GM103 Intratumoral Injection in Patients With Locally Advanced, Unresectable, Refractory and/or Metastatic Solid Tumors

Breast Cancer Clinical Trial

Official title:

A Phase I/II, Open-label, Dose-escalation With Expansion Study of GM103 Via Intratumoral Injection, Alone and in Combination With Pembrolizumab in Adult Patients With Locally Advanced, Unresectable, Refractory and/or Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06265025
• Other study ID #: GM103-CT-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 20, 2024
• Est. completion date: October 30, 2028

Study information

• Verified date: March 2024
• Source: GeneMedicine Co., Ltd.
• Contact: KyoungRyun Park
• Phone: +82 2 6214 3247
• Email: krpark[@]gene-medicine.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to measure safety, tolerability, and preliminary antitumor efficacy of GM103 administered alone and in combination with pembrolizumab in patients with locally advanced, unresectable, refractory and/or metastatic solid tumors (including but not limited to head and neck cancer, malignant melanoma, CRC, renal cell carcinoma, cervical cancer, and breast cancer). Study details include:

Description:

Part A, B - Primary Objectives - To determine the MTD and RP2D based on safety and tolerability of GM103 as monotherapy. - To evaluate overall safety profile of GM103 as monotherapy. - Secondary Objectives - To assess preliminary anti-tumor efficacy of GM103 at the RP2D, as monotherapy. Part C - Primary Objectives - To determine the MTD and RP2D based on safety and tolerability of GM103 in combination with pembrolizumab. - To evaluate overall safety profile of GM103 in combination with pembrolizumab . - Secondary Objectives - To assess preliminary anti-tumor efficacy of GM103 at the RP2D, in combination with pembrolizumab.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 125
• Est. completion date: October 30, 2028
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patient must be 18 years of age or over, at the time of signing the informed consent.

2. Have a diagnosis of locally advanced, unresectable, refractory and/or metastatic solid tumors

3. Have a tumor that is accessible and is willing to consent to tumor biopsies during the study.

4. Have at least one measurable site of disease according to RECIST 1.1 criteria; The lesions should be either previously non irradiated or progressive lesions after irradiation, that can be accurately measured at baseline (for measurable lesions) with computed tomography (CT) or magnetic resonance imaging (MRI).

5. Part A, B and C: Have at least one intratumorally injectable lesion (measurable and/or non-measurable based on RECIST 1.1), that can be accurately measured at baseline (for measurable lesions) with computed tomography (CT) or magnetic resonance imaging (MRI) or positron emission tomography-computed tomography (PET-CT); or clinical examination and which is suitable for repeated measurement.

6. Part B and C (only for dose expansion cohort): Have paired pre- and on treatment tumor biopsies for patients with metastases that are safely accessible as determined by the investigator.

7. Patients with brain metastasis must have stable disease and must be neurologically asymptomatic and not requiring corticosteroid treatment.

8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

9. Have a predicted life expectancy of 12 weeks or more.

10. Able to comply with study procedures in the Investigator's opinion.

11. Adequate organ function determined within 4 weeks prior to screening

12. Patient is male or female.

13. Contraceptive use by women must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

14. Patient is capable of giving signed informed consent.

Exclusion Criteria:

1. Known history or eiciency virus [HIV]/acquired immunodeficiency syndrome [AIDS]) and/or medication.

2. Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisolone equivalent) or other immunosuppressive medications within 14 days of the first dose of study treatment.

3. Patients with a history of, or active, known or suspected auto-immune disease or a syndrome that requires systemic or immunosuppressive agents.

4. Active infections requiring antibiotics, physician monitoring or recurrent fevers (>38.0 °C) associated with a clinical diagnosis of active infection.

5. Patient who has a history of seizures, central nervous system abnormalities, mental disorders, and heart disease.

6. Patient who has a history of pleural effusion, pulmonary embolism, and intestinal obstruction.

7. Treatment with any systemic anticancer therapies for locally advanced or metastatic within 4 weeks or 6 half-lives of prior anticancer therapy, whichever is shorter, prior to initiation of study treatment.

8. Previous treated with GM103 or other oncolytic viruses.

9. Radiation therapy within 2 weeks prior to enrollment.

10. Use of the antiviral agents within 7 days prior to the first dose of study treatment; or pegylated interferon in the 14 days before the first dose of study treatment

11. Patients who have received a live vaccine within 30 days of study enrollment.

12. Any serious or uncontrolled medical disorder that, in the opinion of the Investigator or the Medical Monitor, may increase the risk associated with study participation or study treatment administration, impair the ability of the patient to receive protocol therapy or interfere with the interpretation of study results.

13. Participation of any other clinical trials within 4 weeks prior to first administration of study treatment.

14. Administration of an investigational drug in the 28 days before the first dose of study treatment.

15. Has an ejection fraction (EF) of 50% or less, based on a multigated acquisition (MUGA) scan or echocardiogram (ECHO).

16. Major surgery within 4 weeks prior to enrollment.

17. Inability or unwillingness to follow study procedures including drug administration.

18. Any serious medical condition or abnormality in clinical laboratory tests

Related Conditions & MeSH terms

• Breast Cancer
• Carcinoma, Renal Cell
• Cervical Cancer
• Colorectal Cancer
• Head and Neck Cancer
• Malignant Melanoma
• Melanoma
• Renal Cell Carcinoma

Intervention

Drug:
• GM103 (Part A)
dose escalation of GM103 as monotherapy, conducted in 12-24 patients. Part A will include a screening period of up to 28 days, a dose limiting toxicity (DLT) evaluation period of the first 2 cycles, and a treatment period from cycles 3-12 (each cycle will consist of 14 days [2 weeks]).
• GM103 (Part B)
dose expansion study of GM103 as monotherapy, conducted in up to 40 patients (a minimum of 20 patients per target disease [HNC, CRC]). Part B of the study will include a screening period of up to 28 days, and 1 to a maximum of 12 treatment cycles (each cycle will consist of 14 days [2 weeks]).
• GM103 and Pembrolizumab (Part C)
dose-escalation and dose-expansion of GM103 in combination with pembrolizumab, conducted in approximately 61 patients. Part C of the study will include a screening period of up to 28 days, a safety run-in period of 2 cycles (it consists of 2 cohorts and the first 1 cycle for the DLT assessment period of each cohort is included, each cycle will consist of 21 days [3 weeks]), and a dose expansion period from cycle 3 to a maximum of 12 treatment cycles (of 21 days [3 weeks]).

Locations

Country	Name	City	State
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Hanyang University Seoul Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
GeneMedicine Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with DLTs by cohorts	To determine the MTD and RP2D based on safety and tolerability of GM103 as monotherapy (Parts A, B).	during the first 28 days of treatment
Primary	Percentage of patients with DLTs	To determine the MTD and RP2D based on safety and tolerability of GM103 in combination with pembrolizumab (Part C)	during the first 21 days of treatment
Primary	Incidence of AEs, AESIs, SAEs, AEs leading to discontinuation, and AEs resulting in death	To evaluate overall safety profile of GM103 as monotherapy (Parts A, B) and in combination with pembrolizumab (Part C)	through study completion, and average 1 year
Secondary	ORR	To assess preliminary anti-tumor efficacy of GM103 at the RP2D, as monotherapy (Parts A and B); To assess preliminary anti-tumor efficacy of GM103 at the RP2D, in combination with pembrolizumab (Part C)	through study completion, and average 1 year
Secondary	DCR defined as the proportion of patients whose BOR was CR, PR and SD	To assess preliminary anti-tumor efficacy of GM103 at the RP2D, as monotherapy (Parts A and B); To assess preliminary anti-tumor efficacy of GM103 at the RP2D, in combination with pembrolizumab (Part C)	through study completion, an average of 1 year
Secondary	Median PFS defined as the time from the date of the first administration of study drug to the date of disease progression or death	To assess preliminary anti-tumor efficacy of GM103 at the RP2D, as monotherapy (Parts A and B); To assess preliminary anti-tumor efficacy of GM103 at the RP2D, in combination with pembrolizumab (Part C)	through study completion, an average of 1 year
Secondary	Incidence of GM103 detection	To assess preliminary anti-tumor efficacy of GM103 at the RP2D, as monotherapy (Parts A and B); To assess preliminary anti-tumor efficacy of GM103 at the RP2D, in combination with pembrolizumab (Part C)	every cycle, through study completion, an average of 1 year [up to 12 treatment cycles, Part A&B: each cycle will consist of 14 days(2 weeks) / Part C: each cycle will consist of 21 days(3 weeks)]
Secondary	Changes in the level of anti-adenovirus antibodies(ADA) in blood compared to baseline (ADA in genome copies/mL using qPCR)	To assess preliminary anti-tumor efficacy of GM103 at the RP2D, as monotherapy (Parts A and B); To assess preliminary anti-tumor efficacy of GM103 at the RP2D, in combination with pembrolizumab (Part C)	every 2 cycles after the first cycle, through study completion, an average of 1 year [up to 12 treatment cycles, Part A&B: each cycle will consist of 14 days(2 weeks) / Part C: each cycle will consist of 21 days(3 weeks)]