Description:
Open label first-in-human study of TH1902 in solid cancer, with 2 sequential parts:
Part 1 (dose escalation): patients with recurrent advanced solid tumors (all comers) that
have relapsed or are refractory to standard chemotherapy, surgery, radiation therapy, and for
which no known effective therapies exist.
Part 2 (expansion): selected patient populations with recurrent advanced TNBC, gynecological
cancer (epithelial ovarian or endometrial cancer), colorectal cancer and pancreatic cancer
that have relapsed or are refractory to standard chemotherapy, surgery, radiation therapy,
and for which no known effective therapies exist.
Title
- Brief Title: TH1902 in Patients With Advanced Solid Tumors
- Official Title: A Phase 1, Open-Label, Dose Escalation Study of TH1902 in Patients With Advanced Solid Tumors and Expansion in Patients With Triple Negative Breast Cancer (TNBC), Gynecological Cancer, Colorectal Cancer, and Pancreatic Cancer
Clinical Trial IDs
- ORG STUDY ID:
TH1902-CTR-0001
- NCT ID:
NCT04706962
Conditions
- Solid Tumor
- TNBC - Triple-Negative Breast Cancer
- Pancreatic Cancer
- Colorectal Cancer
- Gynecologic Cancer
Interventions
Drug | Synonyms | Arms |
---|
TH1902 | TH1902 peptide-drug conjugate | TH1902 |
Purpose
Open label first-in-human study of TH1902 in solid cancer, with 2 sequential parts:
Part 1 (dose escalation): patients with recurrent advanced solid tumors (all comers) that
have relapsed or are refractory to standard chemotherapy, surgery, radiation therapy, and for
which no known effective therapies exist.
Part 2 (expansion): selected patient populations with recurrent advanced TNBC, gynecological
cancer (epithelial ovarian or endometrial cancer), colorectal cancer and pancreatic cancer
that have relapsed or are refractory to standard chemotherapy, surgery, radiation therapy,
and for which no known effective therapies exist.
Detailed Description
This first-in-human study is designed as a multi-center, open-label, with 2 sequential parts:
Part 1 (dose escalation): will comprise patients with recurrent advanced solid tumors (all
comers) that have relapsed or are refractory to standard chemotherapy, surgery, radiation
therapy, and for which no known effective therapies exist.
Part 2 (expansion): will comprise selected patient populations with recurrent advanced TNBC,
gynecological cancer (epithelial ovarian or endometrial cancer), colorectal cancer and
pancreatic cancer that have relapsed or are refractory to standard chemotherapy, surgery,
radiation therapy, and for which no known effective therapies exist.
The PK profiles of TH1902 and free docetaxel will be evaluated for all patients in Parts 1
and 2. Once the MTD has been reached in Part 1, patients with TNBC, gynecological cancer
(epithelial ovarian or endometrial cancer), colorectal cancer and pancreatic cancer (10
patients per cancer type) will be enrolled in Part 2 and treated at the MTD or RP2D to
further assess the safety and tolerability of TH1902. The preliminary anti-tumor activity of
TH1902 will be evaluated for all patients as per the response evaluation criteria in solid
tumors (RECIST 1.1; Eisenhauer, 2009).
The study will use a modified rapid dose-escalation design as described by Simon et al.
(1997). A starting dose of 30 mg/m2 is proposed based on the available data for TH1902 and
the known safety profile of docetaxel.
Dose escalation by dose-doubling will be done for the first 2 dose levels, followed by a
modified Fibonacci dose escalation scheme (i.e. dose increases of 67%, 50%, 40% and 33%)
thereafter for each dose level. Patients in Part 1 will be observed for 21 days post Cycle 1
Day 1 drug administration for dose limiting toxicity (DLT). Dose escalation to the next dose
level will proceed following satisfactory review of safety data until the MTD is reached. The
MTD is defined as that dose-level at which ≤1 of 6 patients in a cohort develop an emergent
DLT.
Once the MTD has been defined, patients with TNBC, gynecological cancer (epithelial ovarian
or endometrial cancer) colorectal cancer and pancreatic cancer may be treated at the MTD or
Recommended Phase 2 Dose (RP2D), to further assess the safety and tolerability of TH1902, and
the preliminary anti-tumor activity of TH1902.
Trial Arms
Name | Type | Description | Interventions |
---|
TH1902 | Experimental | TH1902 peptide-drug conjugate | |
Eligibility Criteria
Inclusion Criteria:
Patients must meet all the following inclusion criteria within 21 days of study
participation (Cycle 1, Day 1) in order to be eligible to participate in the study:
1. Are ≥18 years old males or females.
2. Are capable of understanding and have voluntarily signed the informed consent document
and willing to comply with study requirements.
3. Have histologically or cytologically confirmed diagnostic of metastatic cancer or
advanced-stage solid tumor that has progressed following standard therapy or for
which, in the opinion of the Investigator, no standard effective therapy is available
or the patient has a contraindication to or declines standard therapy.
4. Have measurable disease according to the Response Evaluation Criteria in Solid Tumors
(RECIST 1.1).
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
6. Have an expected survival of at least 3 months.
7. Have a negative pregnancy test result at screening confirmed by a serum beta-human
chorionic gonadotropin (β-HCG) (for women of childbearing potential (WOCBP); not
applicable to patients who are unable to become pregnant, including those with
bilateral oophorectomy, salpingectomy and/or hysterectomy or postmenopausal [no menses
for the previous 12 months]) or those that have had definitive radiation therapy to
the pelvis. The test must be performed within 1 week before Day 1 of treatment.
8. WOCBP who are sexually active with a nonsterilised male partner (sterilised males
should be ≥1 year postvasectomy and have confirmed that they have obtained
documentation of the absence of sperm in the ejaculate) and male patients whose sexual
partners are WOCBP should agree to remain abstinent (refrain from heterosexual
intercourse) or use 2 effective methods of contraception, including at least 1 method
with a failure rate of <1% per year, during the treatment period and for at least 6
months and 3 months for female and male patients, respectively, following the last
dose of TH1902.
• Effective contraceptive measures include the following:
- Intrauterine device (e.g. IUD) plus one barrier method.
- Oral, implantable or injectable contraceptive plus one barrier method.
- Two barrier methods. Effective barrier methods are male or female condoms,
diaphragms and spermicides (cream or gel that contains a chemical to kill sperm).
9. WOCBP must agree to not donate ova and agree to ongoing pregnancy testing during the
course of the study and 6 months following the last dose of TH1902. Male patients must
refrain from donating sperm during the course of the study and 3 months following the
last dose of TH1902.
10. Male patients with pregnant female partners, must agree to remain abstinent or use a
condom (latex condom is recommended) during the treatment period and for at least 3
months after the last dose of TH1902 to avoid exposing the embryo, even if he has
undergone a successful vasectomy.
11. Patients with HIV/HBV/HBC will not be excluded from entry into the study provided the
following criteria are met:
- Patients with HIV infection must have CD4+ T-cell (CD4+) counts ≥ 350 cells/µL.
- The following eligibility criteria are for patients with evidence of chronic HBV
infection or patients with history of chronic HCV or who are virologically
suppressed on HCV treatment
- Liver-related laboratory eligibility criteria should be the same as that for
the general population.
- Exceptions: AST/ALT and bilirubin criteria may be less stringent in patients
with cancers such as hepatocellular carcinoma and cholangiocarcinoma in whom
hepatic function based on Child-Pugh score should be used.
- Patients with chronic HBV infection with active disease who meet the
criteria for anti HBV therapy should be on a suppressive antiviral therapy
prior to initiation of cancer therapy.
- Patients on concurrent HCV treatments must have HCV below the limit of
quantification.
- Patients with untreated HCV may be enrolled if the HCV is stable, the
patient is not at risk for hepatic decompensation, and the investigational
cancer treatment is not expected to exacerbate the HCV infection.
- Patients with chronic HBV infection with active disease who meet the criteria for
anti HBV therapy should be on a suppressive antiviral therapy prior to initiation
of cancer therapy.
- Patients with a history of HCV infection should have completed curative antiviral
treatment and HCV viral load must be below the limit of quantification. For
incurable cancers, patients with untreated HCV may be enrolled if the HCV is
stable, the patient is not at risk for hepatic decompensation, and the
investigational cancer treatment is not expected to exacerbate the HCV infection.
Patients must meet the following additional criterion to enter in Part 2:
1. Histologically or cytologically confirmed TNBC, gynecological cancer (epithelial ovarian
or endometrial cancer), colorectal cancer, or pancreatic cancer, and for which no standard
effective therapy is available.
Exclusion Criteria:
Patients who meet any one of the following criteria at baseline will be excluded from study
participation:
1. Have received chemotherapy, biologic therapy, immunotherapy, radiotherapy (except
palliative radiation delivered to <20% of bone marrow), or investigational agents
within 4 weeks before the first dose of study drug. Patients who have received
targeted therapy (investigational or approved) will not have received their last dose
within 4 weeks, or within 5 half-lives (whichever is shorter).
2. Have known hypersensitivity to docetaxel or to any excipients in the TH1902
investigational medicinal product (IMP) (e.g. polysorbate 80, predominantly known as
Tween® 80).
3. Have severe toxicity with previous taxane treatment.
4. Any past or current history of brain, leptomeningeal or spinal metastases.
5. Are pregnant or breastfeeding.
6. Had any acute viral (including COVID-19), bacterial, or fungal infection that requires
parenteral therapy within 14 days prior to study treatment (Cycle 1, Day 1).
7. Have received a live vaccine within 30 days prior to administration of the IMP.
8. Had treatment with cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2C8 (CYP2C8)
enzyme-inducing or enzyme inhibiting drugs within 14 days prior to treatment with the
IP (Cycle 1 Day 1) (Refer to Appendix 3).
9. Have any of the following hematologic abnormalities at baseline:
- Hemoglobin <9.0 g/dL (90 g/L)*
- ANC <1.5 x 109/L (1500/mm3)
- Platelet count <100 x 109/L (100,000/mm3) *Patients may be transfused with packed
red blood cells prior to TH1902 infusion, if clinically warranted. A
post-transfusion hemoglobin assessment may qualify the patient for participation.
10. Have any of the following serum chemistry abnormalities at baseline:
- Bilirubin >ULN.
- ALK Phos >2.5 with an aspartate aminotransferase (AST) and/or alanine
aminotransferase (ALT) >1.5 times the ULRR, or >5 times ULRR for patients with
documented liver metastases.
- Serum calcium above ULRR.
- Creatinine clearance (calculated according to the Cockcroft & Gault formula
(Cockcroft, 1976)) < 60 mL/ min):
- Female CrCl = (140 - age in years) × weight in kg × 0.85 / (serum creatinine
in mg/dL x 72)
- Male CrCL = (140 - age in years) × weight in kg × 1.00 / (serum creatinine
in mg/dL x 72)
11. Baseline corrected interval between Q and T waves on electrocardiogram (ECG) (QTc) ≥
470 msec using Fridericia's formula.
12. Have unstable or uncompensated respiratory, cardiac, hepatic or renal disease or any
other organ system dysfunction, medical condition, or laboratory abnormality which, in
the opinion of the Investigator, would either compromise the patient's safety or
interfere with the evaluation of the IMP.
13. Have evidence of persistent grade 2 or greather neurotoxicity.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) |
Time Frame: | Through completion, an average of 12 weeks |
Safety Issue: | |
Description: | Toxicities will be assessed in each patient by tracking the occurrence of graded Adverse Events (AEs). AEs will be graded according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v5.0. |
Secondary Outcome Measures
Measure: | Efficacy in patients |
Time Frame: | 6 weeks |
Safety Issue: | |
Description: | Anti-tumor activity (efficacy) will be assessed in all patients. Determination of the antitumor activity of TH1902 as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). |
Measure: | Plasma concentration |
Time Frame: | 48 hours |
Safety Issue: | |
Description: | The plasma concentration will be measured as part of pharmacokinetic (PK) testing. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Theratechnologies |
Last Updated
April 1, 2021