What is CMN-001?
This approach offers the following advantages:
- CMN-001 is specifically engineered to function in the immune suppressed environment of cancer patients
- Captures all tumor antigens including “private” mutated antigens from the patient’s own tumor without the need to identify them
- Engineered to induce tumor-specific memory T cell responses that are reported to correlate with survival
*Mol Ther Nucleic Acids (2013) 7:2
CMN-001-1 Phase 2b trial design
CMN-001-1 Phase 2b Trial Quick Facts
- The only difference between the trial arms is CMN-001 administration in the Combo arm
- Trial population: Poor risk (≥3 risk factors) with up to 50% 2-risk factor intermediate patients
- Patients that leaver the trial for any reason prior to starting 2nd line will be replaced
- CT scans showing progression will be confirmed with a second scan no less than four weeks later (iRECIST)
- CMN-001 dosing
- Induction: 3 doses 3 weeks apart
- Maintenance: 7 doses 4 weeks apart
- Booster: Every 12 weeks until second confirmed progression
- Primary endpoint: OS
- Open and accruing
- Expect to collect ~135 tumors, enroll ~110 to get 90 patients
- Total of 10 clinical sites planned
Rationale for the trial design
CMN-001 has been shown to be clinically effective and safe in a previous randomized, controlled trial. That trial treated 462 patients with metastatic renal cell carcinoma; 155 patients treated with standard of care therapies and 307 treated with standard of care therapy plus CMN-001. Based on these clinical data, CMN-001-1 was optimized to maximize the clinical benefit.
Why treat patients with the most advanced disease?
Data on all 462 patients showed that there was a linear relationship between the number of Heng risk factors (a measure of the severity of disease) and clinical benefit. The more risk factors present, the lower the hazard ratio (comparison between the study arms). The lower the hazard ratio the greater the survival difference between the study arms. CMN-001-1 will therefore enroll primarily poor risk patients.
The importance of everolimus in second line treatment
CMN-001 was shown to strongly synergize with mTOR inhibitors such as everolimius which is FDA approved for the treatment of advanced renal cell carcinoma. In fact, 91 of 462 patients received everolimus either in combination with CMN-001 or after administration of CMN-001. Patients that received everolimus + CMN-001, especially those that received everolimus after CMN-001 had a significant survival advantage over patients receiving everolimus alone.
CMN-001-1 is designed to provide everolimus in second line, after CMN-001 administration is initiated to take maximum advantage of the observed synergy.