Study Evaluating ISM8207 in Participants With Advanced Solid Tumors and Relapsed/Refractory B-Cell Lymphoma

A Phase 1, Open-label, Multicenter, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ISM8207 Monotherapy in Patients With Advanced Solid Tumors or Relapsed/Refractory B-Lymphoid Malignancies

The goal of this clinical trial is to study ISM8207 in participants with advanced solid tumors and relapsed/refractory B-cell lymphoma. The primary objective is to evaluate the safety and tolerability of ISM8207 orally administered in participants with advanced solid tumors and relapsed/refractory B-cell lymphoma

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors; Relapsed/Refractory B-cell Lymphoma
• Intervention / Treatment: Drug: ISM8207

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yichen Liu; Phone Number: 021-50831718; Email: Insilico-Clinicaltrial@insilico.ai
• Study Contact Backup: Name: Juan Xu; Email: Insilico-Clinicaltrial@insilico.ai

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Shanghai Jiao Tong University School of Medicine-Ruijin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female participants with age ≥18 years at the time of signing the informed consent.

2. Advanced solid tumors: Histologically confirmed advanced or metastatic solid tumors who have disease progression after standard therapy, intolerable to standard therapy, or for whom no standard therapy exists.

   B-cell lymphoma: Histologically confirmed B-cell lymphoma who had received at least one prior line of standard therapy and were relapsed after or refractory to the standard therapy.

3. Have measurable or evaluable lesions in Part 1 and at least one measurable target lesion in Part 2 as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria or Lugano 2014.
4. ECOG PS (Eastern Cooperative Oncology Group Performance Status)≤1.
5. Life expectancy of ≥12 weeks as judged by the investigator.
6. Adequate organ function as determined by medical assessment.
7. Capable of providing signed ICF and complying with the requirements and restrictions listed in the ICF and in this study protocol.
8. Female subjects of childbearing potential and male subjects must agree to use an effective method of contraception during the treatment period and for 90 days after the last dose of ISM8207.

Exclusion Criteria:

1. Prior treated with other QPCTL, CD47 or SIRPα inhibitors.
2. Burkitt lymphoma/leukemia, plasma cell myeloma, plasmablastic lymphoma.
3. Participation in other therapeutic clinical studies within 28 days or 5 half- lives (whichever is shorter) prior to first dose of study treatment.
4. Anti-tumor therapy (chemotherapy, immunotherapy, targeted therapy, biologic therapy, or other anti-tumor therapy) within 28 days or 5 half-lives, whichever is shorter prior to first dose of study treatment.
5. Previous allogeneic stem cell transplantation or autologous stem cell. transplantation within 3 months prior to first receiving study treatment.
6. Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding alopecia).
7. Received antitumor steroid therapy within 7 days prior to the first study treatment administration.
8. A serious illness or medical condition(s)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation: ISM8207; Participants will receive ISM8207 orally once on day 1 during single dose period (3 days) then once daily in repeated 28-day cycles from Cycle 1 onwards.	Drug: ISM8207; Pharmaceutical formulation: Capsules Mode of Administration: Oral
Experimental: Dose Expansion: ISM8207; Participants will receive ISM8207 orally once daily in repeated 28-day cycles.	Drug: ISM8207; Pharmaceutical formulation: Capsules Mode of Administration: Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of dose-limiting toxicity (DLT) events	31 days
Incidence and severity of adverse events (AEs)	Approximately 2 years
Recommended phase 2 dose (RP2D)	31 days

Secondary Outcome Measures

Outcome Measure	Time Frame
objective response rate (ORR)	Approximately 2 years
best objective response (BOR)	Approximately 2 years
duration of response (DoR)	Approximately 2 years
disease control rate (DCR)	Approximately 2 years
progression-free survival (PFS)	Approximately 2 years
6-month overall survival (OS) rates	Approximately 2 years
1-year overall survival (OS) rates	Approximately 2 years
maximum observed concentration (Cmax)	Approximately 2 years
time of maximum observed concentration (Tmax)	Approximately 2 years
area under the concentration-time curve (AUC)	Approximately 2 years
terminal half-life (t1/2)	Approximately 2 years
apparent clearance (CL/F)	Approximately 2 years
apparent volume of distribution (Vz/F)	Approximately 2 years
maximum observed concentration at steady state (Css,max)	Approximately 2 years
minimum observed concentration at steady state (Css,min)	Approximately 2 years
average concentration at steady state (Css,av)	Approximately 2 years
time of Css,max (Tss,max)	Approximately 2 years
AUC from time 0 to time dosing interval (AUCss,0-tau)	Approximately 2 years
CLss/Fss	Approximately 2 years
Vz/Fss	Approximately 2 years
accumulation ratio of Cmax (RCmax) after multiple doses	Approximately 2 years
accumulation ratio of AUC (RAUC) after multiple doses	Approximately 2 years

Collaborators and Investigators

• Sponsor: InSilico Medicine Hong Kong Limited

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2024
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: May 31, 2024
• First Submitted That Met QC Criteria: May 31, 2024
• First Posted (Actual): June 6, 2024

Study Record Updates

• Last Update Posted (Actual): June 7, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Advanced solid tumors; Lymphoma, B-cell; Relapsed/refractory B-cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: ISM8207_101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No