Medidata

• The study enrolled 9 participants across France, Israel, Italy, and the Republic of Korea.
• A May 2022 amendment changed the design from a single-arm two-stage study to a single-arm study with two interim analyses.
• Eligibility criteria were updated in amendments dated May 2022 and March 2023.
• A March 2023 amendment updated definitions for time to first deterioration in cough, pain, dyspnea, and physical functioning.
• Paper diary cards were added for sites in China in a March 2023 amendment.

These findings describe the trial, not the service provider’s performance or responsibility.

• The trial had no global interruptions.
• The two independent studies used a common screening platform, and entry into the remission-withdrawal period was optional.
• COVID-19 logistical restrictions accounted for one open-label Study 1 non-completion.
• Geopolitical restrictions accounted for four open-label Study 1 and one open-label Study 2 non-completions.
• A global amendment removed the Japan substudy from Study 1 and revised the number of participating countries to approximately 25.
• MRI eligibility was clarified, and participants with MRI contraindications were excluded.

These findings describe the trial, not the service provider’s performance or responsibility.

• The Phase 2 dose-expansion phase was not initiated.
• A 12 April 2023 protocol amendment revised prior-anticancer-therapy eligibility from requiring BRAFi-naive participants to requiring prior BRAFi treatment when appropriate.
• A 6 February 2024 protocol amendment added CFT1946 plus cetuximab arms for BRAF V600-mutant colorectal cancer and updated enrollment stopping rules and eligibility criteria.

These findings describe the trial, not the service provider’s performance or responsibility.

• The study used 46 sites across Canada (10), Czechia (3), Germany (2), Hungary (3), Poland (8), Spain (3), the United Kingdom (3), and the United States (14).
• A total of 293 participants signed consent and 229 were randomized, compared with approximately 225 participants planned for randomization.
• Enrollment was geographically balanced between North America/Western Europe (53.1%) and Eastern Europe (46.9%).

These findings describe the trial, not the service provider’s performance or responsibility.

• The trial was conducted at 12 centers in Europe and the United States, of which 8 centers enrolled participants.
• Forty-two participants were screened by 9 sites, and 35 participants were enrolled over approximately 16 months.
• The planned Phase 2a part was not initiated.

These findings describe the trial, not the service provider’s performance or responsibility.

• The study assessed 2 patients and treated 1 patient before termination.
• Delayed study start-up and slow patient recruitment prevented completion of planned enrollment on time.

These findings describe the trial, not the service provider’s performance or responsibility.

• A global amendment increased the planned eligible sample from 1500 to approximately 2510 because low global COVID-19 hospitalization and death rates reduced endpoint event rates.
• Rapid enrollment prevented the planned interim analysis after 65% of subjects completed Day 29 assessments; consequently, adolescent enrollment was not recommended and no pediatric subjects were enrolled.
• Of 218 screen failures, 177 were due to failure to meet entry criteria.
• Enrollment was concentrated in North America (1811/2285 subjects), whereas Europe enrolled 57 subjects, Asia 170 subjects, and other countries 247 subjects.

These findings describe the trial, not the service provider’s performance or responsibility.

• Approximately 50% of the first 22 Part 1 participants experienced on-treatment ALT elevations, and protocol management criteria were amended because some elevations were prolonged.
• New enrollment was temporarily halted in December 2022 after significant ALT elevations were observed more frequently in Part 2 participants with screening or baseline HBsAg >10,000 IU/mL.
• Enrollment was not reopened because the sponsor discontinued further investment in its hepatitis B and D discovery and development programs.
• Part 2 open-label treatment was reduced to Week 96 and follow-up to 24 weeks under protocol amendment 5.
• Sustained HBV response was not collected or analyzed because follow-up was shortened and participants continued NA treatment during follow-up.

These findings describe the trial, not the service provider’s performance or responsibility.