Fallopian Tube Cancer, Ovarian Carcinoma, Peritoneal Carcinoma
Conditions
Brief summary
This is a multicenter, open-label, single arm phase I study evaluating the safety and tolerability as well as some activity parameters of TG4050 in patients with ovarian, fallopian or peritoneal serous carcinoma.
Interventions
DRUGTG4050
Subcutaneous injections weekly for the first 6 weeks and then every 3 weeks.
Sponsors
Transgene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed written informed consent. 2. Female patients ≥ 18 years 3. Histologically confirmed high grade, advanced stage serous ovarian, fallopian tube or primary peritoneal carcinoma. 4. Patients who have undergone primary debulking surgery or interval debulking surgery and have completed standard first-line platinum-based chemotherapy and for whom tumor tissue has been banked. 5. Patients must have achieved a complete response to therapy 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at treatment period initiation 7. Adequate hematological, hepatic and renal functions.
Exclusion criteria
1. Patient having received any cancer immunotherapy including cancer vaccines, any antibody/drug targeting T cell co-regulatory proteins such as anti-Programmed cell death 1 (anti-PD1), anti-Programmed death-ligand 1 (anti-PDL1) or anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTL4) 2. Patients with other active malignancy ≤ 3 years prior to registration except non-melanoma skin cancer, stage 0 in situ carcinoma. 3. Patient post-organ transplantation, including allogeneic stem cell or bone marrow transplantation. 4. Known history of positive testing for Human Immunodeficiency Virus (HIV) or known AIDS (Acquired Immune Deficiency Syndrome). 5. Any known allergy or reaction to eggs or attributed to compounds of similar chemical or biological composition to therapeutic vaccines/immunotherapeutic products. 6. Acute or chronic infection with hepatitis C Virus (HCV) or Hepatitis B Virus (HBV). 7. Major surgery within 4 weeks of treatment start. 8. Treatment with another investigation agent within 30 days prior to TG4050 treatment initiation. 9. Patients under chronic treatment with systemic corticosteroids or other immunosuppressive drugs . Steroids with no or minimal systemic effect (topical, inhalation) are allowed. 10. Use of live vaccine for the prevention of infectious diseases during the four-week period prior to TG4050 treatment initiation planned date. Furthermore, patients should not receive any live vaccine during the period of study treatment administration. 11. Uncontrolled intercurrent illness.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability (Adverse Event Reported Per CTCAE v5) | Up to 1 year . Adverse events were collected from treatment initiation weekly for the first six weeks, every three weeks thereafter until 30 days after the last treatment administration. | Incidence of Adverse Events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CA-125 Response According to GCIC | Up to 1 year. CA-125 response assessment every 3 weeks from the start of study treatment until treatment discontinuation. | Percentage of patients with a minimum 50% reduction in CA-125 serum levels lasting for 28 days relative to pre-treatment CA-125 (Carbohydrate Antigen 125) serum level per the GCIC criteria (the Gynecological Cancer Intergroup). |
| Tumor Response According to RECIST 1.1 | Starting on Day 43 and then every nine weeks thereafter, until disease progression (estimated 12 months). | Best overall response according to RECIST 1.1 was assessed for all patients, defined as follows: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. |
| Time to Measurable Relapse/Progression Per RECIST 1.1 | 43 days after treatment, and thereafter every 9 weeks until disease progression or relapse (estimated 12 months). | Time to measurable relapse/progression per RECIST 1.1 (months) is defined as the time from the date of the first treatment injection until relapse or documented progressive disease, whichever occurs first, as assessed using CT scan or MRI. |
| Failure to Provide Rate | From informed consent (ICF) signature up to baseline. | Percentage of consented participants who could not be enrolled in the TG4050 treatment period due to manufacturing failure. |
Countries
France, United States
Participant flow
Pre-assignment details
A total of 64 patients consented to participate in the study. Of these, 58 (90.6%) were non-included-21 at study entry and 37 at baseline-while 6 patients were assigned to treatment.
Participants by arm
| Arm | Count |
|---|---|
| TG4050 Arm Participants received subcutaneous injections of TG4050 at a dose of 1 × 10⁸ PFU weekly for the first six weeks, and then every three weeks, for up to a maximum of 20 injections.
As only one participant was treated in Cohort A (no measurable disease at treatment initiation), the results are presented by combining both cohorts, for a total of six participants. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | TG4050 Arm | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 5 Participants | — |
| Age, Categorical Between 18 and 65 years | 1 Participants | — |
| Age, Continuous | 73.5 years | — |
| BMI | 29.3 kg/m² STANDARD_DEVIATION 4.79 | — |
| Eastern Cooperative Oncology Group Performance Status (ECOG PS) ECOG status 0 | 5 Participants | — |
| Eastern Cooperative Oncology Group Performance Status (ECOG PS) ECOG status 1 | 1 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment France | 1 participants | — |
| Region of Enrollment United States | 5 participants | — |
| Sex: Female, Male Female | 6 Participants | — |
| Sex: Female, Male Male | 0 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 6 |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
Primary
Safety and Tolerability (Adverse Event Reported Per CTCAE v5)
Incidence of Adverse Events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
Time frame: Up to 1 year . Adverse events were collected from treatment initiation weekly for the first six weeks, every three weeks thereafter until 30 days after the last treatment administration.
Population: Safety Analysis Set (SAF): all patients included and who received at least one dose of TG4050.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TG4050 Arm | Safety and Tolerability (Adverse Event Reported Per CTCAE v5) | Adverse Event | 6 Participants |
| TG4050 Arm | Safety and Tolerability (Adverse Event Reported Per CTCAE v5) | Dose Limiting Toxicity | 0 Participants |
| TG4050 Arm | Safety and Tolerability (Adverse Event Reported Per CTCAE v5) | AE related to TG4050 | 6 Participants |
| TG4050 Arm | Safety and Tolerability (Adverse Event Reported Per CTCAE v5) | Injection site reaction | 6 Participants |
| TG4050 Arm | Safety and Tolerability (Adverse Event Reported Per CTCAE v5) | AE related to other study procedure | 0 Participants |
| TG4050 Arm | Safety and Tolerability (Adverse Event Reported Per CTCAE v5) | AE leading to treatment discontinuation | 1 Participants |
| TG4050 Arm | Safety and Tolerability (Adverse Event Reported Per CTCAE v5) | AE related to TG4050 and leading to treatment discontinuation | 0 Participants |
| TG4050 Arm | Safety and Tolerability (Adverse Event Reported Per CTCAE v5) | Serious Adverse Event | 1 Participants |
| TG4050 Arm | Safety and Tolerability (Adverse Event Reported Per CTCAE v5) | Serious Adverse Event related to TG4050 | 0 Participants |
| TG4050 Arm | Safety and Tolerability (Adverse Event Reported Per CTCAE v5) | Grade 3/4 AE | 0 Participants |
| TG4050 Arm | Safety and Tolerability (Adverse Event Reported Per CTCAE v5) | Fatal AE | 1 Participants |
| TG4050 Arm | Safety and Tolerability (Adverse Event Reported Per CTCAE v5) | Fatal AE related toTG4050 | 0 Participants |
Secondary
CA-125 Response According to GCIC
Percentage of patients with a minimum 50% reduction in CA-125 serum levels lasting for 28 days relative to pre-treatment CA-125 (Carbohydrate Antigen 125) serum level per the GCIC criteria (the Gynecological Cancer Intergroup).
Time frame: Up to 1 year. CA-125 response assessment every 3 weeks from the start of study treatment until treatment discontinuation.
Population: Safety Analysis Set (SAF): all patients who received at least one dose of TG4050
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TG4050 Arm | CA-125 Response According to GCIC | 1 Participants |
Secondary
Failure to Provide Rate
Percentage of consented participants who could not be enrolled in the TG4050 treatment period due to manufacturing failure.
Time frame: From informed consent (ICF) signature up to baseline.
Population: Population of participants at baseline: 37 screen failures and 6 treated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TG4050 Arm | Failure to Provide Rate | 3 Participants |
Secondary
Time to Measurable Relapse/Progression Per RECIST 1.1
Time to measurable relapse/progression per RECIST 1.1 (months) is defined as the time from the date of the first treatment injection until relapse or documented progressive disease, whichever occurs first, as assessed using CT scan or MRI.
Time frame: 43 days after treatment, and thereafter every 9 weeks until disease progression or relapse (estimated 12 months).
Population: Safety Analysis Set (SAF): all patients who received at least one dose of TG4050
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TG4050 Arm | Time to Measurable Relapse/Progression Per RECIST 1.1 | 2.5 months |
Secondary
Tumor Response According to RECIST 1.1
Best overall response according to RECIST 1.1 was assessed for all patients, defined as follows: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time frame: Starting on Day 43 and then every nine weeks thereafter, until disease progression (estimated 12 months).
Population: Safety Analysis Set (SAF): all patients included and who received at least one dose of TG4050.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TG4050 Arm | Tumor Response According to RECIST 1.1 | Stable disease | 3 Participants |
| TG4050 Arm | Tumor Response According to RECIST 1.1 | Progressive disease | 3 Participants |