MDNA11: 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).
Pembrolizumab (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).
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Key Inclusion Criteria:
1. Aged at least 18 years (inclusive at the time of informed consent).
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
3. 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.
4. Histologically or cytologically confirmed locally advanced or metastatic solid tumor (see tumor types listed under conditions)
5. Demonstrated adequate organ function
6. Measurable disease as per Response Evaluation Criteria in Solid Tumors, (RECIST v1.1) and documented by CT and/or MRI.
7. Life expectancy of ≥ 12 weeks.
8. 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.
9. Agree to use highly effective contraception methods. WOCBP must agree to use highly effective birth control.
Key Exclusion Criteria:
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.
2. 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.
3. Active malignancy (other than the disease under treatment in the study) within the previous 3 years except for curable cancers.
4. 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.
5. Clinically significant active, known or suspected autoimmune disease, or diseases that can be exacerbated with immunotherapy.
6. Severe pulmonary, cardiac or other systemic disease.
7. Known hepatitis B or C virus infection.
8. Females who are pregnant or lactating or planning to become pregnant during the study.
9. Has had an allogeneic tissue/solid organ transplant.
10. Active infection requiring systemic therapy.
11. Any medical, emotional or psychiatric condition that interfere with the patient's ability to adhere to the protocol
12. 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.
13. Known severe hypersensitivity to any component of study drug(s).
14. Inability to comply with study and follow up procedures as judged by the Investigator.
Primary outcome measure(s)
MDNA11 Recommended Dose for Expansion for monotherapy (mRDE) and Recommended Dose for Expansion for combination (cRDE) — 24 months Evaluation of tolerability as measured by number of patients with dose limiting toxicities (DLTs)
Incidence of Treatment Related Adverse Events (TRAEs) — 24 months Rate of TRAEs in patients with advanced solid tumors
Incidence of Treatment Emergent Adverse Events (TEAEs) — 24 months Rate of TEAEs in patients with advanced solid tumors
Trial sites (27)
Facility
City
Region
Status
Sharp Memorial Hospital
San Diego
California
Recruiting
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco
California
Active Not Recruiting
Providence Saint John's Health Center
Santa Monica
California
Recruiting
Boca Raton Regional Hospital
Boca Raton
Florida
Recruiting
Emory - Winship Cancer Institute
Atlanta
Georgia
Recruiting
Karmanos Cancer Institute
Detroit
Michigan
Recruiting
MD Anderson Cancer Center
Houston
Texas
Active Not Recruiting
Scientia Clinical Research
Randwick
New South Wales
Recruiting
Macquarie University
Sydney
New South Wales
Recruiting
University of the Sunshine Coast
Buderim
Queensland
Recruiting
Gallipoli Medical Research Foundation
Greenslopes
Queensland
Recruiting
Princess Margaret Cancer Center
Toronto
Ontario
Recruiting
Mater Misericordiae University Hospital
Dublin
Ireland
Recruiting
START Lisbon - Centro de Ensaios Clínicos, ULS Sta Maria
Lisbon
Portugal
Recruiting
Instituto Portugues De Oncologia Do Porto
Porto
Portugal
Recruiting
Samsung Medical Center
Seoul
Gangnam-gu
Active Not Recruiting
Seoul National University Bundang Hospital
Seongnam-si
Gyeonggi-do
Active Not Recruiting
The Catholic University of Korea St. Vincent Hospital
Suwon
Gyeonggi-do
Active Not Recruiting
Seoul National University Hospital
Seoul
Jongno-gu
Active Not Recruiting
Institut Catala d'Oncologia (ICO)-Badalona
Badalona
Spain
Recruiting
START Barcelona / HM Nou Delfos
Barcelona
Spain
Recruiting
Hospital de la Santa Creu i Sant Pau
Barcelona
Spain
Recruiting
Hospital Universitario Ramón y Cajal
Madrid
Spain
Recruiting
START Madrid / Hospital Universitario Fundacion Jimenez Diaz
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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