Open‑Label Rollover Study of Opnurasib (JDQ443) Monotherapy or Combination Therapy in Patients with KRAS G12C‑Mutated Advanced NSCLC or Solid Tumors

The primary objective is to maintain patient access to opnurasib administered as monotherapy or in combination for individuals who have demonstrated continued clinical benefit in prior protocols, thereby supporting ongoing therapeutic management of KRAS G12C‑mutated non‑small cell lung cancer and other advanced solid tumours.

Secondary objectives focus on the evaluation of safety and tolerability of opnurasib when used alone or with other study treatments:

• Systematic collection of safety data, including adverse event incidence, severity, and relationship to opnurasib.

Sixteen patients with locally advanced or metastatic KRAS G12C‑mutated non‑small cell lung cancer or other advanced solid tumours harbouring the KRAS G12C mutation were enrolled. The cohort included both male and female adults across the protocol‑specified age categories and incorporated vulnerable participants. All individuals were selected from ongoing Novartis‑sponsored studies in which they were receiving opnurasib as monotherapy or in combination and had completed at least six treatment cycles. Eligibility required documented clinical benefit from the parent protocol, demonstrated compliance with study requirements, and provision of signed informed consent. Participants were required to be able to attend scheduled visits and adhere to the treatment plan.

The study is an open‑label, multi‑center rollover trial designed to provide continued access to opnurasib for participants with locally advanced or metastatic KRAS G12C‑mutated non‑small cell lung cancer or other advanced solid tumors harboring the KRAS G12C mutation who have completed at least six cycles of opnurasib in a preceding Novartis‑sponsored protocol and are still deriving clinical benefit. The trial does not incorporate randomization, blinding, or a control arm; all enrolled subjects receive opnurasib as monotherapy or in combination with other investigational agents per the parent study regimen. Recruitment is planned to begin on 1 June 2026 and continue until 30 September 2029, with each participant remaining in the study for the duration of continued benefit, up to the end‑of‑study visit. The visit schedule includes an initial screening visit to confirm eligibility and obtain informed consent, a baseline visit to document pre‑treatment status, regular follow‑up visits (typically every 6 weeks) to assess exposure duration, safety, tolerability, and disease status, and a final end‑of‑study visit when treatment is discontinued. Primary data collection focuses on the number of participants receiving opnurasib and the length of exposure, while secondary assessments capture the frequency and severity of adverse events and any dose modifications. Early termination may occur if the investigator determines loss of clinical benefit, unacceptable toxicity, significant protocol non‑compliance, or if the participant withdraws consent.

Batoprotafib is administered as the investigational product TNO155 in a hard capsule formulation. The capsule is taken orally; the specific dose and dosing interval are defined in the study protocol and may be adjusted based on tolerability and pharmacokinetic assessments. Administration follows a scheduled regimen, and participant adherence is monitored through returned capsule counts and electronic dosing diaries.

Cetuximab is supplied as Erbitux 5 mg/mL solution for infusion. The solution is administered intravenously according to the protocol‑specified infusion rate and schedule. Dosage amounts and frequency are determined by body surface area or weight as outlined in the protocol. Compliance is verified by infusion records and laboratory monitoring of drug levels.

Opnurasib (active ingredient of JDQ443) is provided as a tablet for oral administration. The tablet dose and dosing frequency are prescribed by the study protocol and may be modified based on clinical response. Oral intake is recorded in patient logs, and adherence is assessed by pill count at each study visit.

Tislelizumab is delivered as VDT482, a concentrate for solution for infusion. The preparation is administered intravenously following the protocol‑specified infusion schedule and duration. Dosing is guided by protocol criteria, and infusion administration is documented in the clinical record to ensure compliance.

No placebo or standard‑of‑care comparator is included in this open‑label rollover study; all participants receive the investigational agents described above as monotherapy or in combination, in accordance with the continuation criteria established in the parent protocols.