A Phase I/II 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 The ABILITY (A Beta-only IL-2 ImmunoTherapY) study
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Study Summary
To evaluate safety and tolerability, pharmacokinetics, pharmacodynamic, and early signal of anti-tumor activity of MDNA11 alone or in combination with a checkpoint inhibitor in patients with advanced solid tumors To evaluate the safety, efficacy, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of various doses of intravenously administered MDNA11 in patients with advanced solid tumors To establish the recommended dose and treatment schedule To assess the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity of various doses of intravenously administered MDNA11 in patients with advanced, relapsed, or refractory solid tumors The trial includes an MDNA11 monotherapy arm, as well as a combination arm designed to evaluate MDNA11 with KEYTRUDA® (pembrolizumab). To determine the safety and tolerability, define the recommended phase-2 dose (RP2D), and To assess preliminary tumor response of MDNA11 in patients with advanced solid tumors. To evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD) effects, and preliminary clinical activity of MDNA11 as monotherapy and in combination with an immune checkpoint inhibitor in patients with advanced solid tumors To assess MDNA11’s safety, tolerability, PK, PD, and anti-tumor activity to inform on the RDE in an all-comer solid tumor population with advanced cancers refractory to prior systemic therapies. A total of six dose escalation cohorts (MDNA11 dose ranging from 3 ug/kg to 120 ug/kg) were evaluated, with the majority of patients (73%) having also received at least one prior line of immunotherapy with or without primary resistance to immune checkpoint inhibitors. To evaluate the safety, pharmacokinetic (PK), pharmacodynamic (PD) and preliminary clinical activity of MDNA11 as monotherapy and in combination with Prembrolizumab in pre-treated patients with advanced solid tumors. To determine the recommended dose for expansion (RDE). To assess the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity of various doses of intravenously administered MDNA11 in patients with advanced, relapsed, or refractory solid tumors and includes an MDNA11 monotherapy arm, as well as a combination arm designed to evaluate MDNA11 in combination with pembrolizumab (KEYTRUDA®). To assess the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of MDNA11 as monotherapy or in combination with pembrolizumab (KEYTRUDA®). In the combination dose escalation of the Phase 2 study, approximately 12 patients are expected to be enrolled and administered ascending doses of MDNA11 intravenously once every two weeks in combination with pembrolizumab. This portion of the study includes patients with a wide range of solid tumors with the potential for susceptibility to immune modulating therapeutics. Upon identification of an appropriate dose regimen for combination, the study will proceed to a combination dose expansion cohort. To evaluate MDNA11, a long-acting ‘beta-enhanced not-alpha’ interleukin-2 (IL-2) super-agonist, as monotherapy or in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in patients with advanced solid tumors
- Aged at least 18 years (inclusive at the time of informed consent).
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
- Must be able and willing to provide written informed consent prior to start of any study procedures and assessments and must be willing to comply with all study procedures.
- Histologically or cytologically confirmed locally advanced or metastatic solid tumor that is unresectable (see tumor types listed under conditions)
- Demonstrated adequate organ function
- Measurable disease as per Response Evaluation Criteria in Solid Tumors, (RECIST v1.1) and documented by CT and/or MRI.
- Life expectancy of = 12 weeks.
- Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and within 72 hours before the first dose of study drug(s). Women must not be breastfeeding.
- Agree to use highly effective contraception methods. WOCBP must agree to use highly effective birth control
- key eligibility criteria are locally advanced or metastatic unresectable solid tumors with no more than 4 prior lines of therapy and measurable disease per RECIST v1.1
- Last administration of prior antitumor therapy:
- Prior systemic anti-cancer therapy including investigational agents within 4 weeks (could consider shorter interval for kinase inhibitors or other short half-life drugs) prior to start of treatment.
- Prior radiotherapy within 2 weeks prior to start of treatment or has had a history of radiation pneumonitis. A 1-week washout is required for palliative radiation (<2 weeks of radiotherapy) to non-CNS disease.
- Radiation therapy to the lung that is > 30Gy within 6 months prior to start of treatment.
- Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to start of treatment. Concomitant participation in an observational study must be discussed on a case-by-case basis with the MM for approval.
- Has known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to start of treatment, subject to discussion with MM.
- Active malignancy (other than the disease under treatment in the study) within the previous 3 years except for curable cancers.
- Condition requiring long-term systemic treatment with either corticosteroids > 10 mg daily prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to start of treatment.
- Clinically significant active, known or suspected autoimmune disease, or diseases that can be exacerbated with immunotherapy.
- Severe pulmonary, cardiac or other systemic disease.
- Known hepatitis B or C virus infection.
- Females who are pregnant or lactating or planning to become pregnant during the study.
- Has had an allogeneic tissue/solid organ transplant.
- Active infection requiring systemic therapy.
- Any medical, emotional or psychiatric condition that interfere with the patient's ability to adhere to the protocol
- Any other underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug(s) unsafe or obscure the interpretation of toxicity determination or adverse events.
- Known severe hypersensitivity to any component of study drug(s).
- Inability to comply with study and follow up procedures as judged by the Investigator.
Clinical Study Information for Healthcare Providers
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