This is a multipart, open-label, multi-center dose escalation, dose expansion phase I clinical trial designed to evaluate the safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), and preliminary efficacy of MEM-288 in patients with advanced solid tumors. Eligible subjects must have a tumor lesion(s) which is accessible for injection.
The dose escalation phase (Part 1A - advanced solid tumors) has completed and is closed to enrollment. This phase evaluated multiple doses of MEM-288 dosed via intratumoral injection once every 3 weeks to assess safety, tolerability, preliminary efficacy, and to determine the MTD.
The dose expansion phase has multiple parts for advanced NSCLC. Part 1B has completed after evaluation of MEM-288 dosed via intratumoral injection in combination with standard of care nivolumab dosed via intravenous injection.
In a separate dose expansion arm (Part 1C) that is open for enrollment, patients with advanced NSCLC will be randomized to receive either an initial priming dose of MEM-288 injected into an accessible lesion (s) alone (Day 1) followed by MEM-288 in combination with standard of care docetaxel every 3 weeks up to 6 doses or MEM-288 injected into an accessible lesion(s) in combination with standard of care docetaxel therapy Day 1 and every 3 weeks up to 6 doses.
The study rationale is that the oncolytic effect of MEM-288 combined with the presence of CD40L and type 1 IFN in injected tumors will provide a strong signal for DC-mediated T cell activation leading to generation of systemic anti-tumor T cell responses with broad specificity akin to what is observed in the abscopal effect.
Ability to understand and provide informed consent.
Willingness and ability to comply with scheduled study visits and procedures.
Adult men or women age ≥ 18 years.
ECOG performance status of 0 or 1.
Pregnant or breast feeding.
Serious uncontrolled medical disorder, psychiatric condition or laboratory abnormalities that, in the opinion of the investigator, may increase the risk associated with study participation or may interfere with the interpretation of study results.
Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic), or significant traumatic injury, within 4 weeks prior to starting study treatment or has not recovered from side effects of such procedure. Video-assisted thoracic surgery (VATS) and mediastinoscopy are exceptions and patients can receive study treatment ≥1 week after these procedures.
History of clinically significant noninfectious interstitial pneumonitis (i.e., limiting activities of daily living or requiring therapeutic intervention), including clinically significant radiation pneumonitis.
Single group
MEM-288 Intratumoral Injection
Biological/VaccineIntratumoral injection of MEM-288, conditionally replicative oncolytic adenovirus vector encoding transgenes for human interferon beta (IFNβ) and a recombinant chimeric form of CD40-ligand (MEM40).
Nivolumab
Biological/Vaccineanti-PD1 monoclonal antibody
Docetaxel
Drug75 mg/m2 intravenous administration every 3 weeks
Part 1A Monotherapy: Maximum Tolerated Dose (MTD)
MTD is defined as the highest dose with ≤ 17% dose limiting toxicity (DLT) rate.
Safety and Tolerability assessed by Adverse Events (AEs)
An adverse event (AE) is any untoward medical occurrence in a subject receiving study drug and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended or worsening sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not related to use of the study drug.
Overall Response Rate (ORR)
ORR measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Disease Control Rate (DCR)
DCR measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Progression Free Survival (PFS)
To determine the PFS days post treatment initiation.
Overall Survival (OS)
To determine the survival days post treatment initiation.
Exploratory Biomarker Analysis
Analysis of potential associations between biomarker measures and anti-tumor activity, immunogenicity, and immune-activation assessments.
Click on the lead sponsor to view all of their trials.
Memgen, Inc.
Lead sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborator
Duke Cancer Institute
Collaborator
