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NCT05983432 | RECRUITING | Non Small Cell Lung Cancer

Evaluate BL-B01D1 in Patients With Metastatic or Unresectable Non-Small Cell Lung Cancer (NSCLC) and Other Solid Tumors
Sponsor:

SystImmune Inc.

Brief Summary:

The objective of this study is to evaluate the safety, tolerability, and efficacy of BL-B01D1 in patients with Metastatic or Unresectable Non-Small Cell Lung Cancer (NSCLC) and Other Solid Tumors.

Condition or disease

Non Small Cell Lung Cancer

Lung Cancer

Breast Cancer

Esophageal Cancer

Small Cell Lung Cancer

Nasopharyngeal Cancer

Head and Neck Squamous Cell Carcinoma

Prostate Adenocarcinoma

Ovarian Cancer

Endometrial Cancer

Cervical Cancer

Triple Negative Breast Cancer

Intervention/treatment

BL-B01D1

Phase

PHASE1

Detailed Description:

BL-B01D1-LUNG-101 is a global, multi-center, Phase 1 study to evaluate the safety, tolerability, pharmacokinetics , and initial efficacy of BL-B01D1 in participants with metastatic or unresectable NSCLC and Other Solid Tumors. This study will be conducted in two different dosing schedules (Cohort A and Cohort B) and three parts (dose escalation, dose finding and dose expansion). Cohort A will be dosed on Day 1 and Day 8 of a continuous 21-day treatment cycle. Cohort B will be dosed on Day 1 of a continuous 21-day treatment cycle. Each Cohort has different dose groups.

Study Type : INTERVENTIONAL
Estimated Enrollment : 470 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : A Phase 1 Study Evaluating the Safety, Tolerability, and Efficacy of BL-B01D1 in Subjects With Metastatic or Unresectable Non-Small Cell Lung Cancer and Other Solid Tumors
Actual Study Start Date : 2023-08-08
Estimated Primary Completion Date : 2026-12-31
Estimated Study Completion Date : 2028-03-21

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
Inclusion criteria
  • 1. Signed the informed consent voluntarily and agreed to follow the program requirements
  • 2. Either sex
  • 3. Age: ≥18 years
  • 4. Has a life expectancy of ≥3 months
  • 5. Has histologically documented, incurable, locally advanced or metastatic epithelial origin malignant cancer, priority to include the following tumor types: NSCLC, HER2 - breast cancer, esophageal cancer, SCLC, NPC, and HNSCC.
  • Has documented locally advanced or metastatic HER2 negative (by immunohistochemistry \[IHC\], score of 0 or 1) Hormone Receptor (HR) positive (HER2-, HR+) OR HER2 negative (IHC score of 0 to 2) HR negative breast cancer (HER2-, HR-) as per ASCO CAP criteria (ASCO CAP 2023; Wolff et al. 2023), not amenable to curative surgery or radiation with documentation of radiological disease progression while on/after receiving most recent treatment regimen for locally advanced or metastatic disease, must have received 1 prior line of chemotherapy for advanced disease and, when applicable and if approved in that region, a PD-1/PD-L1 inhibitor, either given concurrently or sequentially. When appropriate, must have progression on at least 1 prior line of hormonal therapy with or without a targeted therapy (such as CDK4/6, mTOR, or PI3-K inhibitors) administered for treatment of metastatic disease.
  • In Dose Escalation and Dose finding portions of the study, for triple-negative breast cancer (TNBC, HER2-/HR-) participants must have received PARP inhibitors if a BRCA mutation is present and sacituzumab govitecan as second line treatment. Participants who are HER2 low must have received trastuzumab deruxtecan.
  • 6. Agree to provide archived tumor samples (tissue block or slides) from primary or metastatic sites within 2 years. In the event that no archival tissue is available a fresh tissue biopsy is highly encouraged but not mandatory.
  • 7. Has at least one measurable lesion based on RECIST V1.1 (with the exception of Prostate adenocarcinoma cohort, where subjects with bone metastasis are allowed)
  • 8. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1
  • 9. Toxicity of previous antitumor therapy has returned to level ≤1 as defined by NCI-CTCAE V5.0 (except for asymptomatic laboratory abnormalities such as elevated ALP, hyperuricemia, elevated serum or plasma amylase/lipase, and elevated blood glucose; except for toxicity that the investigator determined to have no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, hypothyroidism stabilized by hormone replacement therapy, etc.)
  • 10. Has no serious cardiac dysfunction, left ventricular ejection fraction ≥50%
  • 11. Has adequate organ function before registration, defined as: a) Marrow Function: Absolute neutrophil count (ANC) ≥1.2×109 /L, Platelet count ≥100×109 /L, Hemoglobin (Hb) ≥90 g/L b) Hepatic function: Total bilirubin（TBIL≤1.5 ULN, AST and ALT without liver metastasis ≤2.5 ULN, AST and ALT with liver metastasis ≤5.0 ULN c) Renal function: Creatinine clearance ≥50 mL/min (According to the Cockcroft and Gault equation)
  • 12. Coagulation function: international normalized ratio (INR) ≤1.5×ULN, and activated partial thromboplastin time (APTT) ≤1.5 ULN
  • 13. Urinary protein ≤2+ or ≤1000mg/24 hours
  • 14. Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception during the course of the study and for 7 months for females and 4 months for males after the last dose of study treatment. An additional contraceptive method, such as a barrier method like a condom is required.
  • 15. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and must be nonlactating. Female subjects are considered WOCBP unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \>45 years old in the absence of other biological or physiological causes. In addition, females \<55 years old must have a serum follicle stimulating hormone (fsh) level \> 40 mIU/mL to confirm menopause.
  • 16. For subjects with NSCLC (EGFR mutation)
    • a) Evidence of documented EGFR TKI-sensitizing deletion mutation in EGFR Exon 19 (ex19del) or leucin-arginine substitution point mutation in EGFR Exon 21 (ex21L858R), the serine-isoleucine mutation in EGFR Exon 20 (ex20S768I), the leucine-glutamine substitution mutation in Exon 21 (ex21L861Q), or the glycine substitution (with alanine, cysteine, or serine) mutation in Exon 18 (ex18G719X) at or after the time of disease diagnosis and prior to initiation of treatment.
    • 17. For Triple-Negative Breast Cancer (TNBC, HER2-/HR-)
      • a) Histologically or cytologically confirmed and documented locally advanced, recurrent inoperable or metastatic TNBC
      • 18. For Esophageal adenocarcinoma
      • a) Has locally advanced or metastatic adenocarcinoma cell carcinoma of the esophagus or esophagogastric junction cancers, not amenable to curative surgery or radiation with documentation of radiological disease progression after one line of fluoropyrimidine and/or platinum-based chemotherapy treatment regimen for locally advanced or metastatic disease.
      • NOTE: Prior therapies such as trastuzumab, zolbetuximab, or IOs are allowed in the study.
      • 19. For Prostate adenocarcinoma
      • a) Subject has metastatic castration-resistant prostate cancer (mCRPC) after progression on/after an androgen receptor pathway inhibitors (ARPI) treatment, such as abiraterone, enzalutamide, apalutamide and darolutamide.
      • Note: No prior chemotherapy including docetaxel is allowed Prior treatment with lutetium Lu 177 vipivotide tetraxetan (Pluvicto) is allowed. Enrollment will be capped for lutetium Lu 177 vipivotide tetraxetan-naive participants at approximately 20 or participants with prior lutetium Lu 177 vipivotide tetraxetan treatment at approximately 20.
      • 20. For NSCLC (EGFR wild type) with squamous histology
      • 1. Has documented locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation with documentation of radiological disease progression while on/after receiving most recent treatment regimen for locally advanced or metastatic disease with predominantly squamous cell histology
      • 2. Must have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Must have no known genomic alterations in ROS proto-oncogene 1 (ROS1).
      • 3. Progressed or intolerant to one line of platinum-based chemotherapy with α-PD-1/L1 monoclonal antibody given either concurrently or sequentially.
      • 21. For NSCLC (EGFR wild type) with adenocarcinoma histology
      • 1. Has documented locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation with documentation of radiological disease progression while on/after receiving most recent treatment regimen for locally advanced or metastatic disease with predominantly adenocarcinoma histology
      • 2. Must have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Must have no known genomic alterations in ROS proto-oncogene 1 (ROS1).
      • Progressed or intolerant to one line of platinum-based chemotherapy with α-PD-1/L1 monoclonal antibody given either concurrently or sequentially.
      • 22. Ovarian adenocarcinoma
      • a) Has histologic documentation of epithelial ovarian, primary peritoneal, or fallopian tube cancer that has progressed or relapsed on or after a previous platinum-containing chemotherapy with or without a PARP inhibitor.
      • Note: participants with platinum-sensitive or platinum resistant recurrent ovarian cancer (PSR) are eligible. However, enrollment will be capped for platinum-sensitive or platinum resistant participants at approximately 20 each.
      • Prior bevacizumab treatment is allowed.
      • 23. Endometrial carcinoma
      • a) Has relapsed, advanced and/or metastatic endometrial carcinoma, who have progressed on or after prior platinum-based chemotherapy with or without immuno-oncology (IO) treatment
      • 24. For Cervical carcinoma Has relapsed, advanced and/or metastatic cervical carcinoma, who have progressed on or after prior platinum-based chemotherapy with or without immuno-oncology (IO) treatment
      • Exclusion criteria
        • 1. Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other anti-tumor therapy within 2 weeks or 5 half-lives (whichever is shorter) prior to the first administration; major surgery within 4 weeks prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration
        • 2. Participants with history of severe heart disease, such as symptomatic congestive heart failure (CHF) ≥ Grade 2 (CTCAE 5.0), New York Heart Association (NYHA) ≥ Grade 2 heart failure, history of transmural myocardial infarction, unstable angina pectoris etc;
        • 3. Subjects with prolonged QT interval (QTc \>470 msec), complete left bundle branch block, Grade 3 atrioventricular block
        • 4. Active autoimmune diseases and inflammatory diseases, such as: systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, etc., except for Type I diabetes, hypothyroidism that can be controlled only by standard of care treatment, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis)
        • 5. Other malignant tumors were diagnosed within 5 years prior to the first administration with the following exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after radical resection
        • 6. Participants with poorly controlled hypertension by two kinds of antihypertensive drugs (systolic blood pressure\>150 mmHg or diastolic blood pressure\>100 mmHg)
        • 7. Participants have Grade 3 lung disease defined according to NCI-CTCAE v5.0, a history of interstitial lung disease (ILD)/ pneumonitis
        • 8. Unstable thrombotic events such as deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring therapeutic intervention within the previous 6 months before screening; Infusion set-related thrombosis is excluded
        • 9. Participants with primary tumors in the central nervous system (CNS) and active or untreated CNS metastases and/or carcinomatous meningitis should be excluded. Participants with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks and have no evidence of new or enlarging brain metastases and no requirements for corticosteroids 14 days prior to dosing with the investigational product (IP). Participants on low dose corticosteroids (\<20 mg prednisone or equivalent/day) may participate.
        • 10. Participants who have a history of allergies to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of BL-B01D1
        • 11. Participants have a history of autologous or allogeneic stem cell transplantation (Allo-HSCT)
        • 12. Has received treatment with anthracyclines with a cumulative dose exceeding 360 mg/m2
        • 13. Participants with ≥ Grade 2 hypokalemia (low concentration of potassium in the blood) according to CTCAE v5.0 (Grade 1: participant asymptomatic with potassium levels \
        • 14. Known Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active Hepatitis B virus infection (HBV-DNA copy number\> the lower limit of detection) or active Hepatitis C virus infection (HCV antibody positive and HCV-RNA \> the lower limit of detection)
        • 15. Participants with active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis.
        • 16. Received an investigational drug within 4 weeks, or two half-lives (whichever is longer) prior to first dose of study treatment
        • 17. Participants who are pregnant or breastfeeding
        • 18. Other conditions that the investigator believes may make the subject not suitable for participating in this clinical trial.
        • 19. Participants who have received prior therapy with any ADC targeting EGFR and/or HER3 or containing a topoisomerase 1 inhibitor payload (all dose expansion cohorts with exception of TNBC noted below).
        • Note: For TNBC dose expansion cohort, participants with prior ADC therapy targeting HER3 and EGFR or a topoisomerase I inhibitor, such as sacituzumab govitecan may be enrolled with Sponsor consultation prior to enrollment
        • 20. For NSCLC EGFRmut
          • 1. Participants treated with more than two systemic chemotherapies prior to randomization.
          • NOTE: Progression of disease within 12 months after receiving neoadjuvant and adjuvant chemotherapies is considered 1 prior systemic chemotherapy
          • 2. Previously documented EGFR Exon 20 insertion mutations as primary EGFR mutations
          • 21. For Triple-Negative Breast Cancer (TNBC, HER2-/HR-)
            • a) Participants treated with more than two systemic chemotherapies prior to randomization.
            • NOTE: Progression of disease within 12 months after receiving neoadjuvant and adjuvant chemotherapies is considered 1 prior systemic chemotherapy
            • 22. For Esophageal Carcinoma a) Participants received more than 1 prior line of systemic chemotherapy therapy for locally advanced or metastatic disease. NOTE: this limit only applies to prior systemic chemotherapy.
            • 23. For Prostate adenocarcinoma
              • a) Prior treatment with systemic chemotherapy.
              • 24. For NSCLC with EGFR WT squamous or adenocarcinoma histology: a) Participants received more than 1 prior line of systemic chemotherapy for locally advanced or metastatic disease
              • 25. For Ovarian Carcinoma a) Participants received more than 1 prior line of systemic chemotherapy. Re-treatment with platinum-based chemotherapy is considered one line of therapy. Prior hormonal therapy is permitted.
              • 26. For Endometrial Carcinoma a) Participants received more than 1 prior line of systemic chemotherapy. Re-treatment with platinum-based chemotherapy is considered one line of therapy. Prior hormonal therapy is permitted.
              • 27. For Cervical Carcinoma a) if received more than 1 prior line of systemic chemotherapy. Re-treatment with platinum-based chemotherapy is considered one line of therapy.
              • Notes: Re-treatment with platinum-based chemotherapy is considered one line of therapy.
              • Note: A participant who does not meet this exclusion criterion may be allowed into the study pending the sponsor's approval, based on current accrual within this dose expansion cohort.
              • Note: There is no limit on the number of prior lines of non-chemotherapy regimens. ADCs with cytotoxic payloads are considered a line of chemotherapy. For any expansion cohorts, if only limited number of patients can be enrolled with 1 prior line of chemotherapy, the Sponsor has the option to allow participants with more than 1 prior line of chemotherapy to be enrolled, upon Sponsor's approval.
Evaluate BL-B01D1 in Patients With Metastatic or Unresectable Non-Small Cell Lung Cancer (NSCLC) and Other Solid Tumors

Location Details

NCT05983432

Please Choose a site

How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

United States, California

Beverly Hills Cancer Center

Beverly Hills, California, United States, 90211

RECRUITING

United States, California

City of Hope Cancer Center

Duarte, California, United States, 91010

NOT YET RECRUITING

United States, California

Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, United States, 92612

RECRUITING

United States, California

University of California Irvine Medical Center

Orange, California, United States, 92868

RECRUITING

United States, California

UCLA Santa Monica

Santa Monica, California, United States, 90404

RECRUITING

United States, Colorado

University of Colorado Cancer Center

Aurora, Colorado, United States, 80045

RECRUITING

United States, Connecticut

Yale University, Yale Cancer Center

New Haven, Connecticut, United States, 06520

RECRUITING

United States, District of Columbia

Georgetown University Medical Center

Washington D.C., District of Columbia, United States, 20007

RECRUITING

United States, Florida

Sylvester Comprehensive Cancer Center

Miami, florida, United States, 33125

RECRUITING

United States, Florida

Sara Cannon Research Institute Lake Nona

Orlando, florida, United States, 32827

RECRUITING

United States, Florida

Hematology - Oncology Associates of the Treasure Coast

Port Saint Lucie, florida, United States, 34952

RECRUITING

United States, Illinois

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States, 60611

RECRUITING

United States, Iowa

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States, 52242

RECRUITING

United States, Kentucky

Norton Cancer Institute

Louisville, Kentucky, United States, 40202

RECRUITING

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

RECRUITING

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

RECRUITING

United States, New York

Memorial Sloan Kettering Cancer Center Head Neck Services

New York, New York, United States, 10065

RECRUITING

United States, South Carolina

PRISMA Health/ITOR

Greenville, South Carolina, United States, 29605

RECRUITING

United States, Tennessee

Sarah Cannon - Tennessee Oncology

Nashville, Tennessee, United States, 37203

RECRUITING

United States, Texas

Oncology Consultants, P.A.

Houston, Texas, United States, 77030

RECRUITING

United States, Texas

University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States, 77030

RECRUITING

United States, Virginia

Virginia Cancer Specialists

Fairfax, Virginia, United States, 22031

RECRUITING

United States, Washington

University of Washington Fred Hutchinson

Seattle, Washington, United States, 98109