Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmocodynamics and Preliminary Antitumor Activity of AT-1965 in Patients With Advanced, Refractory or Recurrent Solid Tumors

NCT06234098 | Recruiting Phase 1 FDA Drug

• 1 other identifier: AT-1965-101
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Solid Tumor

Keywords

Advanced Solid Tumors; Refractory Solid Tumors; Recurrent Solid Tumors

Outcome Measures

Primary Outcomes (3)

• Dose Limiting Toxicity (DLT) according to CTCAE version 5.0 in Part A - Dose Escalation Phase

  Nature and frequency of dose-limiting toxicities (DLTs) associated with AT-1965 administration, maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D)

  Dose limiting toxicities will be evaluated during the first treatment cycle (28 days)

• Objective Response Rate (ORR) based on RECIST version 1.1 in Part B - Dose Expansion Phase

  Objective Response Rates (ORR) defined as proportion of patients with a best overall response of complete response (CR) or partial response (PR) according to RECISTv1.1 as assessed by the Investigator

  3, 6 and 9 month

• Duration of Response (DoR) based on RECIST version 1.1 in Part B - Dose Expansion Phase

  Duration of response (DoR) defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented according to RECIST v1.1 as assessed by the Investigator.

  3, 6 and 9 month

Secondary Outcomes (16)

• Area under the concentration-time curve from zero to a definite time [AUC(0-t)]

  Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)

• Area under the concentration-time curve from zero to 168 hours [AUC(0-168)]

  Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)

• Area under the concentration-time curve from zero to 24 hours

  Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)

• Area under the concentration-time curve from zero to an infinite time [AUC(0-inf)]

  Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)

• Maximum plasma concentration [Cmax]

  Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)

Study Arms (1)

AT-1965 Liposome Injection

EXPERIMENTAL

Drug: AT-1965 Liposome Injection

Interventions

AT-1965 Liposome Injection DRUG

AT-1965 Liposome Injection administered intravenously once weekly for the first 3 weeks (Days 1, 8 and 15) of a 4 week cycle.

AT-1965 Liposome Injection

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• 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.
• The patient has an ECOG performance status of 0 to 2.
• The patient has adequate bone marrow, renal, and hepatic function, defined as follows:
• Hemoglobin ≥9.5 g/dL (without transfusion in the prior 3 weeks).
• Platelets ≥100 × 109 cells/L (may be achieved with transfusion as per PI discretion)
• ANC ≥1.5 ×109 cells/L (without the use of hematopoietic growth factors within 4 weeks prior to dosing).
• Creatinine Clearance ≥60 mL/min (by using Cockcroft-gault equation)
• Total bilirubin ≤1.5 × ULN, unless the patient has a prior history of Gilbert's syndrome, in which case ≤3.0 × ULN is acceptable.
• AST and ALT ≤2.5 × ULN; or ≤5 × ULN if due to liver involvement by tumor
• 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.
• 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:
• Hormonal contraceptives (e.g., birth control pills, skin patches, vaginal rings, or the Depo-Provera® shot)
• Intrauterine device (IUD)

You may not qualify if:

• 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.
• 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.
• Uncontrolled diabetes.
• Patients with a history of autoimmune disease. Excluded autoimmune conditions are listed in Appendix 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).
• 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.
• History of hemolysis or hemolytic anemia.
• Evidence of ongoing subclinical hemolysis (high LDH and low serum haptoglobin with increased reticulocyte count).
• History of adrenal gland disorders such as Cushing Syndrome, Congenital adrenal hyperplasia, Addison's Disease and hyperaldosteronism
• Recipient of an allogeneic bone marrow transplantation or solid organ transplantation.
• Endocrinopathy, unless on stable hormone replacement therapy.
• 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.
• Clinically significant cardiovascular disease including:
• Myocardial infarction or stroke within 6 months prior to the initiation of study treatment.
• LVEF \<50% on baseline assessment.

Sponsors & Collaborators

• Alyssum Therapeutics: lead
• CBCC Global Research: collaborator

Study Sites (7)

CBCC Global Research Site 001

Scottsdale, Arizona, 85258, United States

RECRUITING

CBCC Global Research Site 005

Bakersfield, California, 93309, United States

RECRUITING

CBCC Global Research Site 007

El Segundo, California, 90245, United States

RECRUITING

CBCC Global Research Site 008

Santa Monica, California, 90403, United States

RECRUITING

CBCC Global Research Site 003

Stanford, California, 94305, United States

RECRUITING

CBCC Global Research Site 002

Portland, Oregon, 97239, United States

RECRUITING

CBCC Global Research Site 006

Dallas, Texas, 75230, United States

RECRUITING

Study Officials

• Richard Fahrner, PhD

  Alyssum Therapeutics

  STUDY DIRECTOR

Central Study Contacts

Britney Barrera

CONTACT

661-376-0047; britney.barrera@cbcc.global

Eldho Jose

CONTACT

+91 9095326268; eldho.jose@cbcc.global

Study Design

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

Study Record Dates

• First Submitted: January 18, 2024
• First Posted: January 31, 2024
• Study Start: February 13, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: May 2, 2025

Record last verified: 2025-04

Locations

US (7)