A Study of RC118 Plus Toripalimab / RC148 in Patients with Locally Advanced Unresectable or Metastatic Solid Tumors

Inclusion Criteria:

1. Be able to participate in the study voluntarily and willing to provide writteninformed consent.

2. male or female 18 ≤ age ≤ 75 years old.

3. Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

4. The expected survival ≥12 weeks.

5. Enrollment of subjects with locally advanced or metastatic gastricadenocarcinoma/adenocarcinoma of the gastroesophageal junction who have ahistologically confirmed diagnosis and have failed standard therapy.

6. Subjects who received ≤2 prior systemic therapies.

7. Subjects agree to provide tumor tissue specimens for Claudin 18.2 and PD-L1expression levels during the screening period. Samples should have moderate to highexpression of Claudin 18.2 by membrane staining.

8. According to the RECIST v1.1, there is at least one measurable target lesion.

9. Sufficient heart, bone marrow, liver and kidney functions.

10. Fertile male or female subjects must agree to take effective contraceptive measuresduring the study period and for 6 months after the end of the last dose, such asdouble-barrier contraceptive methods(eg. condoms), oral or injectablecontraceptives, intrauterine.

Exclusion Criteria:

1. Pregnant women, breastfeeding women or women with a positive blood pregnancy testresult during the screening period (non-fertile women do not need to undergo apregnancy test, such as women with a previous hysterectomy and/or bilateraloophorectomy or amenorrhea ≥12 months).

2. Subjects with active hepatitis B (HBsAg positivity and HBV DNA titre higher than thenormal upper limit), active hepatitis C (HCVAb positivity and HCV RNA titre higherthan the normal upper limit), and positive human immunodeficiency virus antibody (HIV-Ab) results during the screening period.

3. Subjects with a history of other acquired or congenital immunodeficiency diseases,or who have undergone organ or bone marrow transplantation.

4. Subjects who have previously received monoclonal antibody, double antibody targetingdrugs, ADC, CAR-T and other therapeutic drugs targeting Claudin 18.2 or other ADCswith MMAE payload; or have participated in clinical trials and receivedinvestigational drugs within 4 weeks before the first dose.

5. Have vaccinated within 4 weeks prior to the first dose or plan to receive any livevaccine during the study.

6. Subjects are atallergic to the ingredients or excipients of the experimental drug.

7. Subjects who have received anti-tumor therapy (chemotherapy, radiotherapy,immunotherapy, or targeted therapy) within 4 weeks or less than 5 half-lives of theexperimental drug prior to the start of the first dose; or who have receivedanti-tumor therapy with traditional Chinese medicine or immunomodulators within 2weeks prior to the start of the first dose.

8. The toxicity of previous anti-tumor therapy has not returned to the level 0 or 1 asdefined by NCI-CTCAE v5.0 (except for alopecia, pigmentation and other long-termtoxicity ≤2 that cannot be recovered which was defined by investigators).

9. The clinical symptoms of pleural effusion, abdominal effusion, or pericardialeffusion that requires drainage.

10. Active infection within 2 weeks prior to the first dose that requires systemicanti-inflammatory therapy.

11. Complicating other diseases that seriously endanger the safety of the subjects oraffect the completion of the study, such as peptic ulcer, intestinal obstruction,intestinal paralysis, interstitial pneumonia, pulmonary fibrosis, renal failure anduncontrolled diabetes (Fasting blood glucose > 8.5 mmol/L, HbA1C ≥7.5%).

12. The tumor lesion has a bleeding tendency or has received blood transfusion treatmentwithin 4 weeks prior to the first dose.

13. During the screening period, QTc interval >450 ms(male), QTc interval >470ms(female); previous family or personal history of long/short QT intervalsyndrome; A history of ventricular arrhythmia deemed clinically significant by theinvestigator, or currently receiving antiarrhythmic medication, or implantation ofarrhythmia defibrillation device.

14. Previous myocardial infarction (within 6 months prior to the first dose), severe orunstable angina, coronary or peripheral artery bypass grafting, heart failure grade 3~4 defined by New York Heart Association (NYHA) and uncontrolled hypertension.

15. Experienced an arterial/venous thromboembolic event within 6 months prior to thestudy.

16. Active autoimmune disease that requires systemic treatment within 2 years prior tothe study. Patients with vitiligo, psoriasis, alopecia or Grave's disease that notrequires systemic treatment, hypothyroidism that only requires thyroid hormonereplacement therapy, and type 1 diabetes only requires insulin replacement therapymay be included in the study.

17. Subjects with brain metastases and/or carcinomatous meningitis who have previouslyreceived related treatment may be considered for inclusion if their disease has beenstable for at least 3 months, no imaging evidence of disease progression has beenobserved within 4 weeks prior to the first dose, all neurological symptoms havereturned to baseline, and radiation, surgery, or steroid therapy has beendiscontinued at least 28 days prior to the first dose; cancerous meningitis shouldbe excluded regardless of whether it is clinically stable.

18. Other malignant tumor within 5 years prior to the signature of informed consent.

19. Major surgery or interventional therapy was performed within 4 weeks prior to thefirst dose and did not fully recovered (except tumor biopsy and puncture).

20. For Phase II subjects:

• Received an immune checkpoint inhibitor (anti-PD-1/PD-L1/CTLA-4 antibody) orother immune checkpoint inhibitor therapy within 28 days prior to the firsttreatment with the test drug;

• Prior concurrent receipt of antitumor agents targeting VEGF/VEGFR andPD-1/PD-L1;

• Experienced permanent discontinuation of immunotherapy due to toxicity ofimmune checkpoint inhibitor therapy prior to receiving administration of studydrug;

• Currently receiving anticoagulant medications (except for subjects onprophylactic doses of heparin).

21. A history of uncontrollable mental illness or subjects currently experiencing suchconditions.

22. Subjects with poor compliance who are expected to be unable to complete the study.