Trial Title:
An Open Label Dose Finding Study of PTT-4256 in Patients With Solid Tumours.
NCT ID:
NCT06634849
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
PTT-4256, GPR65, oncology, cancer
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
PTT-4256
Description:
Single oral intake of PTT-4256 followed by treatment-free period of 3 days to assess
safety, PK and PD. After 72-hr post dose PK sample, first 21day cycle of once daily
PTT-4256 will begin to assess DLTs. Cohort 1-3 will receive 10mg, 20mg & 40mg.
Arm group label:
PTT-4256
Summary:
This open label, dose escalation module will evaluate the safety, tolerability, PK, PD,
and preliminary efficacy of PTT-4256 in participants with solid tumours using a
combination of accelerated dose titration (ADT) and Bayesian Optimal Interval (BOIN)
design.
Detailed description:
Module A- This module also aims to determine the MTD, if reached, and preliminary OBD
(optimal biological dose) and RP2D (Recommended Phase 2 dose). Eligible participants will
be adults with cytologically or histologically confirmed solid malignancy and locally
advanced or metastatic disease who require systemic treatment for their tumour and are
either refractory to, have progressed on, are intolerant to, or are not otherwise a
candidate, in the opinion of the Investigator, for any of the currently available
standard treatments.
Module A will employ an ADT design for the first 2 cohorts (Cohorts A1 and A2) followed
by a BOIN design for the subsequent cohorts (Cohorts A3 onwards). Participants will
undergo a Screening period beginning up to 28 days prior to first dose and will be
required to sign an informed consent form (ICF) before undertaking any study-specific
procedures or assessments.
Participants who meet all of the inclusion and none of the exclusion criteria will be
enrolled.
Safety oversight will be provided by a Safety Review Committee (SRC) comprising the
Investigators, the Sponsor's Medical Monitor (MM)/representatives and other independent
specialists (e.g. statistician).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. ≥ 18 years of age at the time of consent.
2. Participant has given written informed consent to participate in the study and is
able and willing to adhere to the study protocol.
3. Participant has cytologically or histologically confirmed solid malignancy and has
locally advanced or metastatic disease. Melanoma, non-small cell lung cancer, renal
cell carcinoma, metastatic castrate-resistant prostate cancer, cervix cancer, triple
negative breast cancer, colorectal cancer, gastric cancer are preferred solid
tumours.
4. Participant must require systemic treatment for their tumour and either:
1. be refractory to,
2. have progressed on,
3. be intolerant to, or
4. be not otherwise a candidate - in the opinion of the Investigator - for any of
the currently available standard treatments.
5. Participant has measurable disease per RECIST v1.1. Participants with non-measurable
disease per RECIST v1.1 might be considered eligible upon discussion with the
Sponsor.
6. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0
to 1.
7. Participant has an estimated life expectancy of at least 3 months in the opinion of
the Investigator.
8. Adequate haematological (blood or platelet transfusion not allowed within 7 days
prior to Screening), liver, and renal function defined below (repeat measurement of
borderline values permitted):
- Haemoglobin ≥ 8.5 g/dL,
- Absolute neutrophil count (ANC) ≥ 1.5 × 109/L,
- Platelet count ≥ 90 x 109/L,
- Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN), (or where ≤ 2
× ULN with known hepatobiliary metastases or Gilbert's syndrome),
- Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 2.5 × ULN (or ≤ 5
×ULN if liver metastases are present),
- Estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 (calculated
using Cockcroft-Gault).
9. Females:
1. must not be pregnant or lactating, and must use acceptable, highly effective
contraception from Screening until 90 days after last IMP administration.
Effective forms of contraception are defined in Section 7.3.2,
2. Females with same-sex partners (abstinence from penile-vaginal intercourse) or
who are abstinent from heterosexual intercourse are not required to use
contraception when this is their preferred and usual lifestyle,
3. Women of childbearing potential (WOCBP) must have a negative pregnancy test at
Screening and Day 1 and be willing to have additional pregnancy tests as
required throughout the study. WOCBP must not donate ova from signing informed
consent until at least 90 days after the last IMP administration.
4. Women of non-childbearing potential (WONCBP) must be postmenopausal for ≥12
months or ≥ 60 years of age at the time of consent (postmenopausal status is to
be confirmed through testing of follicle-stimulating hormone (FSH) levels ≥ 40
IU/L (except for participants on hormone replacement therapy) at Screening for
amenorrhoeic female participants).
10. Males:
1. must be surgically sterile (> 6 months since vasectomy with confirmation of no
viable sperm),
2. or if engaged in sexual relations (intercourse) with a WOCBP, either his
partner must be surgically sterile (eg, hysterectomy, bilateral salpingectomy,
bilateral oophorectomy), or an acceptable, highly effective contraceptive
method must be used from Screening until 90 days after last IMP administration,
3. Males with same-sex partners (abstinence from penile-vaginal intercourse) or
who are abstinent from heterosexual intercourse are not required to use
contraception when this is their preferred and usual lifestyle,
4. Males must not donate sperm from the first dose of IMP until at least 90 days
after the last dose of IMP
Exclusion Criteria:
1. Inability or unwillingness to adhere to the study protocol, including study
procedures and oral intake of the IP.
2. Active primary central nervous system (CNS) malignancy, active CNS metastases or
leptomeningeal disease. Participants with previously treated primary CNS malignancy
or CNS metastases are eligible to participate if:
1. they have stable and controlled neurological symptoms without deterioration;
2. they have stable disease as assessed by imaging (preferably contrast-enhanced
MRI) for at least 28 days prior to first IMP administration;
3. they have no evidence of new or enlarging brain metastases; and
4. they are not using corticosteroids for at least 7 days prior to first IMP
administration.
3. Unresolved or unstable serious toxic side effects of prior chemotherapy or
radiotherapy, ie, ≥ Grade 2 per CTCAE v5.0 except fatigue, alopecia, infertility, or
those relating to palliative radiotherapy within 6 weeks prior to first IMP
administration. Participants with residual AEs > Grade 1 considered not clinically
significant may be considered eligible on a case-by-case basis, in discussion with
the Sponsor.
4. Concurrent active or previous history of other malignancy within the past 2 years
before first IMP administration except:
1. Malignancy (other than in situ) treated with curative intent and with no known
active disease present for ≥ 2 years before first IMP administration and felt
to be at low risk of recurrence by the Investigator;
2. Adequately treated non-melanoma skin cancer or lentigo malignant with no
evidence of disease;
3. Adequately treated in situ cancer without evidence of disease.
5. Received anti-cancer therapy (including chemotherapy, immunotherapy, radiation
therapy, biologic therapy, or any investigational therapy) within 28 days or 5
half-lives of the therapeutic agent, whichever is shorter, prior to the first IMP
administration. Palliative adiotherapy given within 28 days prior to the first IMP
administration may be considered eligible on a case-by-case basis, in discussion
with the Sponsor.
6. Uncontrolled symptomatic malignant effusion(s) or those requiring recurrent drainage
in the opinion of the Investigator.
7. Participants with clinically significant active autoimmune or chronic inflammatory
disease that is not well controlled with standard therapy in the opinion of the
Investigator.
8. Grade 3 or higher immunotherapy-induced autoimmune hepatitis.
9. Participants with:
1. symptomatic colitis of any CTCAE v5.0 Grade and aetiology within 4 weeks before
first dosing,
2. a history of autoimmune (including but not restricted to Crohn's disease,
ulcerative colitis, and celiac's disease) or idiopathic (including but not
restricted to pseudomembranous, ischaemic and microscopic) colitis, and/or,
3. a history of drug-induced colitis of CTCAE v5.0 Grade 3 or higher.
10. History of primary immunodeficiency, bone marrow transplantation or solid organ
transplantation.
11. Use of systemic immunosuppressive medication (including > 10 mg prednisolone per day
or equivalent) within 14 days prior to the first IMP administration. Note that use
of immunosuppressive medications as prophylaxis in participants with contrast
allergies is acceptable. Adrenal replacement corticosteroid doses ≤10 mg daily
prednisone equivalent are permitted, as are topical, inhaled, intra-articular or
intra-nasal corticosteroids.
12. Participants with active Hepatitis B virus (HBV) hepatitis infection (defined as
having a positive hepatitis B surface antigen [HBsAg] test at Screening) or
Hepatitis C virus (HCV) hepatitis. Participants with resolved past HBV infection
(defined as having a negative HBsAg test and a positive antibody to hepatitis B core
antigen [anti-HBc] antibody test) are eligible. Participants positive for HCV
antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV
RNA.
13. Participants with active HIV infection or known history of HIV infection.
14. Active infection requiring systemic antibacterial, antiviral or anti-fungal therapy
for ≤ 7 days of first IMP administration. Note that participants on antibacterial,
anti-fungal or antiviral prophylaxis are eligible.
15. Uncontrolled or recent history of clinically significant cardiovascular disease:
Symptomatic heart failure (New York Heart Association classes II-IV), unstable
angina, myocardial infarction, serious/uncontrolled/unstable cardiac arrhythmia,
cerebral vascular accident, coronary/peripheral artery bypass graft surgery,
transient ischaemic attack, or pulmonary embolism within 4 months prior to first IMP
administration. Note that participants with small pulmonary emboli not thought to
put them at higher risk may be considered eligible on a case-by-case basis, in
discussion with the Sponsor.
16. Confirmed Baseline QTcF > 450 msec for males and > 470 msec for females (triplicate
ECG) or history of torsades de pointes or history of congenital long QT syndrome.
Note that participants with an apparent prolonged QT due to bundle branch block may
be considered eligible on a case-by-case basis, in discussion with the MM.
17. History of clinically significant interstitial lung disease, or active
non-infectious pneumonitis, or which may interfere with the detection or management
of suspected drug related pulmonary toxicity.
18. Has had or is scheduled to have major surgery < 28 days prior to the first IMP
administration. Elective surgical procedures not considered to put participants at
higher risk of AEs may be allowed on a case-by-case basis, in discussion with the
Sponsor.
19. Any other concurrent severe and/or uncontrolled medical, surgical or psychiatric
and/or social condition which, in the view of the Investigator, could compromise the
participant's safety or ability to participate in the study and make them unsuitable
for participation.
20. Use of other investigational medicinal products within 2 weeks or at least 5
half-lives (whichever is longer) before IMP administration.
21. Must not have had a live vaccine administration ≤ 28 days prior to the first dose of
the IMP.
22. Participants with known active or suspected alcohol or drug abuse that may interfere
with the study in the opinion of the Investigator.
23. Gastrointestinal conditions that may affect oral absorption of drugs in the opinion
of the Investigator, including but not restricted to gastroparesis and short bowel
syndrome.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Blacktown Hospital
Address:
City:
Blacktown
Zip:
2148
Country:
Australia
Facility:
Name:
Scientia Clinical Research
Address:
City:
Randwick
Zip:
2031
Country:
Australia
Facility:
Name:
Southern Oncology Clinical Research Unit (SOCRU)
Address:
City:
Adelaide
Zip:
5042
Country:
Australia
Facility:
Name:
Linear Clinical Research
Address:
City:
Nedlands
Zip:
6009
Country:
Australia
Start date:
October 21, 2024
Completion date:
October 30, 2027
Lead sponsor:
Agency:
Pathios Therapeutics Pty Ltd
Agency class:
Industry
Source:
Pathios Therapeutics Pty Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06634849
