Clinical trial NCT05716295: A Dose Escalation/Expansion Study of MDK-703 in Patients With Advanced or Metastatic Solid Tumors
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced or Metastatic Solid Tumors
Keywords: MDK-703
IL-7
Interleukin 7
Interleukin-7
IL7
oncology
immuno-oncology
immunotherapy
solid tumor
advanced solid tumor
metastatic solid tumor
neoplasms
solid malignancies
pancreatic cancer
PDAC
MSS-CRC
microsatellite stable CRC
microsatellite stable colorectal cancer
prostate cancer
breast cancer
ovarian cancer
immune cold
Lead sponsor: Medikine, Inc.
Sponsor class: INDUSTRY
First posted: 2023-02-08
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Multiple ascending dose escalation followed by dose expansion.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLT)
timeFrame: Assessed up to 24 months
measure: Maximum tolerated dose (MTD)
timeFrame: Assessed up to 24 months
measure: Optimal biological dose (OBD)
timeFrame: Assessed up to 24 months
measure: Recommended dose (RD)
timeFrame: Assessed up to 24 months
measure: Adverse events (AE)
timeFrame: Assessed up to 24 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Assessed up to 24 months
measure: Duration of Response (DOR)
timeFrame: Assessed up to 24 months
measure: Time to Response (TTR)
timeFrame: Assessed up to 24 months
measure: Disease Control Rate (DCR)
timeFrame: Assessed up to 24 months
measure: Progression-Free Survival (PFS)
timeFrame: Assessed up to 24 months
measure: Overall Survival (OS)
timeFrame: Assessed up to 24 months
measure: Blood concentration of MDK-703
timeFrame: Assessed up to 24 months
measure: Time to achieve maximum blood concentration
timeFrame: Assessed up to 24 months
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Sarah Cannon Research Institute (Florida Cancer Specialists)
state: Florida
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Austin
country: United States
facility: NEXT Oncology Austin
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology Virginia
state: Virginia
Study officials:
affiliation: Chief Medical Officer
name: Joseph Leveque, MD
role: STUDY_DIRECTOR
References: