Sotorasib in Advanced KRASG12C-mutated Non-small Cell Lung Cancer Patients With Comorbidities

NCT05311709 | Unknown Phase 2

• 1 other identifier: SOLUCOM
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

A single-arm, multicentre trial to investigate sotorasib in KRASG12C-mutated non-small cell lung cancer stage III/IV not amenable for curative treatment including patients with comorbidities, and to provide translational knowledge regarding mechanism of relapse and differences in responses, including differences among patients with different co-occurring mutations.

Conditions

Lung Cancer; NSCLC, Stage III; NSCLC Stage IV; Lung Cancer Stage IV; Mutation; Cancer; Cancer, Lung

Keywords

KRAS G12C

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) of sotorasib reducing tumour size in the all subjects treated

  Evalution of tumour size by RECIST v1.1 criteriae

  every eigth week until progression, or up to 2 years

Secondary Outcomes (13)

• Objective Response Rate (ORR) of sotorasib reducing tumour size in the predefined patient groups (including ECOG PS2, specific comorbidities, including immune-related adverse events after (chemo-)immunotherapy)

  from study baseline and every eigth week until progression, or or up to 2 years

• Evaluation of efficacy of sotorasib in pre-defined patient groups

  From study baseline, through study completion, and average of 8 months

• Evaluation of efficacy of sotorasib (response) in pre-defined patient groups

  from baseline, through study completion, and average of 8 months

• Evaluation of efficacy and disease control of investigational medicinal product sotorasib in pre-defined patient groups

  from baseline, through study completion, and average of 8 months

• Evaluation of efficacy of sotorasib in pre-defined patient groups

  from baseline, through study completion, and average of 8 months

Other Outcomes (9)

• To investigate molecular factors involved in response, resistance and toxicity

  through study completion, and average of 8 months

• To investigate factors involved in response, resistance and toxicity by deep sequencing of tumor tissue

  through study completion, and average of 8 months

• To investigate factors involved in response, resistance and toxicity by molecular analyses of blood

  through study completion, and average of 8 months

Study Arms (1)

Sotorasib

EXPERIMENTAL

Single arm trial. All patients will be included in this interventional arm.

Drug: sotorasib

Interventions

sotorasib DRUG

single group, all patients receive sotorasib

Sotorasib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated, written informed consent.
• Age \> 18 years.
• 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.
• Adjuvant therapy will count as a line of therapy if the subject progressed on or within 6 months of adjuvant therapy administration.
• Disease progression on or within 6 months of end of prior curatively intended multimodal therapy will count as a line of therapy.
• 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.
• 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.
• Male subjects must be willing to use barrier contraception.
• Mean resting corrected QT interval (QTc) \< 470 msec (females) or \< 450 msec (males) using the screening clinic ECG machine derived QTc value.
• 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

You may not qualify if:

• 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).
• Symptomatic brain metastases or leptomeningeal disease. Subjects that have received whole brain radiation therapy ending at least 4 weeks (or stereotactic radiosurgery ending at least 2 weeks) prior to study day 1 are eligible if they meet all the following criteria: a) residual neurological symptoms grade ≤ 2; b) on stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable; and c) follow-up MRI performed within 30 days prior to enrolment shows no progression or new lesions appearing.
• 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.
• Previous treatment with sotorasib or other KRASG12C inhibitor
• Use of warfarin. Other anticoagulation is allowed.
• 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 etc). 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.
• 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.
• History of hypersensitivity of active or inactive excipients of sotorasib or drugs with a similar chemical structure or class to sotorasib.
• Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater.

Sponsors & Collaborators

• Vestre Viken Hospital Trust: lead
• Aarhus University Hospital: collaborator
• Oslo University Hospital: collaborator
• Rigshospitalet, Denmark: collaborator
• Odense University Hospital: collaborator
• Karolinska University Hospital: collaborator
• University Hospital of North Norway: collaborator
• Haukeland University Hospital: collaborator
• St. Olavs Hospital: collaborator

Study Sites (1)

Vestre Viken Health Trust

Drammen, Akershus, 3004, Norway

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

sotorasib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Odd Terje Brustugun, MD, PhD

  Vestre Viken Health trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Odd Terje Brustugun, MD, PhD

CONTACT

+4732862464; otr@vestreviken.no

Inger-Johanne Eide, MD, PhD

CONTACT

+4799713251; ingei@vestreviken.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm, multinational phase II trial

Study Record Dates

• First Submitted: September 20, 2021
• First Posted: April 5, 2022
• Study Start: May 30, 2022
• Primary Completion: October 1, 2024
• Study Completion: March 1, 2025
• Last Updated: November 9, 2023

Record last verified: 2023-11

Locations

NO (1)