A Study of MRG003 in the Treatment of Patients With EGFR-positive Advanced or Metastatic Solid Tumors

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05688605
• Other study ID #: HX008/MRG003-C001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 30, 2022
• Est. completion date: July 2025

Study information

• Verified date: January 2023
• Source: Shanghai Miracogen Inc.
• Contact: Program Director
• Phone: 86-21-61637960
• Email: clinicaltrials[@]miracogen.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: July 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• MRG003+HX008
Administered intravenously

Locations

Country	Name	City	State
China	Hunan Cancer Hospital	Changsha	Hunan
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Miracogen Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	MTD is the highest dose with the proportion of DLT less than 1/3	Within 21 days after the first dose of the last patient of the MTD group
Primary	Recommended Phase II Dose (RP2D)	The dose level of MRG003 recommended for further clinical studies based on assessment of the safety, efficacy and PK data from this study.	Baseline to study completion (up to 12 months)
Primary	Objective Response Rate (ORR)	ORR is defined as the proportions of patients with a complete response (CR) and partial response (PR). ORR will be assessed by investigator according to RECIST v1.1.	Baseline to study completion (up to 12 months)
Secondary	Duration of Response (DOR)	DOR is defined as the duration from the initial recording of objective disease response to the first onset of tumor progression, or death of any cause.	Baseline to study completion (up to 12 months)
Secondary	Disease Control Rate (DCR)	DCR is defined as the proportion of subjects achieving CR, PR, and SD after treatment.	Baseline to study completion (up to 12 months)
Secondary	Progression Free Survival (PFS)	PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause.	Baseline to study completion (up to 12 months)
Secondary	Overall Survival (OS)	OS is defined as the duration from the start of treatment to death of any cause.	Baseline to study completion (up to 12 months)
Secondary	Immunogenicity (ADA)	The proportion of patients with positive ADA results.	Baseline to 90 days after the last dose.
Secondary	Adverse Events (AEs)	Any reaction, side effect, or untoward event that occurs during the course of the clinical trial whether or not the event is considered related to the study drug.	Baseline to 30 days after the last dose of study treatment
Secondary	Serious Adverse Events (SAEs)	Adverse events that are difficult to deal with in clinical drug research	Baseline to 90 days after the last dose of study treatment
Secondary	PK parameters: concentration-time curve	Plot of drug concentration changing with time after drug administration	Baseline to 90 days after the last dose.