Trial Title:
Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmocodynamics and Preliminary Antitumor Activity of AT-1965 in Patients with Advanced, Refractory or Recurrent Solid Tumors
NCT ID:
NCT06234098
Condition:
Solid Tumor
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
Advanced Solid Tumors
Refractory Solid Tumors
Recurrent Solid Tumors
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AT-1965 Liposome Injection
Description:
AT-1965 Liposome Injection administered intravenously once weekly for the first 3 weeks
(Days 1, 8 and 15) of a 4 week cycle.
Arm group label:
AT-1965 Liposome Injection
Summary:
This is a first-in-human, multicenter, open-label, dose escalation and dose expansion
Phase 1/2 study to determine the MTD and/or the recommended Phase 2 dose (RP2D) and to
characterize DLTs of AT-1965 as well as to investigate the safety, pharmacokinetics (PK),
pharmacodynamics, and preliminary antitumor activity of AT-1965 in patients with
advanced, refractory or recurrent solid tumors (nonresectable and/or metastatic)
including mTNBC.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. The patient has a histologically or cytologically confirmed unresectable or
metastatic solid tumor that is refractory to standard therapy or for which in the
opinion of the investigator no standard therapy is suitable.
2. Patient should have at least 1 measurable lesion per RECIST version 1.1 as assessed
by the investigator. For Part A only, patients with radiographically evaluable but
non-measurable disease are allowed after discussion with the sponsor.
3. Recovered from AEs (except irAEs) of prior chemotherapy (per NCI CTCAE version 5.0)
to Grade ≤ 1 or return to baseline status (except for alopecia) as per
Investigator's discretion.
4. The patient has an ECOG performance status of 0 to 2.
5. The patient has adequate bone marrow, renal, and hepatic function, defined as
follows:
1. Hemoglobin ≥9.5 g/dL (without transfusion in the prior 3 weeks).
2. Platelets ≥100 × 109 cells/L (may be achieved with transfusion as per PI
discretion)
3. ANC ≥1.5 ×109 cells/L (without the use of hematopoietic growth factors within 4
weeks prior to dosing).
4. Creatinine Clearance ≥60 mL/min (by using Cockcroft-gault equation)
5. Total bilirubin ≤1.5 × ULN, unless the patient has a prior history of Gilbert's
syndrome, in which case ≤3.0 × ULN is acceptable.
6. AST and ALT ≤2.5 × ULN; or ≤5 × ULN if due to liver involvement by tumor
6. Female patients of child-bearing potential must have a negative serum pregnancy test
within 72 hours prior to the first dose of study drug and before each start of a new
treatment cycle. NOTE: Women are considered of childbearing potential unless they
are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or
bilateral oophorectomy) or are postmenopausal (at least 12 consecutive months with
no menses without an alternative medical cause) and have an elevated
follicle-stimulating hormone (FSH) at screening.
7. Female patients of childbearing potential must agree to use a highly effective
method of contraception during the study and for a minimum of 3 months following
administration of study drug, which includes a barrier method plus 1 or more of the
following:
1. Hormonal contraceptives (e.g., birth control pills, skin patches, vaginal
rings, or the Depo-Provera® shot)
2. Intrauterine device (IUD)
3. Male or female condoms with spermicide
4. Diaphragm with spermicide
5. Permanent tubal occlusive birth control system
8. Male patients with female partners of childbearing potential must be vasectomized or
be willing to use an acceptable method of birth control or to practice abstinence
during the study and for 3 months after the last dose of IMP.
9. Must be 30 days since participation in any other interventional clinical trial.
10. Must be 28 days since mRNA Covid 19 vaccine injection.
11. Willing to avoid sun exposure, wear protective clothing, and/or apply broad spectrum
(ultraviolet A [UVA] and ultraviolet B [UVB] protection) sunscreen if sun exposure
is unavoidable.
12. The patient is capable of understanding the written informed consent, provides
signed and witnessed written informed consent and authorization permitting use of
collected tissue and personal health information, and agrees to comply with protocol
requirements.
For Part B Dose Expansion in TNBC only:
1. Histologically or cytologically confirmed metastatic triple-negative breast cancer
(mTNBC) who had received at least two prior treatments (a taxane and sacituzumab
govitecan-hziy) for metastatic disease, for advanced disease.
2. In addition, patients with TNBC with either Low HER2 (IHC 1+ or IHC 2+/in situ
hybridization-negative), PD-L1 (CPS>10) or BRCA mutation need to have prior FDA
approved available therapies before participation in this expansion arm.
Exclusion Criteria:
1. The patient has an uncontrolled or life-threatening, symptomatic, current or
recurrent disease (e.g., cardiovascular, renal, hepatic, endocrine) or other
abnormality that could affect the action, absorption, or disposition of the study
drug, may impact the ability of the patient to participate, may affect clinical or
laboratory assessments, or otherwise has the potential to confound the study
results.
2. Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function,
unstable pulmonary condition) or any important medical or psychiatric illness or
abnormal laboratory finding that would, in the Investigator's judgment, increase the
risk to the patient associated with his or her participation in the study.
3. Uncontrolled diabetes.
4. Patients with a history of autoimmune disease. Excluded autoimmune conditions are
listed in Appendix 1.
1. Patients with history of transient autoimmune manifestations of an acute
infectious disease that resolved upon treatment of the infectious agent are not
excluded (e.g. acute Lyme arthritis).
2. Please contact the medical monitor regarding any uncertainty over autoimmune
exclusions.
5. History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonitis
(including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans,
cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on chest
computed tomography scan in the last 6 months; NOTE: history of radiation
pneumonitis in the radiation field (fibrosis) is permitted.
6. History of hemolysis or hemolytic anemia.
7. Evidence of ongoing subclinical hemolysis (high LDH and low serum haptoglobin with
increased reticulocyte count).
8. History of adrenal gland disorders such as Cushing Syndrome, Congenital adrenal
hyperplasia, Addison's Disease and hyperaldosteronism
9. Recipient of an allogeneic bone marrow transplantation or solid organ
transplantation.
10. Endocrinopathy, unless on stable hormone replacement therapy.
11. History of known human immunodeficiency virus (HIV); unresolved viral hepatitis as
documented by the detection of hepatitis B surface antigen (HBsAg), hepatitis C
virus (HCV) antibody at the time of the screening visit, and known quantitative HCV
RNA results greater than the lower limits of detection of the assay.
12. Clinically significant cardiovascular disease including:
- Myocardial infarction or stroke within 6 months prior to the initiation of
study treatment.
- LVEF <50% on baseline assessment.
- If patient enrolled with cardiovascular disease, the LVEF must be confirmed at
screening by and echocardiogram or MUGA.
- Unstable angina within 6 months prior to the initiation of study treatment.
- Congestive heart failure or cardiomyopathy with New York Heart Association
Class 2, 3 or 4 by clinical assessment or by imaging studies within 6 months
prior to the initiation of study treatment.
- Coronary or peripheral artery bypass graft surgery, transient ischemic attack,
or pulmonary embolism (in past 3 months).
- History of clinically significant ventricular arrhythmias (e.g., ventricular
tachycardia, ventricular fibrillation, torsades de pointes).
- Uncontrolled hypertension where the Systolic is ≥150 mmHg and the diastolic
blood pressure ≥110 mm Hg despite ongoing antihypertensive therapy.
- QT interval corrected by the Fridericia correction formula (QTcF) ≥470 msec on
the Screening ECG.
- The patient has cardiac dysrhythmias.
- The patient requires the use of concomitant medications that prolong QT/QTc
interval (except the patients who have normal ECG but are taking medications
that prolong QT/QTc interval).
13. Recent anticancer treatment, including the following (patient may be started earlier
within these timeframes if considered by the Investigator to be safe and within the
best interest of the patient and with approval from the Sponsor):
- Systemic antineoplastic therapy within 21 days or 5 half-lives prior to
initiation of study treatment. (6 weeks for nitrosoureas or mitomycin C and 8
weeks for platinum based drugs) and/or has not recovered from acute toxicity
for the most recent antitumor treatment to CTCAE Grade 1 or baseline, except
for alopecia, prior to the first dose of study drug.
- Radiation therapy within 2 weeks prior to the initiation of study treatment
- Patient received chemoembolization or radioembolization within 4 weeks prior to
the initiation of study treatment.
14. The patient has received any investigational agents that have not received
regulatory approval within 30 days or 5 half-lives prior to the first dose of study
drug, whichever is shorter. This includes the FDA approved for all Emergency
Authorization Use (EAU) drugs or therapies.
15. Major surgery within 4 weeks of starting study treatment or not recovered from any
effects of prior major surgery (uncomplicated central line placement or fine needle
aspirate are not considered major surgery).
16. Primary tumor type:
- Central nervous system (CNS) malignant disease not previously treated, active
leptomeningeal disease, uncontrolled symptomatic CNS involvement, or CNS
malignant disease requiring steroid or other therapeutic intervention.
- Liquid/hematological tumors
- Lymphoma
- Uveal melanoma
17. Patients with a history of secondary malignancy(ies) that is currently clinically
significant and has potential for metastases or currently requires active
intervention (except for gonadotropin-releasing hormone (GnRH) or luteinizing
hormone-releasing hormone (LH-RH) agonists in prostate cancer or hormonal therapy in
breast cancer).
- Secondary malignancies exceptions include basal cell or squamous cell skin
cancer
18. Requires systemic treatment with either corticosteroids (> 10 mg daily prednisone
equivalent) or other immunosuppressive medications within 14 days prior to Day 1 of
treatment. Inhaled, intranasal, intra-articular and topical (including ocular)
steroids are allowed. Adrenal replacement (i.e., physiologic replacement) doses > 10
mg daily prednisone equivalents are permitted in the absence of active autoimmune
disease.
19. History of severe immune-related AE (irAE) that led to permanent discontinuation of
prior immunotherapy.
20. History of Grade ≥ 3 irAE within the past 16 weeks or any Grade 4 life threatening
irAE (regardless of duration) or neurologic or ocular AE of any grade while
receiving prior immunotherapy; NOTE: Patients with endocrine AEs of any grade are
permitted to enroll if they are stably maintained on appropriate replacement therapy
but must have no history of adrenal crisis and be asymptomatic.
21. Has, within 28 days prior to screening, received a live, attenuated or mRNA based
vaccine against infectious disease.
22. Nursing women not willing to stop breastfeeding while on study and for 3 months
thereafter.
23. Uncontrolled active infection requiring intravenous (IV) antibiotic, antiviral, or
antifungal medications within 14 days prior to first dose of study treatment.
Patients on chronic suppressive antibiotics may be allowed after discussion with the
Sponsor.
24. Patient is <18 years of age at the time of informed consent.
25. Life expectancy of <3 months.
26. Known current drug or alcohol abuse.
27. The patient is not an appropriate candidate for participation in this clinical study
for any other reason as deemed by the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
CBCC Global Research Site 001
Address:
City:
Scottsdale
Zip:
85258
Country:
United States
Status:
Recruiting
Facility:
Name:
CBCC Global Research Site 005
Address:
City:
Bakersfield
Zip:
93309
Country:
United States
Status:
Recruiting
Facility:
Name:
CBCC Global Research Site 007
Address:
City:
El Segundo
Zip:
90245
Country:
United States
Status:
Recruiting
Facility:
Name:
CBCC Global Research Site 003
Address:
City:
Stanford
Zip:
94305
Country:
United States
Status:
Recruiting
Facility:
Name:
CBCC Global Research Site 002
Address:
City:
Portland
Zip:
97239
Country:
United States
Status:
Recruiting
Facility:
Name:
CBCC Global Research Site 006
Address:
City:
Dallas
Zip:
75230
Country:
United States
Status:
Recruiting
Start date:
February 13, 2024
Completion date:
January 2027
Lead sponsor:
Agency:
Alyssum Therapeutics
Agency class:
Industry
Collaborator:
Agency:
CBCC Global Research
Agency class:
Other
Source:
Alyssum Therapeutics
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06234098
