Study of ASN004 in Patients With Advanced Solid Tumors

Sponsor

Asana BioSciences (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04410224

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

14.3

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Participants in this study will receive ASN004 once every 3 weeks by intravenous infusion. The study will test various doses of ASN004 to find out the highest safe dose to test in future trials.

Eligible subjects will be sequentially enrolled in cohorts at escalated doses. There will be up to 43 evaluable patients in about seven dose levels with up to six subjects per dose level.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Breast Neoplasms Breast Adenocarcinoma Breast Cancer Recurrent Breast Cancer Metastatic Breast Cancer Invasive Non-small Cell Lung Cancer Non-small Cell Carcinoma Non-small Cell Lung Cancer Recurrent Non-Small Cell Squamous Lung Carcinoma Non-Small Cell Adenocarcinoma Non-small Cell Lung Cancer Metastatic Colorectal Cancer Colorectal Neoplasms Colorectal Carcinoma Colorectal Adenocarcinoma Colorectal Cancer Metastatic Colorectal (Colon or Rectal) Cancer Colon Cancer Colon Neoplasm Ovarian Cancer Ovarian Neoplasm Ovarian Cancer Recurrent Carcinoma, Ovarian Epithelial Carcinoma Ovary Carcinoma Colon Carcinoma Breast Carcinoma, Non-Small-Cell Lung	Drug: ASN004	Phase 1

Detailed Description

Eligible patients will be sequentially enrolled sequentially in an accelerated titration design study. Initial dose cohorts will contain single patients and dose escalation of no more than 100%. After the observation of a dose limiting toxicity (DLT), or the second Grade 2 adverse event, or at dose level 4 (12 mg/m2), the study will switch to a 3+3 design with 3-6 patients per cohort. pharmacodynamics (PD) data.

Dose escalation decisions will be based on the review of clinical safety and pharmacokinetic (PD) and pharmacodynamics (PD) data, and agreed upon by the Sponsor and investigators.

The maximum tolerated dose (MTD) will have an estimated DLT rate of < 33%. Cohorts may be expanded at any dose level or at the MTD for further evaluation of safety, or PK parameters as required.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

43 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

Escalating doses of ASN004Escalating doses of ASN004

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open Label, Multicenter, Dose-Finding Clinical Phase 1 Study of ASN004 to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy in Patients With Advanced Malignant Solid Tumors

Actual Study Start Date :

Dec 10, 2021

Anticipated Primary Completion Date :

Dec 9, 2022

Anticipated Study Completion Date :

Mar 12, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ASN004 ascending doses Patients will receive escalating doses of ASN004 to identify the best dose for further study.	Drug: ASN004 ASN004 is an antibody-drug conjugate for the treatment of advanced or metastatic solid tumors.

Arm

Intervention/Treatment

Experimental: ASN004 ascending doses

Patients will receive escalating doses of ASN004 to identify the best dose for further study.

Drug: ASN004

ASN004 is an antibody-drug conjugate for the treatment of advanced or metastatic solid tumors.

Outcome Measures

Primary Outcome Measures

Determine the maximum tolerated dose of ASN004 [first 21 days]
The MTD will be determined by evaluating the number of subjects with treatment related adverse events (AEs) and DLTs.

Secondary Outcome Measures

Calculate the pharmacokinetic (PK) area under the plasma concentration of ASN004 [First 63 days]
Calculate the amount of ASN004 in the bloodstream
Calculate the maximum plasma concentration at steady state [First 63 days]
Calculate the maximum amount of ASN004 in the bloodstream
Calculate the terminal elimination rate of ASN004 [First 63 days]
Calculate how fast ASN004 leaves the body
Change in the size of measurable tumor lesions [up to 1 year]
Change from baseline in the sum of the longest dimension in millimeters or each measurable lesion
Change in the status of non-measurable tumor lesions [Up to 1 year]
Number of subjects that have resolution on non-measurable tumor lesions
Appearance of new tumor lesions [Up to 1 year]
Number of subjects with new lesions

Other Outcome Measures

Correlate 5T4 oncofetal protein (5T4) expression and clinical efficacy [Up to 1 year]
Number of patients with 5T4 expression that have a complete response, partial response or prolonged stable disease when receiving ASN004.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Provide written, voluntary informed consent prior to any -study specific procedure.
Histologically confirmed diagnosis of advanced malignant solid tumor.
All patients must be willing to undergo tumor biopsy, preferably of the primary tumor, within 28 days prior to Cycle 1 Day 1. If the Investigator determines that the tumor is inaccessible for biopsy, archived tumor material collected within the last 12 months may be submitted.
Evidence of progressive disease.
Minimum life expectancy of at least 3 months, in the judgment of the Investigator.
Failure of standard therapy or no standard therapy available.
Presence of at least 1 measurable target lesion by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 excluding previously irradiated lesions, bone metastasis, or pleural effusion as sole manifestations of disease.
Patient's most recent therapy must have been completed within the following limits prior to the first dose of study drug:
prior cytotoxic chemotherapy treatments at least 3 weeks prior to first dose of study drug.
Completion of prior targeted anticancer treatments at least 2 weeks or 5 -half-lives prior to first dose of study drug, whichever is longer.
Completion of prior immuno-oncology treatments at least 3 weeks prior to first dose of study drug.
Patients must have recovered from any AE related to prior anticancer therapy to Grade 1 or less except for alopecia.
Age of at least 18 years old.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
A male patient must agree to use contraception as detailed in this protocol during the treatment period and for at least 3 months after the last dose of study treatment and refrain from donating sperm during this period.
A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies.

Not a woman of childbearing potential (WOCBP) OR ii. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of study treatment.

Adequate organ function as determined by the following criteria:
Hemoglobin ≥ 9.0 g/dL.
Absolute neutrophil count ≥ 1.5 × 109/L.
Platelet count ≥ 100 × 109/L.
Serum creatinine ≤ 1.5 × upper limit of normal (ULN) AND calculated creatinine clearance of > 60 mL/min.
Aspartate aminotransferase (AST; serum glutamic oxaloacetic transaminase) and alanine aminotransferase (ALT; serum glutamic-pyruvic transaminase) ≤ 3× ULN (or ≤ 2.5 × ULN if liver metastases).
Total bilirubin ≤ 1.5 x ULN.
Albumin ≥ 2.5 g/dL.
Activated partial thromboplastin time, prothrombin time, and international normalized ratio within normal limits unless anticoagulated for VTE treatment/prophylaxis at stable dose.
Patient is willing and able to comply with all protocol required visits and assessments.

Exclusion Criteria

Hematologic malignancies and lymphomas.
Known hypersensitivity to ASN004, its components, or its excipients.
Prior allergic reaction to recombinant human or murine proteins or known history of human anti-human or anti-murine antibody formation.
Known central nervous system (CNS) metastasis.
Known bleeding diathesis.
History of or active hepatitis B or hepatitis C infection.
Major surgery within 30 days prior to the start of study medication.
Infection requiring intravenous antibiotics within 14 days prior to the start of study medication.
Serious concurrent medical conditions, such as:
Clinically significant history of cardiovascular disease such as congestive heart failure New York Heart Association Class III or IV or uncontrolled hypertension at Screening.
12-Lead electrocardiogram (ECG) abnormalities considered by the Investigator to be clinically significant including QTcF ≥ 450 milliseconds at Screening (abnormal ECG confirmed by repeat assessment).
Severe dyspnea at rest or requiring oxygen therapy.
Active pneumonitis or interstitial lung disease.
Biliary obstruction, biliary blockage, and biliary stents.
Radiation therapy exceeding more than 5 Gray to the mediastinum/heart.
Patients with known history of left ventricular ejection fraction of < 50%.
Receipt of any investigational treatment within 4 weeks prior to the start of study medication.
Any previous treatment with antibody drug conjugate (ADC).
Prior participation, i.e., receipt of study medication, in this study.
Any condition that may impair the patient's ability to comply with study procedures or impact that ability to interpret study results.
Active and clinically significant bacterial, fungal, and viral infection such as immunodeficiency virus.
Female patients who are pregnant or breastfeeding or intend to become pregnant during their participation in the study or male patients who intend to father a child during their participation in the study.
History of another invasive malignancy that has not been in remission for at least 2 years. Exceptions to the -2-year limit include non-melanoma skin cancer, ductal carcinoma in situ, and cervical cancer in situ.
Any medical history, laboratory, imaging, ECG, or other findings that, in the opinion of the Investigator, the Sponsor or Contract Research Organization (CRO) Medical Monitor, can indicate an unacceptable risk for the patient's participation in the study.