Sotorasib in patients with non-small cell lung cancer with genetic changes with comorbidities

Phase 1

• Conditions: Advanced KRASG12C-mutated non-small cell lung cancer patients with comorbidities; MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 25.1Level: LLTClassification code 10069759Term: KRAS mutationSystem Organ Class: 100000004850; MedDRA version: 20.0Level: LLTClassification code 10025044Term: Lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 22.0Level: LLTClassification code 10075674Term: KRAS codon 12 and 13 mutationSystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-001696-16-NO
• Lead Sponsor: Vestre Viken Health Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-26
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

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.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.
3.Major surgery within 4 weeks of inclusion
4.RT within 2 weeks of inclusion
5.Previous treatment with sotorasib or other KRASG12C inhibitor
6.Use of warfarin. Other anticoagulation is allowed.
7.Patients with significant comorbidities other than those mentioned below:
?Comorbidities of special interest(up to grade 2 according to ACE-27 scoring system), 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:
-Autoimmune diseases (rheumatoid, colitis, diabetes, skin,multiple sclerosis etc), including immunotherapy-induced morbidity (colitis, pneumonitis,endocrinopathies, hepatitis, nephritis etc). Immunotherapy-induced colitis or pneumonitis must be resolved to max CTCAE 2, and a max use of prednisolone 10 mg or equivalent is allowed.
-Smoking-induced diseases (cardiovascular (coronary artery disease, apoplexia, thromboembolic events), COPD/emphysema etc)
8.Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator’s opinion makes it undesirable to participate in the trial or could jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and HIV. Screening for chronic conditions is not required.
9.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 PI.
10.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.
11.Significant gastrointestinal disorder that results in significant malabsorption, requirement for intravenous alimentation, or inability to take oral medication.
12.Mean resting corrected QT interval (QTc) > 470 msec (females) or > 450 msec (males) using the screening clinic ECG machine derived QTc value.
13.Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
-Absolute neutrophil count <1.5x109/L
-Platelet count <100x109/L
-Haemoglobin <9.0g/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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified