A Dose Escalation/Expansion Study of MDK-703 in Patients With Advanced or Metastatic Solid Tumors (ORCHID-1)

A Phase 1/2, Open-Label, Multicenter Study of MDK-703 as a Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With Advanced or Metastatic Solid Tumors (ORCHID-1)

This is an open-label, dose escalation and dose expansion study of MDK-703 as a monotherapy and in combination with other cancer therapies in adult study participants with advanced or metastatic solid tumors.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: MDK-703; Drug: Checkpoint Inhibitor, Immune

Detailed Description

This is a Phase 1/2, open-label, multicenter, dose escalation and dose expansion study evaluating MDK-703 in adult study participants with advanced or metastatic solid tumors. This study will initially commence with dose escalation to evaluate the safety/tolerability of MDK-703 as a monotherapy and in combination with other cancer therapies. Once the monotherapy and/or combination therapy maximum tolerated dose (MTD), optimal biological dose (OBD), and/or recommended dose (RD) has been determined, then dose expansion of MDK-703 may commence in select populations of interest. The study will also evaluate the anti-tumor activity and pharmacokinetic (PK) and pharmacodynamic (PD) profiles of MDK-703 as a monotherapy and in combination with other cancer therapies.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Sarah Cannon Research Institute (Florida Cancer Specialists)
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute
  • Texas
    • Austin, Texas, United States, 78758
      • NEXT Oncology Austin
    • Dallas, Texas, United States, 75251
      • Mary Crowley Cancer Research
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Oncology Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Measurable disease per RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate cardiovascular, hematological, liver, and renal function.
• Prior anti-cancer therapy is allowed as long as any treatment related toxicity is resolved to an appropriate level.
• Females of childbearing potential and men who are not surgically sterile must agree to use medically-accepted method of birth control during the study.
• [Females] Negative serum pregnancy test within 14 days prior to initiating study treatment.
• [Males] Agreement to refrain from donating or banking sperm during the treatment period.

Exclusion Criteria:

• Treated with anti-cancer therapy or an investigational agent within 2 weeks or 5 half-lives prior to first dose, whichever is shorter; or within 4 weeks for immunotherapy.
• Unresolved toxicities from prior systemic therapy greater than NCI CTCAE grade 1 at time of first dose, except alopecia, vitiligo, and grade 2 neuropathy due to prior chemotherapy.
• Radiotherapy within 14 days prior to first dose of study drug.
• Major surgery within 30 days prior to first dose of study drug, or anticipation of major surgery during study treatment.
• Active autoimmune disease requiring systemic treatment within the past 3 months or have a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents.
• Primary central nervous system (CNS) disease or leptomeningeal disease.
• Impaired cardiovascular function or clinically significant cardiovascular disease.
• Uncontrolled diabetes mellitus or other uncontrolled immune-related endocrinopathies.
• Abnormal pulmonary function within the previous 6 months, including history of pneumonitis, active pneumonitis, interstitial lung disease requiring the use of steroids, idiopathic pulmonary fibrosis, active pleural effusion, severe dyspnea at rest or requiring supplementary oxygen therapy.
• History of allogenic, bone marrow, or solid organ transplant.
• History of cerebrovascular events within 6 months prior to first dose.
• Human immunodeficiency virus (HIV) infection or active infection with hepatitis C; uncontrolled hepatitis B infection.
• Clinically significant bleeding within 2 weeks prior to first dose (e.g., gastrointestinal bleeding, intracranial hemorrhage).
• Prior diagnosis of pulmonary embolism within 3 months prior to first dose.
• Known intolerance, hypersensitivity, or contraindication to any components of MDK-703 or checkpoint inhibitors for applicable cohorts.
• History of other malignancy within 5 years prior to first dose, except for patients who are disease-free for >2 years after treatment with curative intent or who have carcinoma in situ which has been excised.
• Any serious medical condition (including pre-existing autoimmune disease or inflammatory disorder), laboratory abnormality, psychiatric condition, or any other significant or unstable concurrent medical illness that in the opinion of the Investigator would preclude protocol therapy or would make the subject inappropriate for the study.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MDK-703 Monotherapy; MDK-703 will be administered in sequential ascending doses as a monotherapy until unacceptable toxicity, disease progression, or withdrawal of consent.	Drug: MDK-703; MDK-703 will be administered as specified under Arm description.
Experimental: MDK-703 in combination with a checkpoint inhibitor; MDK-703 will be administered in sequential ascending doses in combination with a checkpoint inhibitor until unacceptable toxicity, disease progression, or withdrawal of consent.	Drug: MDK-703; MDK-703 will be administered as specified under Arm description.; Drug: Checkpoint Inhibitor, Immune; Checkpoint inhibitor will be administered as specified under Arm description.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicities (DLT)	Based on toxicities observed from time of first dose through first cycle of treatment	Assessed up to 24 months
Maximum tolerated dose (MTD)	Based on toxicities observed	Assessed up to 24 months
Optimal biological dose (OBD)	Based on toxicities observed	Assessed up to 24 months
Recommended dose (RD)	Based on toxicities observed	Assessed up to 24 months
Adverse events (AE)	Incidence and severity of treatment-emergent AEs and serious AEs as assessed by CTCAE v5.0	Assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months
Duration of Response (DOR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months
Time to Response (TTR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months
Disease Control Rate (DCR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months
Progression-Free Survival (PFS)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months
Overall Survival (OS)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months
Blood concentration of MDK-703	Blood concentration of MDK-703 at various timepoints	Assessed up to 24 months
Time to achieve maximum blood concentration	Time to achieve maximum blood concentration of MDK-703	Assessed up to 24 months

Collaborators and Investigators

• Sponsor: Medikine, Inc.
• Investigators: Study Director: Joseph Leveque, MD, Chief Medical Officer

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: January 19, 2023
• First Submitted That Met QC Criteria: February 6, 2023
• First Posted (Actual): February 8, 2023

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: breast cancer; immunotherapy; oncology; prostate cancer; ovarian cancer; pancreatic cancer; solid tumor; neoplasms; advanced solid tumor; metastatic solid tumor; solid malignancies; immuno-oncology; PDAC; MSS-CRC; Interleukin-7; Interleukin 7; MDK-703; IL-7; IL7; microsatellite stable CRC; microsatellite stable colorectal cancer; immune cold
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors
• Other Study ID Numbers: MDK-703-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No