Combination treatment for advanced HER2-positive solid tumors

A Phase I, Open-label, Dose Escalation Clinical Trial to Assess the Safety, Efficacy, Tolerability and Pharmacokinetics of the Recombinant Humanized Anti-PD1 Monoclonal Antiody (JS001) in Combination With Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate (RC48-ADC) in Treatment of HER2-Positive Advanced Malignant Solid Tumors

This study is testing a new combination treatment for people with advanced HER2-positive solid tumors to see if it is safe and effective.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Peking University (other)
• Drugs / interventions: radiation, prednisone
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT04280341 on ClinicalTrials.gov

What this trial studies

This Phase I clinical trial evaluates the safety, efficacy, tolerability, and pharmacokinetics of RC48-ADC in combination with the anti-PD1 monoclonal antibody JS001 for patients with HER2-positive advanced malignant solid tumors. The study consists of two parts: a dose escalation phase using a 3+3 design to determine the maximum tolerated dose (MTD) and a dose extension phase based on the results from the escalation. Patients will be enrolled sequentially at escalating doses to assess the treatment's effectiveness and safety profile.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced HER2-positive malignant solid tumors that are refractory to standard treatments.

Not a fit: Patients with HER2-negative tumors or those who have not progressed on standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced HER2-positive solid tumors who have limited treatment alternatives.

How similar studies have performed: Other studies have shown promising results with similar combinations of targeted therapies and immunotherapies in HER2-positive cancers, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Willing to sign the informed consent form;
* ≥18 years old;
* Diagnosed histologically or cytologically with local advanced or metastatic HER2-positive malignant solid cancer( indicating that IHC result is 2+,3+or1+ ) and under one of following situations: standard treatment-refractory (disease progression or no response), treatment-resistant, unable to receive treatment, or the standard treatment is unavailable;
* Having measurable or evaluable lesions according to RECIST 1.1;
* Having an ECOG performance status score of 0 or 1;
* Echocardiographic LVEF (left ventricular ejection fraction) ≥ 50%.
* NYHA CLAS 0-1;
* Having sufficient bone marrow, liver and kidney functions (based on the normal value of the clinical trial site) within 7 days before erollment: Absolute neutrophil count (ANC) ≥ 1.5×109/L,Platelets ≥ 100×109/L, hemoglobin≥ 9.0 g/dL；Total serum bilirubin ≤ 1.5×upper limit of normal (ULN);Without liver metastasis, ALT, AST or ALP ≤ 2.5×ULN; With liver metastasis, ALT, AST or ALP ≤ 5×ULN;Serum creatinine clearance rate ≥ 60 mL/min(Cockcroft-Gault formula);INR International Normalized Ratio ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN;
* With an expected survival of more than 3 months;
* Male or female patients of childbearing potential must agree to use effective methods of contraception (such as double-barrier contraceptive methods, condoms, oral or injectable contraceptives and intrauterine devices) during the study period and within 24 weeks after the last dosing;

Exclusion Criteria:

* Known active uncontrolled or symptomatic CNS metastases, as indicated by clinical symptoms, cerebral edema, spinal cord compression, carcinomatous meningitis, leptomeningeal disease and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated and are clinically stable o before the first dose of RC48-ADC.
* Prior treatment with HER2 targeted therapy while LVEF decline \<45% or absolute value of LVEF decline \>15%；
* Participation in any other studies within 4 weeks before study entry and/or during participation in the active treatment phase of the trial.
* Radical operation within 3 weeks before study entry but not include diagnostic puncture or peripheral vascular assess replacement ;
* Radical radiation therapy within 3 months before study entry; Patient of Palliative radiotherapy is eligible into this study if \<30 % Radiation area of bone marrow;
* Patients who underwent checkpoint inhibitor or tumor vaccines include not limited PD-1、 PD-1、PD-L1、CTLA4、LAG3;
* Patient has had systemic steroid therapy (≥10 mg/day of prednisone or physiologic replacement doses of hydrocortisone, or its equivalent) or immunosuppressive medication within 14 days prior to the first dose of study.
* Live vaccines within 28 days prior to the first dose of study and during trial treatment.
* Patient has an active autoimmune disease or a documented history of autoimmune disease (but not limited In terstitial lung Disease, uveitis, SLE, etal). Patients with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Patients that require inhaled steroids or local steroid injections would not be excluded from the study. Patients with vitiligo or psoriasis that is stable on hormone replacement will not be excluded from the study.
* Active and clinically significant bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
* Patients have uncontrollable systemic disease which including diabetes, hypertendion, pulmonary fibrosis, etal.
* The toxicity of previous anti-cancer therapy has not returned to 0 or 1 level as specified in CTCAE v4.0 (except for hair loss);
* Patient has a history of allogeneic HSCT or organ transplation before study entry;
* Patients with hypersensitivity or delayed hypersensitivity reactions to certain components of RC48-ADC or similar drugs;
* Patients with symptomatic include but not limited ascites or pleural effusion and mental disease.

Where this trial is running

Beijing, Beijing

• Beijing Cancer Hospital — Beijing, Beijing, China (RECRUITING)

Study contacts

• Principal investigator: Lin Shen, professor — Peking University
• Study coordinator: lin Shen, professor

Conditions: HER2-Positive Solid Tumors, RC48-ADC, JS001, HER2 positive solid Tumor