TH1902 in Patients With Advanced Solid Tumors

NCT04706962 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: TH1902-CTR-0001
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 6

Brief Summary

Open label first-in-human study of TH1902 in solid cancer, with 4 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, HR+ breast cancer, epithelial ovarian cancer, endometrial cancer, cutaneous melanoma, thyroid cancer, SCLC, prostate cancer and other cancers known to express SORT1 that are refractory to standard therapy. Part 3 (optimization): patients diagnosed with histologically or cytologically confirmed high grade serous ovarian cancer, including high grade peritoneal or fallopian tube cancer, or high grade endometrioid cancer, that is refractory or resistant to standard therapies, should not be considered platinum sensitive, and where current therapy is not considered to be providing benefit. Part 4 (basket expansion): selected cancer type diagnosed with histologically or cytologically confirmed cancers, where TH1902 has been studied and/or showed activity (in Parts 1 to 3), that is refractory or resistant to standard therapies, and where current therapy is not considered to be providing benefit.

Conditions

Solid Tumor; TNBC - Triple-Negative Breast Cancer; Hormone Receptor-positive Breast Cancer; Epithelial Ovarian Cancer; Endometrial Cancer; Cutaneous Melanoma; Thyroid Cancer; Small-cell Lung Cancer; Prostate Cancer; SORT1+ Cancers

Outcome Measures

Primary Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  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.

  Through completion, an average of 12 weeks

• Maximum tolerated dose (MTD) of TH1902.

  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.

  Up to 21 days

• Recommended Phase 2 Dose (RP2D) of TH1902.

  The RP2D will be determined following the determination of the MTD and an overall assessment of safety as determined by the Safety Committee.

  Up to 24 months

Secondary Outcomes (2)

• Efficacy in patients

  6 weeks

• Plasma concentration

  48 hours

Study Arms (1)

TH1902

EXPERIMENTAL

TH1902 peptide-drug conjugate

Drug: TH1902

Interventions

TH1902 DRUG

Intravenous infusion

Also known as: TH1902 peptide-drug conjugate

TH1902

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Parts 1, 2, 3 and 4
• Patients must meet all the following criteria to be eligible to participate in the study:
• Are ≥18 years old males or females.
• Are capable of understanding and have voluntarily signed the informed consent document and willing to comply with study requirements.
• Have measurable disease according to the RECIST 1.1.
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have an expected survival of at least 3 months.
• Have a negative pregnancy test result confirmed by a serum beta-human chorionic gonadotropin (β-HCG) test (for women of childbearing potential \[WOCBP\]) performed at Screening and have a negative pregnancy urine test result on Cycle 1, Day 1. This is not applicable to patients who are unable to become pregnant, including those with bilateral oophorectomy, salpingectomy, tubal ligation and/or hysterectomy or postmenopausal or those that have had definitive radiation therapy to the pelvis. WOCBP are considered postmenopausal if 12 months of spontaneous amenorrhea, or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone levels \> 40 mIU/mL, or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
• WOCBP who are sexually active with a non-sterilized male partner (sterilized males should be ≥6 months post vasectomy and have obtained documentation of the absence of sperm in the ejaculate) should agree to remain abstinent (refrain from sexual intercourse of any kind) 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 for both female and male patients, following the last dose of TH1902. Periodic abstinence (e.g., calendar, symptothermal, and post-ovulation), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.
• Effective contraceptive measures include the following:
• Intrauterine device (e.g., IUD) or intrauterine system plus one barrier method.
• Oral, intravaginal, or transdermal combined (estrogen and progestogen) hormonal contraceptive associated with the inhibition of ovulation plus one barrier method.
• Oral, implantable, or injectable progestogen-only hormonal contraceptive associated with the inhibition of ovulation plus one barrier method.
• Bilateral tubal occlusion at least 6 weeks before study drug administration.
• Sterilization of male partner (at least 6 months prior to screening). For WOCBP in on the study, the vasectomized male partner should be the sole partner for that patient and must have obtained documentation of the absence of sperm in the ejaculate.

You may not qualify if:

• Parts 1, 2, 3 and 4
• Patients who meet any one of the following criteria at baseline will be excluded from study participation:
• 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) must not have received their last dose within 4 weeks, or within 5 half-lives (whichever is shorter) prior to treatment with the study drug (Cycle 1, Day 1).
• Have known hypersensitivity to taxanes, including docetaxel, or to any excipients in the TH1902 study drug (e.g., polysorbate 80, predominantly known as Tween® 80).
• Have experienced severe toxicity with previous taxane treatment.
• Patients with leptomeningeal disease or spinal cord compression or active brain metastases are ineligible for enrollment. Patients with treated brain metastasis that are stable for 4 weeks or longer, and not requiring steroids, are eligible for treatment. Patients with history of brain metastasis should have a magnetic resonance imaging (MRI) within 4 weeks of initiating treatment. For patients where MRI is contraindicated (e.g., due to tissue expanders), brain computerized tomography (CT) may be obtained after discussion with Sponsor.
• Pregnant, breastfeeding, or planning to become pregnant during the treatment period.
• Had any acute viral (including COVID-19), bacterial, or fungal infection that requires parenteral therapy within 14 days prior to treatment with study drug (Cycle 1, Day 1).
• Have received a live vaccine within 30 days prior to administration of the study drug.
• Had treatment with cytochrome P450 CYP3A4 or CYP3A5 enzyme-inducing or enzyme inhibiting drugs within 14 days prior to treatment with the study drug (Cycle 1, Day 1).
• Have any of the following hematologic abnormalities at baseline:
• Hemoglobin: \<9 g/dL rounded value (90 g/L) for Parts 1 and 2; \<8 g/dL rounded value (80 g/L) for Parts 3 and 4. Patients may be transfused with packed red blood cells (within the 21-day screening period) prior to TH1902 infusion, if clinically warranted. A post-transfusion hemoglobin assessment may qualify the patient for participation.
• Absolute neutrophil count \< 1.5 x 109/L (1500/mm3)
• Platelet count \< 100 x 109/L (100,000/mm3)
• Have any of the following serum chemistry abnormalities at baseline:

Sponsors & Collaborators

• Theratechnologies: lead
• PPD Development, LP: collaborator
• Altasciences Company Inc.: collaborator
• Windtree Therapeutics: collaborator
• Syneos Health: collaborator
• Innovaderm Research Inc.: collaborator

Study Sites (6)

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Pennsylvania Cancer Specialists Research Institute

Gettysburg, Pennsylvania, 17325, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 0A9, Canada

Location

Related Publications (2)

• Charfi C, Demeule M, Currie JC, Larocque A, Zgheib A, Danalache BA, Ouanouki A, Beliveau R, Marsolais C, Annabi B. New Peptide-Drug Conjugates for Precise Targeting of SORT1-Mediated Vasculogenic Mimicry in the Tumor Microenvironment of TNBC-Derived MDA-MB-231 Breast and Ovarian ES-2 Clear Cell Carcinoma Cells. Front Oncol. 2021 Oct 22;11:760787. doi: 10.3389/fonc.2021.760787. eCollection 2021.

  PMID: 34751242 BACKGROUND

• Demeule M, Charfi C, Currie JC, Larocque A, Zgheib A, Kozelko S, Beliveau R, Marsolais C, Annabi B. TH1902, a new docetaxel-peptide conjugate for the treatment of sortilin-positive triple-negative breast cancer. Cancer Sci. 2021 Oct;112(10):4317-4334. doi: 10.1111/cas.15086. Epub 2021 Aug 12.

  PMID: 34314556 BACKGROUND

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Carcinoma, Ovarian Epithelial; Endometrial Neoplasms; Melanoma; Thyroid Neoplasms; Small Cell Lung Carcinoma; Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Funda Meric-Burnstam, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This first-in-human study is designed as a multi-center, open-label, with 4 sequential parts: Part 1 (dose escalation), Part 2 (dose expansion), Part 3 (dose optimization), Part 4 (basket expansion).

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 13, 2021
• Study Start: March 4, 2021
• Primary Completion: December 1, 2025
• Study Completion: January 1, 2026
• Last Updated: April 15, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (5)