Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 1
SystImmune Inc. (Voir sur ClinicalTrials)
août 2023
juillet 2030
24 septembre 2026
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Anas GAZZAH | 26/10/2026 17:50:02 | Contacter | ||
Critères
Tous
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 <LLN - 3.0 mmol/L or equivalent)
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.