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

Advanced or Metastatic Solid Tumors Clinical Trial

— ORCHID-1  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05716295
• Other study ID #: MDK-703-102
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: February 8, 2023
• Est. completion date: April 30, 2024

Study information

• Verified date: May 2024
• Source: Medikine, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: April 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• MDK-703
MDK-703 will be administered as specified under Arm description.
• Checkpoint Inhibitor, Immune
Checkpoint inhibitor will be administered as specified under Arm description.

Locations

Country	Name	City	State
United States	NEXT Oncology Austin	Austin	Texas
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	NEXT Oncology Virginia	Fairfax	Virginia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Sarah Cannon Research Institute (Florida Cancer Specialists)	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Medikine, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicities (DLT)	Based on toxicities observed from time of first dose through first cycle of treatment	Assessed up to 24 months
Primary	Maximum tolerated dose (MTD)	Based on toxicities observed	Assessed up to 24 months
Primary	Optimal biological dose (OBD)	Based on toxicities observed	Assessed up to 24 months
Primary	Recommended dose (RD)	Based on toxicities observed	Assessed up to 24 months
Primary	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	Objective Response Rate (ORR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months
Secondary	Duration of Response (DOR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months
Secondary	Time to Response (TTR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months
Secondary	Disease Control Rate (DCR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months
Secondary	Progression-Free Survival (PFS)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months
Secondary	Overall Survival (OS)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months
Secondary	Blood concentration of MDK-703	Blood concentration of MDK-703 at various timepoints	Assessed up to 24 months
Secondary	Time to achieve maximum blood concentration	Time to achieve maximum blood concentration of MDK-703	Assessed up to 24 months