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TH1902 in Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04706962
Recruitment Status : Recruiting
First Posted : January 13, 2021
Last Update Posted : April 1, 2021
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
Theratechnologies

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Solid Tumor TNBC - Triple-Negative Breast Cancer Pancreatic Cancer Colorectal Cancer Gynecologic Cancer Drug: TH1902 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model 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.

Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 4, 2021
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TH1902
TH1902 peptide-drug conjugate
Drug: TH1902
Intravenous infusion
Other Name: TH1902 peptide-drug conjugate




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: Through completion, an average of 12 weeks ]
    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.

  2. Maximum tolerated dose (MTD) of TH1902. [ Time Frame: Up to 21 days ]
    The MTD will be defined as the dose level at which no more than one of six patients experiences a dose limiting toxicity (DLT) after 21 days of treatment have occurred, with the next higher dose having at least 2 of 3 or 2 of 6 patients experiencing a DLT.

  3. Recommended Phase 2 Dose (RP2D) of TH1902. [ Time Frame: Up to 24 months ]
    The RP2D will be determined following the determination of the MTD and an overall assessment of safety as determined by the Safety Committee.


Secondary Outcome Measures :
  1. Efficacy in patients [ Time Frame: 6 weeks ]
    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).

  2. Plasma concentration [ Time Frame: 48 hours ]
    The plasma concentration will be measured as part of pharmacokinetic (PK) testing.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04706962


Contacts
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Contact: Theratechnologies 514-336-7800 communications@theratech.com

Locations
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United States, Pennsylvania
Gettysburg Cancer Center Recruiting
Gettysburg, Pennsylvania, United States, 17325
Contact: Vanessa Warner, RN    717-334-4033    info@gettysburgoncology.com   
Contact: Terry Burke, RN    (717) 334-4033    info@gettysburgoncology.com   
Principal Investigator: Satish Shah, MD         
Sponsors and Collaborators
Theratechnologies
PPD
Investigators
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Principal Investigator: Funda Meric-Burnstam, MD M.D. Anderson Cancer Center
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Responsible Party: Theratechnologies
ClinicalTrials.gov Identifier: NCT04706962    
Other Study ID Numbers: TH1902-CTR-0001
First Posted: January 13, 2021    Key Record Dates
Last Update Posted: April 1, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Colorectal Neoplasms
Pancreatic Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases