Clinical trial NCT06336148: A Phase 1a/1b Study of ACTM-838 in Patients With Advanced Solid Tumors
Official title: A Phase 1a/1b Open-label, Dose-Escalation and Expansion Study of ACTM-838 as a Single Agent in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Keywords: non-small cell lung cancer
head and neck cancer
esophageal cancer
ovarian cancer
cervical cancer
stomach cancer
thyroid cancer
renal cell cancer
mesothelioma
breast cancer
pancreatic cancer
colorectal cancer
sarcoma
immunotherapy
melanoma
bladder cancer
cholangiocarcinoma
bile duct cancer
Lead sponsor: Actym Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-03-28
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an Open label Single dose study.
Primary purpose: TREATMENT

Brief summary: This is a first in human (FIH) 2-part study using ACTM-838 in patients with advanced solid tumors resistant to standard of care treatment. Part 1a will evaluate dose escalation and Part 1b will evaluate dose expansion.

Detailed description: This study has 2 parts. Part 1a will evaluate the safety and tolerability and activity of escalating doses of ACTM-838 to estimate the maximum tolerated dose (MTD) and/or the optimum biological dose (OBD) for ACTM-838 as a monotherapy and determine the dose recommended for Part 1b.

Part 1b will further evaluate ACTM-838 in patients with advanced specific tumor types (defined pathologically, clinically and/or molecularly) based on data emerging from the Phase 1a and the pre-clinical program. The details on the Phase 1b dose expansion part will be incorporated in a future protocol amendment.

Eligibility criteria: Inclusion Criteria:

1. Advanced solid tumor for which there is no remaining standard curative therapy and no therapy with a demonstrated survival benefit, or they must be ineligible to receive or refuse to receive such therapy
2. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST ) v1.1; amenable for biopsy, and radiographically apparent on computed tomography (CT) or magnetic resonance imaging (MRI )
3. Eastern Cooperative Oncology Group (ECOG) 0-1
4. Adequate hematologic, hepatic, pulmonary, and cardiac function
5. CD4 count \>500/mL at screening
6. Additional protocol defined inclusion criteria may apply

Exclusion Criteria:

1. Active autoimmune disease requiring systemic treatment (i.e., with use of disease modifying agents, systemic corticosteroids or immunosuppressive drug) within the past 6 months prior to dosing of investigational product.
2. History of permanent artificial implants (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopaedic screw\[s\], metal plate\[s\], bone graft\[s\], or other exogenous implant\[s\]
3. Known history of cholelithiasis or urolithiasis
4. History of valvular disease, arterial aneurisms or arterial or venous malformation
5. Known active brain metastases
6. Documented active Salmonella infection or vaccination with Salmonella typhi within 6 months prior to investigational product dosing
7. Additional protocol defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Incidence and severity of adverse events and serious adverse events - Part 1a
timeFrame: 1 year
measure: Proportion of participants experiencing dose limiting toxicities - Part 1a
timeFrame: 28 Days
Secondary outcomes:
measure: Objective response rate (ORR) defined as complete response (CR) or partial response (PR) - Part 1a
timeFrame: 1 year
measure: Confirmed ORR defined as confirmed CR or confirmed PR - Part 1a
timeFrame: 1 year
measure: Clinical Benefit Rate (CR, PR, or stable disease (SD) as best overall response) - Part 1a
timeFrame: 1 year
measure: Duration of Response (DoR), defined as the time from date of first response (CR or PR) - Part 1a
timeFrame: 1 year
measure: Progression free survival (PFS) - Part 1a
timeFrame: 1 year
measure: Change in tumor markers - Part 1a
timeFrame: 1 year
measure: Amount of ACTM-838 in blood, urine, and faeces as measured by digital droplet-polymerase chain reaction (ddPCR) - Part 1a
timeFrame: 1 year
measure: Tumor PD colonization as measured by ddPCR and payload delivery as measured by RNA detection - Part 1a
timeFrame: 1 year
measure: Incidence of antidrug antibodies (ADA) to ACTM-838 - Part 1a
timeFrame: 1 year
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California Norris Comprehensive Cancer Center, 1441 Eastlake Ave.
state: California
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center, 5115 Centre Ave
state: Pennsylvania
city: Westmead
country: Australia
facility: Westmead Hospital, Cnr Hawkesbury Road and Darcy Road, Site No: 200
state: New South Wales
city: Bedford Park
country: Australia
facility: Southern Oncology Clinical Research Unit, Level 3, Mark Oliphant Building, 5 Laffer Drive, Site No: 202
state: South Australia
city: Melbourne
country: Australia
facility: Alfred Hospital, 55 Commercial Road, Site No: 201
state: Victoria
Study officials:
References: