Trial Title:
TAC T-cells for the Treatment of Claudin 18.2 Positive Solid Tumors (TACTIC-3)
NCT ID:
NCT05862324
Condition:
Metastatic Solid Tumor
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
Claudin 18.2, Claudin+, Claudin Positive
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
In Phase 1, escalating doses of TAC01-CLDN18.2 will be evaluated to identify the RP2D
using the classic 3+3 dose escalation study design. In Phase 2, dose expansion groups
will further evaluate the safety, efficacy, and PK of the MTD or RP2D for TAC01-CLDN18.2
in subjects with gastric and esophageal AC (Group A), PDAC (Group B), and ovarian and
NSCLC cancers (Group C). In Phase 2, definitions of eligible CLDN18.2+ IHC expression
levels will be based on retrospective analysis of data from Phase 1 in association with
clinical efficacy because there are no formal CAP/ASCO definitions for CLDN18.2+ IHC
expression levels. In Phase 2, a Simon 2-stage design will be used to enroll up to 57
subjects in Group A and 22 subjects in Group C. Group B will enroll up to 10 subjects
without a Simon 2-stage design due to its historically low ORRs. The 10 treated subjects
in Group B are designed to seek evidence of potential efficacy in this difficult to treat
CLDN18.2+ subpopulation of PDAC.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
TAC01-CLDN18.2
Description:
TAC01-CLDN18.2 preceded by lymphodepletion with fludarabine or clofarabine,
cyclophosphamide, and nab-paclitaxel.
Arm group label:
TAC01-CLDN18.2
Summary:
TAC01-CLDN18.2 is a novel cell therapy that consists of genetically engineered autologous
T cells expressing T-cell Antigen Coupler (TAC) that recognizes Claudin 18.2. TAC directs
T-cells to the targeted antigen (CLDN 18.2), and once engaged with the target, activates
them via the endogenous T cell receptor.
This is an open-label, multicenter Phase ½ study that aims to establish safety, maximum
tolerated dose (MTD) or recommended Phase 2 dose (RP2D), pharmacokinetic profile and
efficacy of TAC01-CLDN18.2.
Detailed description:
The TAC technology is a novel approach to modifying T cells, herein referred to as TAC T
cells, and using them in the treatment of solid tumors. TAC T cells are produced through
genetic engineering, incorporating TAC receptors into a patient's own T cells. This
redirects these enhanced T cells to specific cancer antigens, and upon recognition,
activates them through the natural signaling pathways of the endogenous TCR.
In the TAC01-CLDN18.2 engineered T cell product; TAC T cells recognize the CLDN18.2, a
tight junction protein present on the surface of tumor cells, where the protein
expression is no longer limited to tight junctions and are visible to T cells to
eradicate them. Consequently, it is hypothesized TAC01-CLDN18.2 will be potentially safe
and active in treating patients with CLDN18.2+ solid tumors and provide a clinically
meaningful therapeutic benefit in patient populations with high unmet medical need.
This is a first-in-human study investigating TAC01-CLDN18.2 to evaluate the safety, MTD
or RP2D, PK, and efficacy in subjects with CLDN18.2+ solid tumors who have been treated
with at least 2 lines of prior therapy in Phase 1 and after at least 2 lines and no more
than 4 lines of prior therapy in Phase 2 (Note: in each phase, subjects with PDAC may
have been treated with 1 line of prior antineoplastic therapy. In addition, subjects who
are being treated with current lines of therapy, but not deriving benefit or not
tolerating therapy, and have not progressed maybe also eligible as long as they have
measurable disease at baseline as a starting reference point). In Phase 1, escalating
doses of TAC01-CLDN18.2 will be evaluated to identify the RP2D using the classic 3+3 dose
escalation study design.
In Phase 2, dose expansion groups will further evaluate the efficacy, safety, and PK of
the MTD or RP2D for TAC01-CLDN18.2 in subjects with gastric and esophageal AC (Group A),
PDAC (Group B), and mucinous ovarian and NSCLC cancers (Group C). In Phase 2, definitions
of eligible CLDN18.2+ IHC expression levels will be based on analysis of data from Phase
1 for signals of clinical activity since there are no formal CAP/ASCO guidelines for
CLDN18.2+ expression levels. In Phase 2, a Simon 2-stage design will be used to enroll up
to 57 subjects in Group A and 22 subjects in Group C. Group B (PDAC) will enroll up to 10
subjects as an exploratory cohort due to the historically low ORRs observed in PDAC. The
10 treated subjects in Group B are designed to seek evidence of potential clinical
activity in this difficult to treat CLDN18.2+ subpopulation of PDAC.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed, written informed consent obtained before any study procedures are conducted.
2. Age ≥ 18 years at the time of informed consent.
3. Tumor tissue samples positive for CLDN18.2 as assessed by central laboratory.
4. Histologically confirmed advanced, metastatic, unresectable CLDN18.2+ solid tumors
after at least 2 lines of prior therapy (Phase 1) and after at least 2 and no more
than 4 prior lines of therapy (Phase 2). Subjects with PDAC may have been treated
with 1 line of prior therapy.
1. Subjects with incurable Claudin 18.2 expressing malignancies for which no
standard-of-care targeted therapy exists may be enrolled regardless of the
number of prior treatment lines.
2. Specific Phase 1 tumor types include gastric, GEJ, esophageal adenocarcinoma,
PDAC, colorectal cancer, cholangiocarcinoma, ovarian mucinous cancer,
gallbladder cancer and NSCLC.
3. Specific Phase 2 tumor types include gastric and esophageal adenocarcinoma
(Group A), PDAC (Group B), and ovarian or NSCLC (Group C). Other tumor types
are not eligible.
5. Subjects with solid tumors with genetic alterations and mutations (e.g., BRAF, BRCA,
EGFR mutations, and ALK translocation) where approved targeted therapies were
available to their specific cancers must have been previously treated with such
approved therapies, or refused such approved targeted therapy for their cancers,
prior to enrollment, or in the opinion of the Investigator would be unlikely to
tolerate or derive clinically meaningful benefit from these standard-of-care
therapies.
6. Measurable disease per RECIST 1.1 at time of enrollment.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at Screening.
8. Life expectancy of at least 12 weeks.
9. Adequate organ and bone marrow reserve function prior to leukapheresis as outlined
in protocol.
10. Recovery to Grade ≤ 1 or baseline for any toxicities due to previous therapy, except
alopecia, anemia, thrombocytopenia, neutropenia, and neuropathy.
1. If a subject received major surgery, they must have recovered from the
procedure and/or any complications from the procedure prior to starting
TAC01-CLDN18.2 therapy.
2. Toxicity that has not recovered to Grade ≤ 1 is allowed if it meets the
inclusion requirements for laboratory parameters.
11. Adequate vascular access for leukapheresis as per institutional standards
12. For women physiologically capable of becoming pregnant, agreement to use highly
effective methods of contraception starting 28 days prior to study treatment and
continue for 1 year after the last TAC01-CLDN18.2 infusion. For men who have
partners physiologically capable of becoming pregnant, agreement to use an effective
barrier contraceptive method and refrain from donating sperm during study treatment
and for 1 year after the last TAC01-CLDN18.2 infusion.
13. Subjects who are hepatitis B surface antigen (HBsAg) positive are eligible if they
have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and
have undetectable HBV viral load prior to enrollment. Note: Subjects should remain
on antiviral therapy throughout study intervention and follow local guidelines for
HBV antiviral therapy post completion of study intervention.
14. Subjects with history of hepatitis C virus (HCV) infection are eligible if HCV viral
load is undetectable at Screening. Note: Subjects must have completed curative
antiviral therapy at least 4 weeks prior to enrollment.
Exclusion Criteria:
1. Intolerant to any component of TAC01-CLDN18.2
2. Prior treatment with any of the following:
1. Adoptive cell transfer of any kind, including CAR T cells.
2. Gene therapy
3. Prior treatment with a CLDN18.2 targeted agent (Phase 2 only)
4. Investigational medicinal product within 5 half-lives or 21 days prior to
leukapheresis, whichever is shorter.
5. Participation in or has participated in a study using an investigational device
within 4 weeks prior to the first dose of study treatment.
6. Receipt of a live or live-attenuated vaccine within 30 days prior to the first dose
of study Intervention. Administration of killed vaccines are allowed.
7. Radiation within 28 days prior to leukapheresis. Palliative radiation is allowed up
to 14 days prior to leukapheresis if additional non-irradiated lesions are present.
8. Chemotherapy or targeted small molecule therapy within 14 days prior to
leukapheresis, or within 7 days prior to leukapheresis for erlotinib, gefitinib,
afatinib, or crizotinib in NSCLC subjects.
9. Colony stimulating factors, including granulocyte-colony stimulating factor (G-CSF),
granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin, and other
hematopoietic cytokines, within 14 days prior to leukapheresis.
10. Immunosuppressive medication within 14 days or corticosteroid treatment < 72 hours
prior to leukapheresis, except for physiological replacement doses (< 12 mg/m2/24
hours of hydrocortisone or equivalent) and topical or inhaled steroids.
11. History or presence of clinically relevant central nervous system (CNS) pathology
such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injury, dementia,
Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
12. Known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study Screening),
clinically stable and without requirement of steroid treatment for at least 14 days
prior to first dose of study treatment.
13. Active inflammatory neurological disorders (e.g., Guillain-Barre Syndrome,
amyotrophic lateral sclerosis, multiple sclerosis).
14. Active autoimmune disease (e.g., lupus, rheumatoid arthritis, Sjogren's syndrome)
requiring systemic disease modifying agents in the past 2 years. Hormone replacement
therapy (e.g., thyroxine, insulin), or physiologic corticosteroid replacement
therapy (for adrenal or pituitary insufficiency, etc.) is not considered a form of
systemic treatment.
15. Active or uncontrolled hepatitis B or C (HCV ribonucleic acid [RNA] positive)
infection or any history of or active human immunodeficiency virus (HIV) infection.
16. Uncontrolled, acute, or life-threatening bacterial, viral, or fungal infection.
Subjects with ongoing use of prophylactic antibiotics, antifungals, or antivirals
are eligible if there is no evidence of active infection (includes COVID positive
subjects).
17. Class III or IV heart failure (as defined by the New York Heart Association [NYHA]),
cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other
clinically significant cardiac disease within 6 months prior to Screening.
18. Cardiac arrhythmia not controlled by medical management.
19. Clinically significant thrombotic events within 3 months prior to leukapheresis
and/or inability to stop anticoagulation for at least 2 weeks prior to
TAC01-CLDN18.2 infusion without compromising a subject's health (except in subjects
with PDAC).
20. Prior radiation therapy to the lung > 30 Gy within 6 months of the first dose of
study treatment.
21. History of Grade ≥ 3 drug-induced pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease.
22. Ongoing unstable or active gastrointestinal ulcers and gastrointestinal bleeding.
23. Complete gastric outlet syndrome or a partial gastric outlet syndrome with
persistent/recurrent vomiting.
24. History of organ transplantation or awaiting organ transplantation.
25. Known additional malignancy that is progressing or requires active treatment or has
been an incurable malignant tumor over the last 5 years. Exceptions include basal
cell carcinoma of the skin, non-metastatic squamous cell carcinoma of the skin, or
in situ cervical cancer that has undergone potentially curative therapy.
26. Pregnancy or lactation. Females physiologically capable of becoming pregnant must
have a negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test
result at Screening and within 48 hours prior to the first dose of LDC.
27. As determined by the Investigator, any uncontrolled medical, psychological,
familial, sociological, or geographical condition(s) that do(es) not permit
compliance with the protocol.
28. Has a known psychiatric or any disorder that would interfere with the participant's
ability to cooperate with the requirements of the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Southern California
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Status:
Recruiting
Contact:
Last name:
Xiomara Menendez
Email:
Xiomara.Menendez@med.usc.edu
Contact backup:
Last name:
Lorraine Martinez
Email:
Lorraine.Martinez@med.usc.edu
Investigator:
Last name:
Syma Iqbal, MD
Email:
Principal Investigator
Facility:
Name:
University of California San Diego
Address:
City:
San Diego
Zip:
92037
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gregory Botta, MD, PhD
Phone:
844-317-7836
Email:
alphastemcellclinic@health.ucsd.edu
Investigator:
Last name:
Gregory Botta, MD, PhD
Email:
Principal Investigator
Facility:
Name:
University of Miami Sylvester Comprehensive Cancer Center
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Stephanie Baboun
Email:
s.baboun1@miami.edu
Contact backup:
Last name:
Lauren Miro
Email:
lem183@med.miami.edu
Investigator:
Last name:
Peter Hosein, MD
Email:
Principal Investigator
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jordan Weiss
Email:
jordan_weiss@dfci.harvard.edu
Investigator:
Last name:
Benjamin Schlechter, MD
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sophie Hieronymi
Email:
hierons@mskcc.org
Investigator:
Last name:
Geoffrey Ku, MD
Email:
Principal Investigator
Facility:
Name:
Cincinnati Cancer Center
Address:
City:
Cincinnati
Zip:
45267
Country:
United States
Status:
Recruiting
Contact:
Last name:
Davendra Sohal, MD
Email:
cancer@uchealth.com
Investigator:
Last name:
Davendra Sohal, MD
Email:
Principal Investigator
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Miriam Gavriliuc
Email:
mngavriliuc@mdanderson.org
Investigator:
Last name:
Ecaterina Dumbrava, MD
Email:
Principal Investigator
Facility:
Name:
Princess Margaret Cancer Center
Address:
City:
Toronto
Zip:
M5G 2C1
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Tumor Immunotherapy Program
Email:
TIP@uhn.ca
Investigator:
Last name:
Sam Saibil, MD
Email:
Principal Investigator
Facility:
Name:
Centre hospitalier de l'Université de Montréal
Address:
City:
Montréal
Zip:
H2X 0C1
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Simon Turcotte, MD
Phone:
514-890-8000
Phone ext:
30737
Email:
uit.eligibilite.chum@ssss.gouv.qc.ca
Investigator:
Last name:
Simon Turcotte, MD
Email:
Principal Investigator
Start date:
August 23, 2023
Completion date:
August 1, 2027
Lead sponsor:
Agency:
Triumvira Immunologics, Inc.
Agency class:
Industry
Source:
Triumvira Immunologics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05862324
