A Phase 1/2 Open Label, Dose Escalation and Expansion Study of MDNA11, IL-2 Superkine, Administered Alone or in Combination With Immune Checkpoint Inhibitor in Patients With Advanced Solid Tumors
Summary
This is a Phase 1/2, multi-center, open-label, dose-escalation and expansion study to evaluate safety and tolerability, PK, pharmacodynamic, and early signal of anti-tumor activity of MDNA11 alone or in combination with a checkpoint inhibitor in patients with advanced solid tumors.
Detailed description
The study drug, MDNA11, long-acting "beta-only" recombinant interleukin-2 (rIL-2). MDNA11 specifically engineered to overcome the shortcomings of rhIL-2 (aldesleukin) by preferentially activating immune effector cells (CD8+ T- and NK cells) responsible for killing cancer cells, with minimal or no stimulation of immunosuppressive Tregs. It is designed to potentially enhance host immune response and fusion to albumin increases the half-life further avoiding frequent dosing required with rhIL-2. The study will be conducted at up to 30 clinical sites following regulatory authority and institutional review board / independent ethics committee (IRB/ IEC) approval and completion of informed consent. The study will be conducted in multiple parts: * Monotherapy (MDNA11 alone) dose escalation * Monotherapy (MDNA11 alone) dose expansion in select tumor types * Combination (MDNA11 + pembrolizumab) dose escalation * Combination (MDNA11 + pembrolizumab) dose expansion in select tumor types Approximately 115 patients will be enrolled. After commencing treatment (first exposure of MDNA11 alone or MDNA11 + pembrolizumab), tumor assessment by CT/MRI will be performed every 8 weeks ± 1 week until immune confirmed progressive disease ("iCPD") by iRECIST, discontinuation of study drug(s), withdrawal of consent or loss to follow-up. Treatment beyond progression may be permitted if criteria are met. Patients can withdraw from participation at any time.
Arms & interventions
- DrugMDNA11
MDNA11 will be administered, IV on a once every 2 weeks (Q2W) dosing schedule. Provisional dose cohorts for monotherapy dose escalation doses ranging from 0.003 to 0.6 (mg/kg): until determining the monotherapy Recommended Dose for Expansion (mRDE).
- DrugPembrolizumab (KEYTRUDA®)
MDNA11 will be administered in combination with pembrolizumab, IV. MDNA11 dose range to be evaluated in combination with pembrolizumab until determining the combination Recommended Dose for Expansion (cRDE).
Outcome measures
Primary
MDNA11 Recommended Dose for Expansion for monotherapy (mRDE) and Recommended Dose for Expansion for combination (cRDE)
Evaluation of tolerability as measured by number of patients with dose limiting toxicities (DLTs)
Time frame: 24 months
Incidence of Treatment Related Adverse Events (TRAEs)
Rate of TRAEs in patients with advanced solid tumors
Time frame: 24 months
Incidence of Treatment Emergent Adverse Events (TEAEs)
Rate of TEAEs in patients with advanced solid tumors
Time frame: 24 months
Secondary
Pharmacokinetic characteristics on MDNA11 - Cmax (ug/mL)
Time frame: Up to 24 months
Pharmacokinetic characteristics on MDNA11 - Tmax (h)
Time frame: Up to 24 months
Pharmacokinetic characteristics on MDNA11 - AUClast (h.ug/mL)
Time frame: Up to 24 months
Immunogenicity of MDNA11 (anti-drug antibodies)
Time frame: Up to 24 months
Pharmacodynamic effects of MDNA11
Time frame: Up to 24 months
Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Overall Response Rate (ORR)
Time frame: Approximately 24 months
Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Disease Control Rate (DCR)
Time frame: Approximately 24 months
Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Progression Free Survival (PFS)
Time frame: Approximately 24 months
Eligibility criteria
Study locations (7)
Sharp Memorial Hospital
San Diego, California, 92123
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158
Providence Saint John's Health Center
Santa Monica, California, 90404
Boca Raton Regional Hospital
Boca Raton, Florida, 33486
Emory - Winship Cancer Institute
Atlanta, Georgia, 30322
Karmanos Cancer Institute
Detroit, Michigan, 48201
MD Anderson Cancer Center
Houston, Texas, 77030