A Study to Evaluate the Safety, Tolerability, PK, PD, and Preliminary Efficacy of CS01 in Patients With Locally Advanced or Metastatic Solid Tumors

NCT07461181 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: AF0406/15.0/2024-09-12
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of CS01 in patients with locally advanced or metastatic solid tumors.

Conditions

Locally Advanced or Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Phase I: Incidence of DLT events during the observation period

  From the day of the first dose of treatment to 28 days after the first dose of treatment, up to 28 days.

• Phase I: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

  Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (based on CTCAE v5.0), treatment interruptions and dose adjustments due to toxicity; changes from baseline in physical examinations, ECOG performance status, laboratory tests, electrocardiograms (ECG), and vital signs.

  Through study completion, an average of 2 year

• Phase I: Recommended Phase II Dose (RP2D) for CS01 injection monotherapy

  Through study completion, an average of 2 year

• Phase II: Preliminary antitumor activity endpoint: Objective Response Rate (ORR)

  Preliminary antitumor activity endpoint: Objective Response Rate (ORR), defined as the proportion of subjects achieving a complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST v1.1.

  Through study completion, an average of 2 year

Secondary Outcomes (12)

• Phase I: Pharmacokinetics (PK): Cmax

  Through study completion, an average of 2 year

• Phase I: Pharmacokinetics (PK): elimination half-life (t½)

  Through study completion, an average of 2 year

• Phase I: Pharmacodynamics (PD): OX40 receptor occupancy.

  5 weeks

• Phase I: Immunogenicity: percentage of subjects positive for ADA

  Through study completion, an average of 2 years

• Phase I: Preliminary antitumor activity endpoint: ORR

  Through study completion, an average of 2 year

Study Arms (4)

0.03 mg/kg CS01

EXPERIMENTAL

This phase will utilize an accelerated titration design (for the first dose group only) and a "3+3" design. It will enroll approximately 10 patients with locally advanced or metastatic solid tumors who have failed standard treatment, are intolerant, or lack effective treatment options. The four planned dose groups are: 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, and 1 mg/kg. All patients will receive CS01 injection via intravenous infusion once every two weeks (Q2W), with every 4 weeks constituting one treatment cycle. Dose-Limiting Toxicity (DLT) assessments will be conducted at the end of the 4th week for each dose group. Antitumor efficacy assessments (based on RECIST v1.1 criteria) will be performed every 8 weeks. Safety data will be collected throughout the treatment period, and blood samples for PK, PD, immunogenicity, and biomarker analyses will also be collected.

Biological: CS01 (an anti-OX40 antibody)

0.1 mg/kg CS01

EXPERIMENTAL

This phase will utilize an accelerated titration design (for the first dose group only) and a "3+3" design. It will enroll approximately 10 patients with locally advanced or metastatic solid tumors who have failed standard treatment, are intolerant, or lack effective treatment options. The four planned dose groups are: 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, and 1 mg/kg. All patients will receive CS01 injection via intravenous infusion once every two weeks (Q2W), with every 4 weeks constituting one treatment cycle. Dose-Limiting Toxicity (DLT) assessments will be conducted at the end of the 4th week for each dose group. Antitumor efficacy assessments (based on RECIST v1.1 criteria) will be performed every 8 weeks. Safety data will be collected throughout the treatment period, and blood samples for PK, PD, immunogenicity, and biomarker analyses will also be collected.

Biological: CS01 (an anti-OX40 antibody)

0.3 mg/kg CS01

EXPERIMENTAL

This phase will utilize an accelerated titration design (for the first dose group only) and a "3+3" design. It will enroll approximately 10 patients with locally advanced or metastatic solid tumors who have failed standard treatment, are intolerant, or lack effective treatment options. The four planned dose groups are: 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, and 1 mg/kg. All patients will receive CS01 injection via intravenous infusion once every two weeks (Q2W), with every 4 weeks constituting one treatment cycle. Dose-Limiting Toxicity (DLT) assessments will be conducted at the end of the 4th week for each dose group. Antitumor efficacy assessments (based on RECIST v1.1 criteria) will be performed every 8 weeks. Safety data will be collected throughout the treatment period, and blood samples for PK, PD, immunogenicity, and biomarker analyses will also be collected.

Biological: CS01 (an anti-OX40 antibody)

1 mg/kg CS01

EXPERIMENTAL

This phase will utilize an accelerated titration design (for the first dose group only) and a "3+3" design. It will enroll approximately 10 patients with locally advanced or metastatic solid tumors who have failed standard treatment, are intolerant, or lack effective treatment options. The four planned dose groups are: 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, and 1 mg/kg. All patients will receive CS01 injection via intravenous infusion once every two weeks (Q2W), with every 4 weeks constituting one treatment cycle. Dose-Limiting Toxicity (DLT) assessments will be conducted at the end of the 4th week for each dose group. Antitumor efficacy assessments (based on RECIST v1.1 criteria) will be performed every 8 weeks. Safety data will be collected throughout the treatment period, and blood samples for PK, PD, immunogenicity, and biomarker analyses will also be collected.

Biological: CS01 (an anti-OX40 antibody)

Interventions

CS01 (an anti-OX40 antibody) BIOLOGICAL

OX40 is a costimulatory receptor expressed on activated CD4⁺ and CD8⁺ T cells that enhances T-cell proliferation and survival within the tumor microenvironment. CS01 is a novel agonistic anti-OX40 IgG monoclonal antibody optimized with an intermediate binding-affinity Fab and a constant domain enabling enhanced Fcγ receptor engagement.

0.03 mg/kg CS01; 0.1 mg/kg CS01; 0.3 mg/kg CS01; 1 mg/kg CS01

Eligibility Criteria

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

You may qualify if:

• Subjects must meet ALL of the following criteria for enrollment:
• Age: 18 years or older (inclusive), male or female.
• ECOG Performance Status: 0 to 1.
• Disease Characteristics:
• Dose Escalation Phase: Subjects with histologically or cytologically confirmed unresectable or metastatic advanced solid tumors, who have failed standard treatment or are intolerant (disease progression, or intolerance to chemotherapy, targeted therapy, etc.), or who lack effective treatment options.
• Dose Expansion Phase: Tumor types for which ≥1 instance of partial response (PR), or tumor-shrinking stable disease (SD), or biomarkers suggesting potential clinical benefit are observed during the dose escalation phase, as decided by the Safety and Efficacy Data Assessment Committee.
• The subject must have at least one measurable lesion as defined by RECIST v1.1.
• Agreement to provide tumor tissue specimens (optional).
• o Note: For the dose escalation phase, tumor tissue samples equivalent to 4 FFPE unstained slides, or an equivalent amount of FFPE archived (within 2 years) or newly obtained tissue blocks are required. For the dose expansion phase, at least 4 and up to 9 FFPE unstained slides, or an equivalent amount of FFPE archived (within 2 years) or newly obtained tissue blocks are required. The FFPE biopsy must be from a surgical resection or core needle biopsy.
• Life expectancy ≥ 3 months.
• Recovery from toxicities of previous anti-tumor therapy to ≤ Grade 1 per CTCAE v5.0 (except for toxicities judged by the investigator to pose no safety risk, alopecia, or Grade 2 peripheral neuropathy judged irreversible). Immune-related adverse reactions must have completely resolved to baseline or Grade 1.
• Normal function of major organs, meeting the following laboratory criteria:
• AST and ALT ≤ 2.5 × ULN; for subjects with liver metastases, AST and ALT ≤ 5 × ULN.
• Total Bilirubin (TBil) ≤ 1.5 × ULN; for subjects with liver metastases or confirmed/suspected Gilbert's syndrome, TBil ≤ 3 × ULN.
• Absolute Neutrophil Count (ANC) ≥ 1.5 × 10\^9/L.

You may not qualify if:

• Subjects who meet ANY of the following criteria will be excluded from the study:
• Previous treatment with anti-TNFR agonistic drugs.
• Active autoimmune disease requiring systemic treatment within 12 months prior to the initiation of study treatment. This includes, but is not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, granulomatosis with polyangiitis (Wegener's granulomatosis), Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Exceptions are made for the following:
• Subjects with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone therapy are eligible.
• Subjects with type 1 diabetes mellitus controlled on an insulin regimen are eligible.
• Subjects with eczema, psoriasis, chronic lichen simplex, or vitiligo with dermatologic manifestations only (e.g., subjects with psoriatic arthritis are excluded) may be enrolled if they meet ALL of the following conditions:
• i. The subject's rash covers \<10% of body surface area. ii. The disease is well controlled at baseline, requiring only low-potency topical corticosteroids.
• iii. There has been no acute exacerbation of the underlying condition within the past 12 months, or any acute exacerbation did not require treatment with psoralen plus ultraviolet A (PUVA) therapy, methotrexate, retinoids, biologics, oral calcineurin inhibitors, or high-potency/oral corticosteroids.
• Subjects with a history of two or more primary synchronous or metachronous malignancies are excluded, except for cured carcinoma in situ or basal cell carcinoma. Other malignancies that have been stably treated for over 5 years prior to enrollment are allowed.
• Within 4 weeks prior to the initiation of study treatment, subjects who have received the following treatments or medications:
• Participation in another clinical trial involving an investigational drug (including investigational vaccines) or invasive investigational medical device, or current enrollment in an interventional investigational study.
• Systemic anti-tumor therapy within 2 weeks prior to treatment initiation, or screening occurs within 5 half-lives of the previously administered drug (whichever is shorter).
• Major surgery or significant trauma, or being in the recovery period which, in the investigator's judgment, may affect the trial, or having a planned surgery during the study period.
• Chest radiotherapy or extensive field radiotherapy (defined as irradiation of \>50% of pelvic bone marrow or equivalent) within 4 weeks, or palliative radiotherapy within 2 weeks prior to treatment initiation.
• Administration of a live attenuated vaccine within 4 weeks prior to the first dose of study treatment, or expectation of requiring such a vaccine during the study or within 5 months after the last dose of study treatment.

Sponsors & Collaborators

• Ruijin Hospital: lead
• Zhongshan Constimulus Bio Co., Ltd: collaborator

Study Sites (1)

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2026
• First Posted: March 10, 2026
• Study Start: December 30, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 10, 2026

Record last verified: 2026-01

Locations

CN (1)