Superficial, Palpable, Unresectable/Metastatic Solid Tumour
Conditions
Brief summary
This study will evaluate if AGI-134 given alone is safe and tolerate in treating patients with unresectable/metastatic solid tumours.
Detailed description
Study AGI-134.FIM.101 was a Phase I/IIa, first in man (FIM), multi-center, single-arm, open-label study, designed to evaluate the safety and tolerability of escalating doses of AGI-134 as a monotherapy in unresectable/metastatic solid tumors. The study comprised of 2 parts: Part 1 was an accelerated escalation of the AGI-134 dose, designed to assess the safety and tolerability of AGI-134, as well as to determine the MTD (maximum tolerated dose) and recommended dose for Part 2 of the study (RP2D). Part 2 was designed to assess the safety, tolerability and biological activity of AGI-134 at the RP2D in subjects with either deep or superficial unresectable/metastatic solid tumors.
Interventions
DRUGAGI-134
AGI-134 via IT injection. The proposed treatment is one dose of AGI-134 monotherapy per cycle; each cycle consists in three weeks, dosing will be given for 4 cycles.
Sponsors
Agalimmune Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part 1 (Accelerated escalation): An accelerated escalation dose study designed to assess the safety and tolerability of escalating doses of AGI-134, as well as the Maximum Tolerated Dose (MTD) and the Part 2 dose (RP2D). Part 2: This part of the study was designed to assess the safety, tolerability and anti-tumour activity of AGI-134 as a monotherapy
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult male or female aged 18 years old or older. 2. Have a histologically or cytologically confirmed unresectable metastatic solid tumour and who have received or been intolerant to all curative treatment options and treatments demonstrated to prolong survival. 3. Subjects should have at least two measurable lesions based on RECIST v1.1 as determined by the site study team. 4. Subjects who are willing to undergo tumour biopsies, unless tumour is considered inaccessible or biopsy is otherwise considered not in the subject's best interest. 5. With sufficient tumour size for IT injection 6. Has ≥ 2 lesions: Has ≥1 injectable lesion which is amenable to injection and biopsy and is measurable according to RECIST v1.1. Has ≥1 metastatic lesion is amenable for biopsy and measurable according to RECIST v1.1 7. Evaluable Disease according to RECIST v1.1 8. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. 9. Has a life expectancy \>3 months 10. Adequate organ function 11. Women of childbearing potential and all men must agree to use 2 methods of an adequate contraception 12. Subject is able and willing to comply with the requirements of the protocol. 13. Subject is able to voluntarily provide written informed consent.
Exclusion criteria
1. Has a disease that is suitable for therapy administered with curative intent. 2. Has any active, acute, or chronic infection(s) that are uncontrolled and/or requiring treatment, such as antibiotics 3. An active autoimmune disease that has required systemic treatment in the 2 years preceding the study 4. History of or plan for splenectomy or splenic irradiation 5. History of organ transplant or currently taking active immunosuppressive therapy 6. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) 7. Has known active or chronic Hepatitis B or Hepatitis C 8. History or evidence of cancer associated with immunodeficiency states 9. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 10. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment 11. Is expected to require any other form of antineoplastic therapy while on study 12. Had received live vaccines within 30 days prior to the first dose of trial treatment. 13. Has positive Immunoglobulin E (IgE) anti -Gal 14. Subject has a known allergy to alpha-Gal, such as red meat allergy, exposure to lone star tick (Amblyomma americanum), Ixodes ricinus/ holocyclus, or Cetuximab allergy 15. Has known allergy or hypersensitivity to any of the test compounds, materials or contraindication to test product 16. History or evidence of central nervous system metastases and/or carcinomatous meningitis (unless stable without treatment for at least 6 weeks and not requiring steroids) 17. Has received other experimental therapies or used an investigational device within 28 days of the first dose of treatment 18. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 14 days prior to study Day 1 or has not recovered from Adverse Event (AE) ≤ Grade 1 by treatment administered more than 14 days before first dose 19. Has had a prior anti-cancer monoclonal antibody (mAb) within 28 days prior to study Day 1 or who has not recovered from AE ≤ Grade 1 by treatment administered more than 28 days earlier. 20. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment. 21. Has unstable angina, new onset angina within the last 3 months, myocardial infarction within the last 6 months, uncontrolled atrial fibrillation, or current congestive heart failure with New York Heart Association Class III or higher. 22. Has a known current additional malignancy that is progressing or requires active treatment 23. O2 saturation \< 92% (on room air). 24. Has an underlying medical condition that would preclude study participation or other psychological, social or physical examination finding or a laboratory abnormality that the Investigator considers would make the subject a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results. 25. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of AGI-134 Injected Intra-tumourally (IT) | Up to 3 weeks after first administration of each dose level | Safety and tolerability of AGI-134 injected intra-tumourally (IT) by assessment of the percentage of participants who experienced a dose-limiting toxicity (DLT) . DLTs will be assessed during the first cycle (21 days) |
| Discontinue Study Drug Due to an Adverse Events | Approximately 12 months | Percentage of Participants Who Discontinue Study Drug Due to an Adverse Event (AE) AEs are defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study treatment, is also an AE. The percentage of participants who discontinue study treatment due to an AE will be presented |
Countries
Israel, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AGI-134 25mg/1mL AGI-134 1mL via IT injection. The proposed treatment is one dose of AGI-134 monotherapy per cycle; each cycle consists in three weeks, dosing will be given for 4 cycles. | 6 |
| AGI-134 50mg/2mL AGI-134 2mL via IT injection. The proposed treatment is one dose of AGI-134 monotherapy per cycle; each cycle consists in three weeks, dosing will be given for 4 cycles. | 19 |
| AGI-134 100mg/4mL AGI-134 4mL via IT injection. The proposed treatment is one dose of AGI-134 monotherapy per cycle; each cycle consists in three weeks, dosing will be given for 4 cycles. | 7 |
| AGI-134 200mg/8mL AGI-134 8mL via IT injection. The proposed treatment is one dose of AGI-134 monotherapy per cycle; each cycle consists in three weeks, dosing will be given for 4 cycles. | 6 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 |
| Overall Study | Clinical disease progression | 0 | 0 | 1 | 0 |
| Overall Study | Disease progression | 6 | 13 | 5 | 6 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 4 | 1 | 0 |
Baseline characteristics
| Characteristic | AGI-134 25mg/1mL | AGI-134 50mg/2mL | AGI-134 100mg/4mL | AGI-134 200mg/8mL | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 8 Participants | 2 Participants | 3 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 11 Participants | 5 Participants | 3 Participants | 20 Participants |
| Age, Continuous | 67.8 years STANDARD_DEVIATION 8.2 | 59.95 years STANDARD_DEVIATION 13.4 | 54 years STANDARD_DEVIATION 11 | 59.2 years STANDARD_DEVIATION 18.5 | 60 years STANDARD_DEVIATION 13.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 19 Participants | 6 Participants | 5 Participants | 36 Participants |
| Region of Enrollment Israel | 2 participants | 3 participants | 0 participants | 0 participants | 5 participants |
| Region of Enrollment Spain | 2 participants | 4 participants | 1 participants | 2 participants | 9 participants |
| Region of Enrollment United Kingdom | 2 participants | 12 participants | 6 participants | 4 participants | 24 participants |
| Sex: Female, Male Female | 1 Participants | 11 Participants | 2 Participants | 3 Participants | 17 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 5 Participants | 3 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 38 | 0 / 6 | 0 / 19 | 0 / 7 | 1 / 6 |
| other Total, other adverse events | 38 / 38 | 6 / 6 | 19 / 19 | 7 / 7 | 6 / 6 |
| serious Total, serious adverse events | 18 / 38 | 3 / 6 | 8 / 19 | 2 / 7 | 5 / 6 |
Outcome results
Primary
Discontinue Study Drug Due to an Adverse Events
Percentage of Participants Who Discontinue Study Drug Due to an Adverse Event (AE) AEs are defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study treatment, is also an AE. The percentage of participants who discontinue study treatment due to an AE will be presented
Time frame: Approximately 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AGI-134 25 mg | Discontinue Study Drug Due to an Adverse Events | 0 Participants |
| AGI-134 50 mg | Discontinue Study Drug Due to an Adverse Events | 1 Participants |
| AGI-134 100 mg | Discontinue Study Drug Due to an Adverse Events | 0 Participants |
| AGI-134 200 mg | Discontinue Study Drug Due to an Adverse Events | 0 Participants |
Primary
Safety and Tolerability of AGI-134 Injected Intra-tumourally (IT)
Safety and tolerability of AGI-134 injected intra-tumourally (IT) by assessment of the percentage of participants who experienced a dose-limiting toxicity (DLT) . DLTs will be assessed during the first cycle (21 days)
Time frame: Up to 3 weeks after first administration of each dose level
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AGI-134 25 mg | Safety and Tolerability of AGI-134 Injected Intra-tumourally (IT) | 0 Participants |
| AGI-134 50 mg | Safety and Tolerability of AGI-134 Injected Intra-tumourally (IT) | 0 Participants |
| AGI-134 100 mg | Safety and Tolerability of AGI-134 Injected Intra-tumourally (IT) | 0 Participants |
| AGI-134 200 mg | Safety and Tolerability of AGI-134 Injected Intra-tumourally (IT) | 0 Participants |