A Phase I Interventional Open-Label, Non-Randomized Dose-Escalation Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Preliminary Anti-Tumor Activity of Autologous p95HER2.CAR-TECH2Me T Cells in Patients with Selected Advanced Cancers. Catherine Trial
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase I
PATOLOGÍA
Leucemia linfática crónica y otros SLPC, Leucemia linfoblástica aguda, Leucemia mieloide aguda, Terapia celular y T-CARs, Trasplante de progenitores hematopoyéticos, Linfoma
FECHA DE APERTURA
Diciembre, 2025
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
6) Patients must have histologically or cytologically proven unresectable or metastatic tumors. The disease must be refractory to standard therapy or in the first line if they are unable to receive standard therapy or no standard therapy exists for a particular disease. a) Select tumor types: breast, gastric, and endometrial tumors. Other selected solid tumors may be included per investigator discretion
15) Patients who are of childbearing potential (postmenarcheal who has not reached a postmenopausal state and has not undergone surgical sterilization) or have partners of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 12 months after the infusion of the p95HER2.CAR-TECH2Me product.
1) Female participants: a female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a) Women of non-childbearing potential (WONCBP). b) Women of childbearing potential (WOCBP), who: i) Agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year from screening until 12 months after the infusion of the p95HER2.CAR-TECH2Me product. Have a negative pregnancy test (blood) within one week before the first study treatment administration
17) Male Participants: during the treatment period and for at least 6 months after the last dose of study treatment, agreement to: a) Remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom or a contraceptive method that result in a failure rate of <1% per year, with partners who are WOCBP. b) Refrain from donating sperm during the study. c) Inform if his partner gets pregnant during this time.
18) Adequate expanding p95HER2.CAR-TECH2Me cells as defined by the T cell production manual before preparative lymphodepleting chemotherapy infusion (available autologous transduced T lymphocytes with 15% or more expression of p95HER2.CAR-TECH2Me as determined by flow-cytometry and killing of p95HER2-positive targets 20 % or greater in cytotoxicity assay.)
19) Any toxicity related to prior systemic therapy must have recovered to grade 1 or less according to NCI-CTCAE v5.0 at least 4 weeks before treatment enrollment, except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy, and Grade 2 peripheral neuropathy. Note: Other Grade 2 AEs that are deemed clinically insignificant by treating physician and in consultation with Medical Monitor are permitted.
20) Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.
7) Positivity for HER-2 expression according to international society guidelines (score in a ISO-certied clinical or equivalent laboratory). To meet study entry eligibility, tumors are required to have at least an intensity score 3+ for HER2 staining following the manufacturers recommendations
Measurable disease by the RECIST v. 1.1 criteria
9) Patients are considered medically fit enough to undergo all study procedures and interventions and adequate hematological, renal, and hepatic functions
10) Patients must be seronegative for HIV antibody
Patients must be seronegative for active hepatitis B and seronegative for hepatitis C antibody.
12) Patients must have blood tests results negative for active tuberculosis, syphilis, herpes simplex virus, cytomegalovirus, HTLV or Epstein-Barr virus infection.
13) Patients with documented LVEF of 50%.
14) Patients with documented FEV1, FVC, and DLCO 50% tested by a pulmonary function test.
15) Patients who are of childbearing potential (postmenarcheal who has not reached a postmenopausal state and has not undergone surgical sterilization) or have partners of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 12 months after the infusion of the p95HER2.CAR-TECH2Me product.
1) Female participants: a female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a) Women of non-childbearing potential (WONCBP). b) Women of childbearing potential (WOCBP), who: i) Agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year from screening until 12 months after the infusion of the p95HER2.CAR-TECH2Me product. Have a negative pregnancy test (blood) within one week before the first study treatment administration
17) Male Participants: during the treatment period and for at least 6 months after the last dose of study treatment, agreement to: a) Remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom or a contraceptive method that result in a failure rate of <1% per year, with partners who are WOCBP. b) Refrain from donating sperm during the study. c) Inform if his partner gets pregnant during this time.
18) Adequate expanding p95HER2.CAR-TECH2Me cells as defined by the T cell production manual before preparative lymphodepleting chemotherapy infusion (available autologous transduced T lymphocytes with 15% or more expression of p95HER2.CAR-TECH2Me as determined by flow-cytometry and killing of p95HER2-positive targets 20 % or greater in cytotoxicity assay.)
19) Any toxicity related to prior systemic therapy must have recovered to grade 1 or less according to NCI-CTCAE v5.0 at least 4 weeks before treatment enrollment, except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy, and Grade 2 peripheral neuropathy. Note: Other Grade 2 AEs that are deemed clinically insignificant by treating physician and in consultation with Medical Monitor are permitted.
20) Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.
7) Positivity for HER-2 expression according to international society guidelines (score in a ISO-certied clinical or equivalent laboratory). To meet study entry eligibility, tumors are required to have at least an intensity score 3+ for HER2 staining following the manufacturers recommendations
Measurable disease by the RECIST v. 1.1 criteria
9) Patients are considered medically fit enough to undergo all study procedures and interventions and adequate hematological, renal, and hepatic functions
10) Patients must be seronegative for HIV antibody
Patients must be seronegative for active hepatitis B and seronegative for hepatitis C antibody.
12) Patients must have blood tests results negative for active tuberculosis, syphilis, herpes simplex virus, cytomegalovirus, HTLV or Epstein-Barr virus infection.
13) Patients with documented LVEF of 50%.
14) Patients with documented FEV1, FVC, and DLCO 50% tested by a pulmonary function test.
CRITERIOS DE EXCLUSIÓN
1) Patients with symptomatic and/or untreated brain metastases.
10) Patients with current or history within the last 6 months, as determined by the Investigator, of clinically significant, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease.
11) Patients with a history of coronary revascularization or ischemic symptoms.
12) History of idiopathic pulmonary fibrosis or evidence of active pneumonitis (any origin)
13) Patients with allergies to any of the compounds included in any of the treatment products.
14) Patients with contraindications for cyclophosphamide and fludarabine at per protocol doses (see Investigator Brochure for details).
15) Patients who have received any approved anti-cancer cytotoxic, anti-angiogenic and ICB therapy including radiotherapy within 4 weeks before preparative lymphodepleting therapy.
16) Patients who have received any non-cytotoxic drug and molecular targeted therapy within 4 weeks before preparative lymphodepleting therapy (or within five half-lives of the investigational product, whichever is shorter).
17) Patients who have received any investigational agent within 4 weeks before preparative lymphodepleting therapy (or within five half-lives of the investigational product, whichever is shorter).
18) Patients who have received a live, attenuated vaccination within the 4 weeks before lymphodepleting therapy.
19) Patients who have undergone major surgery in the previous 3 weeks before lymphodepleting therapy.
2) Patients with leptomeningeal carcinomatosis.
20) Patients who have previously received any investigational cell or gene therapies.
21) Women of childbearing potential who are pregnant or breastfeeding.
22) Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
23) Other severe, acute, or chronic medical condition or laboratory abnormality that may increase the risk associated with study assessed by the Investigator.
3) Patients with an active concurrent or history within the past 3 years of invasive malignancy, except for non-melanoma skin cancer, cervical and bladder carcinoma in situ, good prognosis ductal carcinoma in situ of the breast, or prostate carcinoma that is in remission under androgen deprivation therapy for > 2 years. Other exceptions may apply and require discussion between the Investigator and the Medical Monitor.
4) Patients with an active systemic infection requiring anti-infective treatment within 14 days before preparative lymphodepleting therapy.
5) Patients with active hepatitis B or hepatitis C.
6) Patients with active autoimmune disease requiring immunosuppressive treatments.
7) Patients with a history of organ or bone marrow transplantation.
8) Patients with any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
9) Patients requiring regular treatment with steroids.
10) Patients with current or history within the last 6 months, as determined by the Investigator, of clinically significant, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease.
11) Patients with a history of coronary revascularization or ischemic symptoms.
12) History of idiopathic pulmonary fibrosis or evidence of active pneumonitis (any origin)
13) Patients with allergies to any of the compounds included in any of the treatment products.
14) Patients with contraindications for cyclophosphamide and fludarabine at per protocol doses (see Investigator Brochure for details).
15) Patients who have received any approved anti-cancer cytotoxic, anti-angiogenic and ICB therapy including radiotherapy within 4 weeks before preparative lymphodepleting therapy.
16) Patients who have received any non-cytotoxic drug and molecular targeted therapy within 4 weeks before preparative lymphodepleting therapy (or within five half-lives of the investigational product, whichever is shorter).
17) Patients who have received any investigational agent within 4 weeks before preparative lymphodepleting therapy (or within five half-lives of the investigational product, whichever is shorter).
18) Patients who have received a live, attenuated vaccination within the 4 weeks before lymphodepleting therapy.
19) Patients who have undergone major surgery in the previous 3 weeks before lymphodepleting therapy.
2) Patients with leptomeningeal carcinomatosis.
20) Patients who have previously received any investigational cell or gene therapies.
21) Women of childbearing potential who are pregnant or breastfeeding.
22) Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
23) Other severe, acute, or chronic medical condition or laboratory abnormality that may increase the risk associated with study assessed by the Investigator.
3) Patients with an active concurrent or history within the past 3 years of invasive malignancy, except for non-melanoma skin cancer, cervical and bladder carcinoma in situ, good prognosis ductal carcinoma in situ of the breast, or prostate carcinoma that is in remission under androgen deprivation therapy for > 2 years. Other exceptions may apply and require discussion between the Investigator and the Medical Monitor.
4) Patients with an active systemic infection requiring anti-infective treatment within 14 days before preparative lymphodepleting therapy.
5) Patients with active hepatitis B or hepatitis C.
6) Patients with active autoimmune disease requiring immunosuppressive treatments.
7) Patients with a history of organ or bone marrow transplantation.
8) Patients with any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
9) Patients requiring regular treatment with steroids.
DESCRIPCIÓN
To evaluate the safety and tolerability of the administration of p95HER2.CAR-TECH2Me cells in our target patients and to identify the maximum tolerated dose (MTD) and recommended phase-2 dose (RP2D).
PALABRAS CLAVE
acute lymphoblastic leukemia, acute myeloid leukemia, autologous, car-t, car-t dual, dual car-t, leucemia linfocítica crónica (llc / cll), ph + acute lymphoblastic leukemia, philadelphia positive acute lymphoblastic leukemia
