HumRes53236
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SNCTP000004153
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BASEC2020-01969
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NCT04046445
A phase Ib study evaluating ATP128, VSV-GP128, and BI 754091 in patients with stage IV colorectal cancer (KISIMA-01)
Résumé de l'étude
This phase Ib study aims to evaluate the safety and tolerability as well as the efficacy of a therapeutic vaccine called ATP128 administered alone (Cohort 1a) or in combination with an antibody called BI 754091 (double combination in Cohorts 2a, 2b, and 2c) or in combination with an antibody called BI 754091 and an oncolytic viral vaccine called VSV-GP128 (triple combination in Cohorts 3, 4a, and 4b) in patients with stage IV colorectal cancer. It is planned to include 96 patients distributed across 8 cohorts (1a, 1b, 2a, 2b, 2c, 3, 4a, 4b) according to the specifics of their disease. Cohorts 1a, 1b, and 2a are now closed to recruitment. Nine patients refractory to prior treatments have been included in Cohort 1a. In total, eleven patients who responded to first-line chemotherapy have been included in Cohorts 1b and 2a and received ATP128 in combination with BI 754091. The same patient population will be included in Cohorts 2c, 3, and 4a and will receive the triple combination (ATP128, VSV-GP128, and BI 754091). Six patients with liver-limited disease and operable hepatic metastases (resection) have been included in Cohort 2b and received ATP128 in combination with BI 754091. Cohort 2b is still open for recruitment. The same patient population will be included in Cohort 4b and will receive the triple combination (ATP128, VSV-GP128, and BI 754091).
(BASEC)
Intervention étudiée
Administration of a therapeutic vaccine ATP128 alone or in combination with an antibody BI 754091 (PD-1 inhibitor) or in combination with an antibody called BI 754091 and an oncolytic viral vaccine called VSV-GP128. Cohort 2c: patients will receive 6 subcutaneous injections of ATP128 and at least 7 infusions of BI 754091 over a duration of 4.5 months, which may extend to 12 months of treatment with BI 754091 in case of treatment benefit. Cohorts 3, 4a: patients will receive 5 subcutaneous injections of ATP128, one intravenous injection of VSV-GP128, and at least 7 infusions of BI 754091 over a duration of 4.5 months, which may extend to 12 months of treatment with BI 754091 in case of treatment benefit. Cohort 2b: patients will receive 6 subcutaneous injections of ATP128 and 7 infusions of BI 754091, before and after their surgery, over a duration of 4.5 months. Cohort 4b: patients will receive 5 subcutaneous injections of ATP128, one intravenous injection of VSV-GP128, and 7 infusions of BI 754091, before and after their surgery, over a duration of 4.5 months.
(BASEC)
Maladie en cours d'investigation
Stage IV colorectal cancer
(BASEC)
Critères de participation
Cohorts 2c, 3, and 4a (Cohorts 1b, 2a closed): - Microsatellite Stable (MSS) / Microsatellite Mismatch Repair proficient (MMRp) CRC confirmed by PCR / immunohistochemistry or NGS performed within the institution. - Must have received and completed a first line of systemic SoC therapy (physician's choice) for the treatment of stage IV disease. Must have a partial response (PR) or stable disease (SD) ongoing at the end of this treatment, the end being defined by the investigator, however with a minimum of 4 months of treatment. - Presence of at least one liver lesion suitable for two biopsies, ideally not the one used for measurement. Cohort 2b, 4b: - No disease progression after neoadjuvant chemotherapy. - MSS/MMRp CRC confirmed by PCR / immunohistochemistry or NGS performed within the institution. - Radiological evidence of stage IV CRC limited to the liver. - Eligible for complete R0 hepatic metastasectomy (in case the primary tumor has already been removed) or for complete simultaneous combined R0 resection (resection of both hepatic metastases and primary tumor in case the primary tumor is still in place) with curative intent. - Must have received neoadjuvant systemic SoC therapy (physician's choice) for stage IV disease. May have received up to 16 weeks of this systemic treatment. Cohorts 3, 4a, 4b: - The patient agrees to follow the instructions and precautions related to the potential excretion of VSV-GP128. (BASEC)
Critères d'exclusion
All cohorts: - Prior therapy with checkpoint inhibitors within 4 weeks or 5 half-lives (whichever is shorter) before administration of the study treatment, except for bevacizumab (Avastin®) which may have been received within 15 days prior to the initiation of the study treatment. - Prior chemotherapy or targeted molecule therapy received within 15 days prior to the initiation of the study treatment. - Prior radiotherapy received within 2 weeks prior to enrollment or within 4 weeks prior to enrollment in the case of central nervous system irradiation that requires a wash-out period of ≥ 4 weeks. Patients must have recovered from all radiation-related toxicities without having resorted to corticosteroids, and without radiation pneumonitis. Cohorts 1b, 2a, 2b, 2c, 3, 4a, 4b: - Have received more than one line of treatment for stage IV disease (neoadjuvant treatment in Cohort 2b and 4b counts as 1 line). - History of pneumonitis in the last 5 years. Cohorts 3, 4a, 4b: - Use of tamoxifen in the month prior to the start of the study treatment. - Prior treatment with VSV. (BASEC)
Cohorts 2c, 3, and 4a (Cohorts 1b, 2a closed): - Microsatellite Stable (MSS) / Microsatellite Mismatch Repair proficient (MMRp) CRC confirmed by PCR / immunohistochemistry or NGS performed within the institution. - Must have received and completed a first line of systemic SoC therapy (physician's choice) for the treatment of stage IV disease. Must have a partial response (PR) or stable disease (SD) ongoing at the end of this treatment, the end being defined by the investigator, however with a minimum of 4 months of treatment. - Presence of at least one liver lesion suitable for two biopsies, ideally not the one used for measurement. Cohort 2b, 4b: - No disease progression after neoadjuvant chemotherapy. - MSS/MMRp CRC confirmed by PCR / immunohistochemistry or NGS performed within the institution. - Radiological evidence of stage IV CRC limited to the liver. - Eligible for complete R0 hepatic metastasectomy (in case the primary tumor has already been removed) or for complete simultaneous combined R0 resection (resection of both hepatic metastases and primary tumor in case the primary tumor is still in place) with curative intent. - Must have received neoadjuvant systemic SoC therapy (physician's choice) for stage IV disease. May have received up to 16 weeks of this systemic treatment. Cohorts 3, 4a, 4b: - The patient agrees to follow the instructions and precautions related to the potential excretion of VSV-GP128. (BASEC)
Critères d'exclusion
All cohorts: - Prior therapy with checkpoint inhibitors within 4 weeks or 5 half-lives (whichever is shorter) before administration of the study treatment, except for bevacizumab (Avastin®) which may have been received within 15 days prior to the initiation of the study treatment. - Prior chemotherapy or targeted molecule therapy received within 15 days prior to the initiation of the study treatment. - Prior radiotherapy received within 2 weeks prior to enrollment or within 4 weeks prior to enrollment in the case of central nervous system irradiation that requires a wash-out period of ≥ 4 weeks. Patients must have recovered from all radiation-related toxicities without having resorted to corticosteroids, and without radiation pneumonitis. Cohorts 1b, 2a, 2b, 2c, 3, 4a, 4b: - Have received more than one line of treatment for stage IV disease (neoadjuvant treatment in Cohort 2b and 4b counts as 1 line). - History of pneumonitis in the last 5 years. Cohorts 3, 4a, 4b: - Use of tamoxifen in the month prior to the start of the study treatment. - Prior treatment with VSV. (BASEC)
Lieu de l’étude
Genève, Zurich
(BASEC)
Belgium, Germany, Switzerland, United States (ICTRP)
Sponsor
AMAL Therapeutics S.A.
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Delphine Gani
022 594 39 39 / 63
delphine.gani@clutterboehringer-ingelheim.comAMAL Therapeutics S.A.
(BASEC)
Informations générales
MD Anderson
(ICTRP)
Informations scientifiques
MD Anderson
(ICTRP)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale d'éthique de Genève
(BASEC)
Date d'approbation du comité d'éthique
23.11.2020
(BASEC)
Identifiant de l'essai ICTRP
NCT04046445 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
KISIMA-01: An Open-Label, Multicenter, Non-Randomized, Dose- Confirmation and Cohort-Expansion Phase 1b Study to Evaluate the Safety, Tolerability, and Anti-Tumor Activity of ATP128, VSV-GP128 and BI 754091, in Patients with Stage IV Colorectal Cancer (BASEC)
Titre académique
An Open-Label, Multicenter, Non-Randomized, Dose-Confirmation and Cohort-Expansion Phase 1b Study to Evaluate the Safety, Tolerability, and Anti-Tumor Activity of ATP128, VSV-GP128 and BI 754091, in Patients With Stage IV Colorectal Cancer (ICTRP)
Titre public
Phase 1b Study to Evaluate ATP128, VSV-GP128 and BI 754091, in Patients With Stage IV Colorectal Cancer (ICTRP)
Maladie en cours d'investigation
Colorectal Cancer;MSS;Stage IV Colon Cancer;Stage IV Rectal Cancer;Metastatic Colorectal Cancer;Liver Metastasis Colon Cancer (ICTRP)
Intervention étudiée
Drug: ATP128;Drug: BI 754091;Drug: VSV-GP128 (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Critères d'inclusion/exclusion
Gender: All
Maximum age: N/A
Minimum age: 18 Years
Inclusion Criteria:
Cohort 1a
1. Ability to comprehend and willingness to provide written informed consent (ICF) for
the study.
2. Age = 18 years.
3. Patient with histologically or cytologically confirmed stage IV CRC who has failed
standard therapies.
4. Must have received Standard of Care systemic treatment consisting of
fluoropyrimidin- oxaliplatin and/or irinotecan based therapy for stage IV CRC
disease.
5. Presence of at least 1 measurable lesion by computed tomography or magnetic
resonance imaging per RECIST v1.1 as determined by the local site
investigator/radiologist assessment.
6. Presence of at least one liver lesion amenable to repeated biopsy, ideally not the
one being used for measuring.
7. Willingness to undergo two fresh liver biopsies (pre-treatment and on-treatment).
8. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
9. Life expectancy of at least 3 months.
10. Resolution of all toxicities and any toxic effect(s) of the most recent prior
therapy to Grade 1 or less (except alopecia). Patients with = Grade 2 neuropathy and
Grade = 2 fatigue are an exception and may enroll.
11. Adequate renal, hepatic, and hematologic functions as defined by laboratory
parameters = 7 days before study treatment initiation.
12. Absolute neutrophil count (ANC) = 1.5 ? 109/L.
13. Absolute lymphocyte count = 0.5 ? 109/L.
14. Platelets = 100 ? 109/L.
15. Hemoglobin level = 9 g/dL.
16. Measured or calculated creatinine clearance (glomerular filtration rate can also be
used in place of creatinine clearance) = 50 mL/min according to the formula of
Cockcroft-Gault.
17. Total bilirubin = 1.5 ? upper limit of normal (ULN); if total bilirubin is > 1.5 x
ULN then direct bilirubin must be = 1.5 ? ULN. Patients with known Gilbert's
Syndrome may enroll if total bilirubin = 3 ? ULN.
18. Alanine aminotransferase/aspartate aminotransferase (ALT/AST) = 2.5 ? ULN or = 5 x
ULN in patients with hepatic involvement.
19. A female patient is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to use highly
effective contraceptive methods during the treatment period and for at least 180
days after the last dose of study treatment and refrain from egg donation during
this period.
20. A male patient must agree to use a contraceptive during the treatment period and for
at least 180 days after the last dose of study treatment and refrain from donating
sperm during this period.
Cohorts 1b, 2a, 2c, 3 and 4a:
1. Ability to comprehend and willingness to provide written informed consent (ICF) for
the study.
2. Age = 18 years.
3. Histologically or cytologically confirmed CRC and MSS/MMR proficient status
confirmed by polymerase chain reaction (PCR)/ immunohistochemistry or next
generation sequencing (NGS) assay at local institution.
4. Must have received a first line of SoC systemic therapy (physician choice) for stage
IV disease and completed the therapy. They must have an ongoing partial response
(PR) or a stable disease (SD) at the completion of this therapy, completion of
therapy as defined by the investigator, however, with a minimum number of 4 months.
Note: Patient may have also received prior adjuvant therapy for stage II or III
colorectal cancer, however the adjuvant treatment for stage II and III will not be
considered as a prior line of therapy in case of relapse more than 6 months after
the end of treatment.
5. Presence of at least 1 measurable lesion by computed tomography or magnetic
resonance imaging per RECIST v1.1 as determined by the local site
investigator/radiologist assessment.
6. Presence of at least one metastatic lesion amenable to paired biopsies (same lesion
to be biopsied twice, at baseline and on D36), ideally not the one being used for
measuring. However, liver lesions must be prioritized. Non-liver metastatic lesion
biopsies may be collected only if the patient has no liver lesion or if the liver
lesion is not amenable to paired biopsies (e.g. due to its size or location) or if
the liver biopsy represents a risk or an undue inconvenience for the patient
health/condition per Investigator judgment. In such cases, where a patient has no
lesion amenable to biopsy at all, the paired biopsies may be waived by the Sponsor
on a case-by-case basis.
7. Willingness to undergo two biopsies (liver lesion must be prioritized). If the
Investigator judges the biopsies to be a risk or an undue inconvenience for the
patient health/condition, they may be waived by the Sponsor on a case-by-case basis.
8. ECOG performance status 0 to 2.
9. Life expectancy of at least 6 months.
10. Has resolution of all toxicities and any toxic effect(s) of the most recent prior
therapy to Grade 1 or less (except alopecia). Patients with = Grade 2 neuropathy and
Grade = 2 fatigue are an exception and may enroll.
11. Adequate renal, hepatic, thyroid and hematologic functions as defined by laboratory
parameters = 7 days before study treatment initiation.
12. Absolute neutrophil count = 1.5 ? 109/L.
13. Absolute lymphocyte count = 0.5 ? 109/L.
14. Platelets = 100 ? 109/L.
15. Hemoglobin level = 9 g/dL.
16. Measured or calculated creatinine clearance (glomerular filtration rate can also be
used in place of creatinine clearance) = 50 mL/min according to the formula of
Cockcroft-Gault (see Appendix 6).
17. Total bilirubin = 1.5 ? ULN; if total bilirubin is > 1.5 x ULN then direct bilirubin
must be = 1.5 ? ULN. Patients with known Gilbert's Syndrome may enroll if total
bilirubin = 3 ? ULN.
18. ALT/AST = 2.5 ? ULN or = 5 ? ULN in patients with hepatic involvement.
19. A female patient is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to use highly
effective contraceptive methods during the treatment period and for at least 180
days after the last dose of study treatment and refrain from egg donation during
this period.
20. A male patient must agree to use a contraceptive during the treatment period and for
at least 180 days after the last dose of study treatment and refrain from donating
sperm during this period.
Specific to Cohorts 3, 4a, 4b:
1. Patient agrees to follow the instructions and precautions (see Section 4.4.1)
related to potential VSV-GP128 shedding.
Cohorts 2b and 4b:
1. Ability to comprehend and willingness to provide written informed consent (ICF) for
the study.
2. Age = 18 years.
3. Histologically or cytologically confirmed CRC and MSS/MMR proficient status
confirmed by PCR/immunohistochemistry or NGS assay at local institution.
4. Radiological evidence (CT/MRI) of liver-limited stage IV CRC.
5. Must have received first line neoadjuvant SoC systemic therapy (physician choice)
for stage IV disease. May have received up to (ICTRP)
non disponible
Critères d'évaluation principaux et secondaires
Evaluate safety and tolerability by measure of incidence of treatment-emergent adverse events (AEs) and serious adverse events (SAEs) graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0;valuate anti-tumor effect of study treatment by measure of Progression-free survival (PFS) (ICTRP)
Evaluate anti-tumor effect of study treatment by measure of Overall Response (OR);Confirm recommended phase 2 dose (RP2D) of study treatment;Further evaluate anti-tumor effect of study treatment of Best Overall Response (BOR);Evaluate anti-tumor effect of study treatment by measure of Duration of Response (DoR);Evaluate anti-tumor effect of study treatment by measure of Progression Free Survival (PFS);Evaluate anti-tumor effect of study treatment by measure of Relapse Free Survival (RFS) (ICTRP)
Date d'enregistrement
non disponible
Inclusion du premier participant
non disponible
Sponsors secondaires
Boehringer Ingelheim (ICTRP)
Contacts supplémentaires
Scott Kopetz, MD Anderson (ICTRP)
ID secondaires
2019-000728-16, 2021DR1011, KISIMA-01 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/ct2/show/NCT04046445 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
non disponible