Clinical trial NCT05688605: A Study of MRG003 in the Treatment of Patients With EGFR-positive Advanced or Metastatic Solid Tumors
Official title: An Open-label, Multi-center, Phase I/II Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of MRG003 in Combination With HX008 in Patients With EGFR-positive Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Keywords: MRG003
HX008
Antibody Drug Conjugate (ADC)
EGFR
Solid tumors
Lead sponsor: Shanghai Miracogen Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-18
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG003 in combination with HX008 in patients with EGFR-positive advanced or metastatic solid tumors.

Detailed description: This study consists of two parts: Phase I and Phase II. The objective of this study is to assess the safety and tolerability of MRG003 in combination with HX008 in patients with EGFR-positive advanced or metastatic solid tumors; and to explore the maximum tolerated dose (MTD) and to determine the recommended phase II dose (RP2D) of combination therapy; and to evaluate the preliminary efficacy, pharmacokinetics, and immunogenicity of combination therapy in the targeted study population.

Eligibility criteria: Inclusion Criteria:

1. Willing to sign the informed consent form and follow the requirements specified in the protocol.
2. Aged 18 to 75 (including 18 and 75), both genders.
3. BMI ≥17
4. Life expectancy ≥ 12 weeks.
5. Patients with EGFR-positive advanced or metastatic solid tumors, including non-small cell lung cancer (NSCLC), squamous cell carcinoma of head and neck (SCCHN), and nasopharyngeal carcinoma (NPC).
6. EGFR-positive determined by immunohistochemistry (except NSCLC, SCCHN and NPC).
7. Patients must have measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
8. The score of ECOG for performance status is 0 or 1.
9. No severe cardiac dysfunction.
10. Acceptable liver, renal, and hematologic function.
11. Patients with childbearing potential must use effective contraception during the treatment and for 6 months after the last dose of treatment.

Exclusion Criteria:

1. History of hypersensitivity to any component of the investigational product.
2. Prior treatment with chemotherapy, biological therapy, immunotherapy, radiotherapy, investigational drugs, attenuated live vaccines, immunomodulators, CYP3A4 inhibitors/inducers, antibody-drug conjugates, Received major surgery without complete recovery, etc.
3. Treatment with MMAE/MMAF ADC drugs
4. Central nervous system metastasis.
5. Toxic reaction or abnormal value of laboratory test caused by previous anti-tumor treatment ≥ 2 (CTCAE v5.0)
6. Presence of peripheral neuropathy ≥ Grade 2.
7. Liver function Child Pugh Grade B or Grade C。
8. Pleural and peritoneal effusion or pericardial effusion with clinical symptoms requiring drainage.
9. Poorly controlled systemic diseases (hypertension and hyperglycemia, etc.)
10. Evidence of active infection of hepatitis B, hepatitis C or HIV.
11. Patients with poorly controlled heart diseases
12. History of ophthalmic abnormalities.
13. History of severe skin disease requiring oral or intravenous therapy.
14. History of interstitial pneumonia, radiation pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc.
15. Active, known or suspected autoimmune disease or drug related immune disease or the disease history within the past 2 years.
16. The patient is using immunosuppressant or systemic hormone therapy.
17. Patients with any past arteriovenous bleeding within 3 months or current history of coagulation disorder.
18. Any clinically significant VTE occurred within 6 months.
19. Received allogeneic tissue/solid organ transplantation.
20. Inoculate live vaccine within 30 days before the first dose.
21. Patients with a positive serum pregnancy test or who are breast-feeding or who do not agree to take adequate contraceptive measures during the treatment and for 180 days after the last dose of study treatment.
22. History of other primary malignant tumor diseases.
23. Investigator considers which not suitable to participate in the clinical trial

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Within 21 days after the first dose of the last patient of the MTD group
measure: Recommended Phase II Dose (RP2D)
timeFrame: Baseline to study completion (up to 12 months)
measure: Objective Response Rate (ORR)
timeFrame: Baseline to study completion (up to 12 months)
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Baseline to study completion (up to 12 months)
measure: Disease Control Rate (DCR)
timeFrame: Baseline to study completion (up to 12 months)
measure: Progression Free Survival (PFS)
timeFrame: Baseline to study completion (up to 12 months)
measure: Overall Survival (OS)
timeFrame: Baseline to study completion (up to 12 months)
measure: Immunogenicity (ADA)
timeFrame: Baseline to 90 days after the last dose.
measure: Adverse Events (AEs)
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: Serious Adverse Events (SAEs)
timeFrame: Baseline to 90 days after the last dose of study treatment
measure: PK parameters: concentration-time curve
timeFrame: Baseline to 90 days after the last dose.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
Study officials:
affiliation: Sun Yat-sen University
name: Ruihua Xu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: