A Phase 1a/​1b Study of ACTM-838 in Patients With Advanced Solid Tumors

Primary Outcome Measures

• Incidence and severity of adverse events and serious adverse events – Part 1a and Part 1b
• Proportion of participants experiencing dose limiting toxicities – Part 1a and 1b
• Objective response rate (ORR) as defined as complete response (CR) or partial response (PR) – Part 1a and Part 1b
• Confirmed ORR defined as confirmed CR or confirmed PR – Part 1b
• Clinical Benefit Rate (CR, PR, or stable disease (SD) as best overall response) – Part 1b
• Duration of Response (DoR), defined as the time from date of first response (CR or PR) – Part 1b
• Progression free survival (PFS) – Part 1b
• Change in tumor markers – Part 1b
• Amount of ACTM-838 in blood, urine, and faeces as measured by digital droplet-polymerase chain reaction (ddPCR) – Part 1b

Secondary Outcome Measures

• Objective response rate (ORR) defined as complete response (CR) or partial response (PR) – Part 1a
• Confirmed ORR defined as confirmed CR or confirmed PR – Part 1a
• Clinical Benefit Rate (CR, PR, or stable disease (SD) as best overall response) – Part 1a
• Duration of Response (DoR), defined as the time from date of first response (CR or PR) – Part 1a
• Progression free survival (PFS) – Part 1a
• Change in tumor markers – Part 1a
• Amount of ACTM-838 in blood, urine, and faeces as measured by digital droplet-polymerase chain reaction (ddPCR) – Part 1a
• Tumor PD colonization as measured by ddPCR and payload delivery as measured by RNA detection – Part 1a

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, and cardiac function
5. CD4 count >500/mL at screening

Exclusion Criteria

1. Current use of nonsteroidal anti-inflammatory drugs or COX-2 inhibitors
2. Active autoimmune disease requiring systemic treatment (i.e., with use of disease modifying agents, systemic corticosteroids or immunosuppressive drug) within the past 2 years prior to dosing of investigational product.
3. 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]
4. History of cholelithiasis or urolithiasis
5. History of valvular disease, arterial aneurisms or arterial or venous malformation
6. Known brain metastases
7. Documented active Salmonella infection or vaccination with Salmonella typhi within 6 months prior to investigational product dosing
8. Additional protocol defined inclusion/exclusion criteria may apply