IPG7236 Combined With Toripalimab in Participants With Advanced Solid Tumors

A Phase I/II Multicenter, Non-randomized, Open-label, Dose Escalation and Expansion Study of IPG7236 Combined With Toripalimab Treatment of Advanced Solid Tumors in Adult Patients to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity

Phase 1/2 Study for IPG7236 Combined With Toripalimab in Participants With Advanced Solid Tumors

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: IPG7236; Drug: Toripalimab Injection

Detailed Description

This is a phase 1/2, multicenter, non-randomized, open-label, dose-escalation and dose-expansion study. Part A (dose escalation) will adopt a standard "3+3" design with two cohorts (IPG7236 500 mg BID + Toripalimab 240 mg Q3W; IPG7236 800 mg BID + Toripalimab 240 mg Q3W) to determine the MTD and/or RP2D. Part B (dose expansion) will enroll approximately 40 CCR8-positive advanced solid tumor patients to further evaluate safety,tolerability and preliminary antitumor activity. The transition from Part A to Part B will be triggered after confirmation of RP2D based on safety, tolerability, PK and preliminary efficacy data.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: jian fei wang, CSO; Phone Number: +86-21-34782827; Email: jfwang@immunophage.com.cn

Study Locations

• China
  • PuDongXinQu
    • Shanghai, PuDongXinQu, China, 200120
      • Shanghai Gaobo Tumor Hospital
      • Contact: Jin Li; Phone Number: +86-021-60571204; Email: lijin@csco.org.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Written informed consent must be obtained before any study procedure is performed.
2. Men or women 18 years of age or older.
3. Histologically or cytologically confirmed advanced or recurrent malignant solid tumors that are metastatic or unresectable. (Subjects must submit tumor tissue sections from within the past 5 years for CCR8 expression testing. For subjects without paraffin-embedded tissues, a fine-needle aspiration biopsy may be performed. Subjects who cannot provide tumor tissue sections or undergo biopsy are only eligible for inclusion during the dose escalation phase. During the dose expansion phase, CCR8 positivity must be known or tumor tissue sections must be provided with confirmed CCR8 expression.)
4. Subjects must have failed or been intolerant to standard antitumor therapy, or lack a standard treatment regimen, or be deemed by the investigator as currently unsuitable for standard therapy.
5. According to the RECIST 1.1 criteria, there is at least one measurable lesion.
6. Life expectancy ≥ 3 months.
7. Subjects must be able to swallow the oral investigational drug.
8. The ECOG performance status score is 0 or 1.

9. Sufficient hematologic and organ function, with the following laboratory test values:

   1. Hematology: Absolute Neutrophil Count (ANC) ≥ 1.5×10⁹/L; platelet count ≥ 75×10⁹/L; Hemoglobin ≥ 9 g/dL; lymphocytes ≥ 0.8×10⁹/L;
   2. Renal: Creatinine clearance calculated by the Cockcroft-Gault method ≥ 50 mL/min or serum creatinine ≤ 1.5× upper limit of normal (ULN);
   3. Hepatic: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3×ULN, or ≤ 5×ULN for subjects with liver metastases; total bilirubin ≤ 1.5×ULN, or ≤ 3×ULN for subjects with Gilbert syndrome or genetically equivalent conditions;
   4. Coagulation: Prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5× upper limit of normal (ULN).
10. Patients must be willing and able to comply with all scheduled visits, treatments, laboratory tests, and other study requirements.
11. Male and female participants of reproductive potential who engage in heterosexual sexual behavior must agree to use reliable contraceptive methods (hormonal, barrier, or abstinence,etc.) for at least 4 months during the trial period and after the last study drug administration (refer to Appendix 13.1 of the protocol)

Exclusion Criteria:

1. Primary malignant tumors of the central nervous system or malignant tumors associated with human immunodeficiency virus (HIV) .
2. Previous use of CCR8-targeted therapy.

3. Received the following treatment within the specified time frame:

   1. Planned major surgery within 4 weeks prior to the first dose administration (excluding minor procedures such as vascular access placement, gastrointestinal/biliary stent placement, or biopsy);
   2. Immunotherapy or biological therapy administered within 28 days prior to the initial administration;
   3. Chemotherapy <21 days prior to the first dose, or mitomycin or nitrosoureas < 42 days prior, or oral fluoropyrimidines < 14 days prior;
   4. Targeted small-molecule therapy or traditional Chinese medicine with antitumor indications administered within 14 days prior to the initial dose;
   5. Hormone therapy or other adjuvant therapies are not permitted if initiated within 14 days prior to the first dose. Exceptions: anti-estrogen therapy, bisphosphonates, RANKL monoclonal antibodies, somatostatin analogs, and leuprorelin are permitted if initiated ≥ 14 days prior to the first dose.
   6. Radiotherapy administered within 28 days prior to the first dose, or palliative radiotherapy within 14 days prior. Exception: Palliative radiotherapy (e.g., for analgesia) may be performed during the study drug administration period, provided that it is not permitted during the DLT observation period, any previously induced adverse events from radiotherapy have been resolved to grade <2, and the radiotherapy was not directed at the target lesion.
   7. Other investigational or treatments administered within 28 days prior to the first dose;
   8. Any previous allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation;
4. Previous treatment-related toxicity has not yet resolved to a level of ≤ 1 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v6.0 or to the specified levels in the inclusion/exclusion criteria (except for safety risks deemed by the investigator as not significant, such as alopecia, grade 2 peripheral neuropathy, hypothyroidism or hyperthyroidism, or other endocrine disorders well-controlled by hormone replacement therapy).
5. In combination with other active malignancies (excluding basal cell carcinoma of the skin, cervical carcinoma in situ, or superficial bladder cancer with no evidence of disease after potentially curative treatment; For other patients with previous malignant tumors who have survived without disease for more than 3 years, they are also (acceptable).
6. Immune-related adverse events (irAEs) of grade ≥ 3 or those leading to treatment discontinuation during prior immunotherapy, or grade ≥ 2 immune-mediated myocarditis, or treatment discontinuation due to allergic or infusion-related reactions.
7. Diagnosis of primary or acquired immunodeficiency, or receipt of systemic glucocorticoids or any other form of immunosuppressive therapy within 7 days prior to the first dose. Exceptions: intraocular, intranasal, intra-articular, inhaled, or systemic glucocorticoids (prednisone dose ≤ 10 mg/day or equivalent, or doses used for adrenal replacement therapy), as well as a single dose of immunosuppressive medication for contrast agent allergy prophylaxis (if no active autoimmune disease is present).
8. History of autoimmune disease requiring systemic therapy or active autoimmune diseases (i.e., requiring glucocorticoids or immunosuppressive agents for disease control) within 2 years prior to study initiation are eligible, provided they do not require immunosuppressive therapy for conditions such as type 1 diabetes mellitus, vitiligo, psoriasis,hypothyroidism, or hyperthyroidism.
9. Known severe or life-threatening allergic reactions to humanized monoclonal antibodies (mAbs) or intravenous immunoglobulin (Ig) preparations; known hypersensitivity to any investigational drug, its analogues, or excipients.
10. Untreated brain metastases, meningeal metastases, or spinal cord compression not definitively treated with surgery or radiotherapy. (Patients with brain metastases who have stabilized without symptoms after prior treatment and have not received high-dose steroid therapy are eligible for enrollment.)
11. Uncontrolled or requiring intravenous anti-infective therapy for active bacterial, fungal, or viral infections.

12. Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV) and/or HIV:

    1. Participants must be negative for hepatitis B surface antigen (HBsAg).
    2. For HCV antibody-positive subjects, the HCV RNA quantification must be below the research center's detection limit.
    3. HIV test must be negative at screening;
13. Administration of live or live-attenuated vaccines within 4 weeks prior to the first dose (inactivated vaccines, viral vector vaccines, and mRNA vaccines are permitted; seasonal vaccines should be completed prior to the first dose).
14. The serum pregnancy test is positive within 3 days before the first dose.
15. Lactating female subjects.
16. Pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis) requiring glucocorticoid therapy.
17. Patients with clinically uncontrollable ascites or pleural effusion are deemed unsuitable for enrollment by the investigator.
18. Symptomatic cardiovascular or cerebrovascular disease; accident/stroke or myocardial infarction (MI), unstable angina, congestive heart failure (NYHA class III or higher), or severe arrhythmias uncontrolled by pharmacotherapy within 6 months prior to enrollment; mean QT interval corrected for heart rate using the Fridericia formula (QTcF) ≥ 470 ms.
19. Any medical or social condition that may expose subjects to higher risks, affect compliance, or obscure the interpretation of safety or other clinical study data

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A（Cohort 1） ：IPG7236 500mg & Toripalimab; 3-6 subjects in this cohort will receive IPG7236 500 mg BID and Toripalimab Injection 240 mg， Dose-escalation cohort with 3+3 design; DLT assessment period is 21 days.	Drug: IPG7236; IPG7236: Part A: 500 mg BID or 800 mg BID, the dose in Part B is the RP2D confirmed in Part A, Oral (fasting: 1 hour before meal or 2 hours after meal, every 12±2 hours), Continuous daily administration, 21-day treatment cycle,Until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons for withdrawal; Drug: Toripalimab Injection; Toripalimab Injection: 240 mg , Q3W, 21-day treatment cycle, the first infusion lasts at least 60 minutes; if well tolerated, subsequent infusions can be shortened to 30 minutes.
Experimental: Part A（Cohort 2）：IPG7236 800mg& Toripalimab; 3-6 subjects in this cohort will receive IPG7236 800 mg BID and Toripalimab Injection 240 mg，Dose-escalation cohort with 3+3 design; enrolled sequentially after Cohort 1; DLT assessment period is 21 days.	Drug: IPG7236; IPG7236: Part A: 500 mg BID or 800 mg BID, the dose in Part B is the RP2D confirmed in Part A, Oral (fasting: 1 hour before meal or 2 hours after meal, every 12±2 hours), Continuous daily administration, 21-day treatment cycle,Until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons for withdrawal; Drug: Toripalimab Injection; Toripalimab Injection: 240 mg , Q3W, 21-day treatment cycle, the first infusion lasts at least 60 minutes; if well tolerated, subsequent infusions can be shortened to 30 minutes.
Experimental: Part B：IPG7236 RP2D & Toripalimab; 40 subjects in this cohort will receive IPG7236 at the RP2D BID and Toripalimab Injection 240 mg	Drug: IPG7236; IPG7236: Part A: 500 mg BID or 800 mg BID, the dose in Part B is the RP2D confirmed in Part A, Oral (fasting: 1 hour before meal or 2 hours after meal, every 12±2 hours), Continuous daily administration, 21-day treatment cycle,Until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons for withdrawal; Drug: Toripalimab Injection; Toripalimab Injection: 240 mg , Q3W, 21-day treatment cycle, the first infusion lasts at least 60 minutes; if well tolerated, subsequent infusions can be shortened to 30 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose-Limiting Toxicity (DLT)	Dose-Limiting Toxicity (DLT) is treatment-related adverse events (excluding disease progression/external causes) per NCI CTCAE v6.0, occurring within Cycle 1 Day 1-21,1) Unexplained death; 2) Hematological: Grade 4 neutropenia >7d; Grade ≥3 febrile neutropenia; Grade 4 thrombocytopenia or Grade 3 with clinical bleeding; Grade 4 anemia; 3) Non-hematological: Grade ≥3 (exceptions: Grade 3 nausea/vomiting/diarrhea <3d with antiemetics; Grade 3 fatigue <1w; pancreatitis-unrelated Grade ≥3 amylase/lipase; Grade ≥3 electrolyte disturbance resolving within 72h without complications; asymptomatic isolated lab abnormalities); Hepatotoxicity: Hy's Law (ALT/AST >3×ULN + total bilirubin >2×ULN + ALP <2×ULN); AST/ALT >8×ULN (or >8×baseline for liver metastasis); AST/ALT >5×ULN (or >5×baseline for liver metastasis) ≥14d; Other Grade 4 non-hematological toxicity; 4) Toxicity requiring permanent study drug discontinuation or <75% planned administration. Infusion-related reactions are not DLT;	Up to 21 days after first dose (Cycle 1): To determine the DLT according to NCI CTCAE v6.0, and define the Maximum Tolerated Dose (MTD) and RP2D of IPG7236 in combination with toripalimab
Percentage of patients with adverse events		From first dose to 90 days after last dose or initiation of new anti-cancer therapy, whichever comes first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) per iRECIST v1.1	Objective Response Rate (ORR) is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) per iRECIST v1.1 criteria.	From first dose to disease progression or death (up to 24 months)
Disease Control Rate (DCR) per iRECIST v1.1	Disease Control Rate (DCR) is defined as the percentage of participants with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) per iRECIST v1.1 criteria.	From first dose to disease progression or death (up to 24 months)
Duration of Response (DoR) per iRECIST v1.1	Duration of Response (DoR) is defined as the time from first documentation of objective response (CR or PR) to first documentation of progressive disease (PD) or death due to any cause, per iRECIST v1.1 criteria.	From first documentation of objective response (CR or PR) to first documentation of progressive disease (PD) or death (up to 24 months)
Progression-Free Survival (PFS) per iRECIST v1.1	Progression-Free Survival (PFS) is defined as the time from first dose to first documentation of progressive disease (PD) per iRECIST v1.1 criteria or death due to any cause, whichever occurs first.	From first dose to disease progression or death (up to 24 months)
Overall Survival (OS) per iRECIST v1.1	Overall Survival (OS) is defined as the time from first dose to death due to any cause.	From first dose to death due to any cause (up to 24 months)
Peak Plasma Concentration (Cmax) of IPG7236	Peak plasma concentration of IPG7236, determined from plasma concentration-time profiles obtained at preset time points.	From first dose to end of treatment, assessed up to 24 months
Trough Plasma Concentration (Cmin) of IPG7236	Trough plasma concentration of IPG7236, determined from plasma concentration-time profiles obtained at preset time points.	From first dose to end of treatment, assessed up to 24 months
Area Under the Plasma Concentration-Time Curve (AUC) of IPG7236	Area under the plasma concentration-time curve of IPG7236, calculated using non-compartmental analysis from plasma samples collected at preset time points.	From first dose to end of treatment, assessed up to 24 months
Time to Peak Plasma Concentration (Tmax) of IPG7236	Time to reach peak plasma concentration of IPG7236, determined from plasma concentration-time profiles obtained at preset time points.	From first dose to end of treatment, assessed up to 24 months
Elimination Half-Life (T1/2) of IPG7236	Elimination half-life of IPG7236, calculated from the terminal phase of the plasma concentration-time curve obtained at preset time points.	From first dose to end of treatment, assessed up to 24 months

Collaborators and Investigators

• Sponsor: Nanjing Immunophage Biotech Co., Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): July 30, 2029

Study Registration Dates

• First Submitted: March 23, 2026
• First Submitted That Met QC Criteria: March 27, 2026
• First Posted (Actual): April 2, 2026

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: toripalimab
• Other Study ID Numbers: IPG7236-C003

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
• product manufactured in and exported from the U.S.: No