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

Phase 1

Recruiting

• Conditions: Renal Cell Carcinoma; Colorectal Cancer; Head and Neck Cancer; Malignant Melanoma; Breast Cancer; Cervical Cancer
• Interventions: Drug: GM103 (Part A); Drug: GM103 (Part B); Drug: GM103 and Pembrolizumab (Part C)

• Registration Number: NCT06265025
• Lead Sponsor: GeneMedicine Co., Ltd.

Brief 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:

Detailed 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.

Study Timeline

• Study First Submitted: 2024-01-23
• Study First Submitted QC: 2024-02-14
• Study Start: 2024-02-20
• Study First Posted: 2024-02-20
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-20
• Last Update Posted: 2024-03-21
• Primary Completion: 2025-05-30
• Study Completion: 2028-10-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 125

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment (GM103): Part A_Dose escalation	GM103 (Part A)	Multiple escalating dose levels of GM103 (1 x 10\^11 vp, 3 x 10\^11 vp, 1 x 10\^12 vp, 3 x 10\^12 vp)
Treatment (GM103): Part B_Dose expansion	GM103 (Part B)	Dose expansion study of GM103 as monotherapy (GM103 RP2D for HNC, GM103 RP2D for CRC)
Treatment (GM103 and pembrolizumab): Part C_Dose escalation and dose expansion	GM103 and Pembrolizumab (Part C)	Dose-escalation and dose-expansion of GM103 in combination with pembrolizumab * Safety run in cohorts (GM103 1 dose level below RP2D + Pembrolizumab 200mg, GM103 RP2D + Pembrolizumab 200mg) * Dose expansion (GM103 RP2D\*+ Pembrolizumab 200mg for HNC, GM103 RP2D\* + Pembrolizumab 200mg for CRC) * \*Recommended dose based on previous safety run in cohorts

Primary Outcome Measures

Name	Time	Method
Percentage of patients with DLTs by cohorts	during the first 28 days of treatment	To determine the MTD and RP2D based on safety and tolerability of GM103 as monotherapy (Parts A, B).
Percentage of patients with DLTs	during the first 21 days of treatment	To determine the MTD and RP2D based on safety and tolerability of GM103 in combination with pembrolizumab (Part C)
Incidence of AEs, AESIs, SAEs, AEs leading to discontinuation, and AEs resulting in death	through study completion, and average 1 year	To evaluate overall safety profile of GM103 as monotherapy (Parts A, B) and in combination with pembrolizumab (Part C)

Secondary Outcome Measures

Name	Time	Method
ORR	through study completion, and average 1 year	* 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)
DCR defined as the proportion of patients whose BOR was CR, PR and SD	through study completion, an average of 1 year	* 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)
Median PFS defined as the time from the date of the first administration of study drug to the date of disease progression or death	through study completion, an average of 1 year	* 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)
Incidence of GM103 detection	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)]	* 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)
Changes in the level of anti-adenovirus antibodies(ADA) in blood compared to baseline (ADA in genome copies/mL using qPCR)	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)]	* 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)

Trial Locations

Locations (4)

National Cancer Center; 🇰🇷 Goyang-si, Gyeonggi-do, Korea, Republic of

Korea University Anam Hospital; 🇰🇷 Seoul, Korea, Republic of

Hanyang University Seoul Hospital; 🇰🇷 Seoul, Korea, Republic of

Severance Hospital, Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of