy [except for subjects with history of completely resected breast cancer with no active disease on long term adjuvant endocrine therapy], or investigational agent) within 4 weeks (chemotherapy within 2 weeks) of study day 1. Targeted small molecule inhibitors, within 14 days of study day 1, or within 5 half-lives, whichever is longer. Please note that bisphosphonates or anti RANKL antibody therapy is allowed if needed for management of hypercalcemia or for prevention of skeletal events.
12. Previous treatment with sotorasib or other KRASG12C inhibitor
13. Use of warfarin. Other anticoagulation is allowed.
14. Patients with significant comorbidities other than those mentioned below:  Comorbidities of special interest (up to grade 2 according to ACE-27 scoring system (see appendix A and (20)), or toxicity CTCAE 2) are eligible (ACE-27 grade 3 or CTCAE grade 3 may be eligible after discussion with Sponsor). Patients may have more than one comorbidity as long as all are within the severity grades as mentioned. Comorbidities of special interest are the following: i. Autoimmune diseases (rheumatoid, colitis, diabetes, skin, multiple sclerosis etc), including immunotherapy-induced morbidity (colitis, pneumonitis, endocrinopathies, non-viral hepatitis, nephritis etc). Immunotherapy-induced colitis or pneumonitis must be resolved to maximum CTCAE 2, and a maximum use of prednisolone 10 mg or equivalent is allowed. ii. Smoking-induced diseases (cardiovascular (coronary artery disease, apoplexia, thromboembolic events), COPD/emphysema). Note: Myocardial infarction within 6 months prior to enrolment, unstable arrhythmias or unstable angina are not eligible.  The following comorbidities are ineligibility criteria: i. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required. ii. Previous malignancy (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, oesophageal, colon, endometrial, cervical, melanoma or breast) unless a complete remission was achieved at least 2 years prior to study entry. iii. Significant gastrointestinal disorder that results in requirement for intravenous alimentation, or inability to take oral medication.
15. Use of known cytochrome P450 (CYP) 3A4 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. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective Response Rate (ORR) of sotorasib in the all subjects treated population

Secondary endpoints 21

1. Objective Response Rate (ORR) of sotorasib in the predefined patient groups (including ECOG PS2, specific comorbidities, including immune-related adverse events after (chemo-) immunotherapy)
2. Progression Free Survival (PFS)
3. Duration of Response (DoR)
4. Disease Control Rate (DCR)
5. Intracranial Disease Free Survival (iDFS)
6. Intracranial Time To Recurrence (iTTR)
7. Tumour shrinkage
8. Overall Survival (OS)
9. Time on treatment post progression
10. Change from baseline over time to week 12 in disease related symptoms, physical functioning and global health status as measured by QLQ-C30 and QLQ-LC13
11. To estimate the subject incidence of treatment-emergent adverse events, treatment-related adverse events, changes in vital signs, and clinical laboratory tests
12. Molecular characterization (see below) of blood and tissue before commencement on sotorasib, at response and at progression on sotorasib
13. NGS (deep targeted sequencing of tumour tissue), STK11/LKB1, KEAP1, p53 etc
14. Molecular analyses (incl NGS, e.g. Avenio) of blood samples (ctDNA)
15. Array-based microRNA, methylation, mRNA expression
16. Protein analyses based on IHC, including immune-markers as PD-L1, IL-10, STING, TGFbeta etc
17. Exploratory analyses to be determined
18. Intracranial Objective Response Rate (iORR)
19. Intracranial Disease Control Rate (iDCR)
20. Intracranial Duration of response (iDoR)
21. Intracranial Progression Free Survival (iPFS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vestre Viken HF

Sponsor organisation

Vestre Viken HF

Address

Groenland 32

City

Drammen

Postcode

3045

Country

Norway

Scientific contact point

Organisation

Vestre Viken HF

Contact name

Odd Terje Brustugun

Public contact point

Organisation

Vestre Viken HF

Contact name

Odd Terje Brustugun

Third parties 1

Locations

3 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 38 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications