Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Biliary Tract Cancer

All Drugs and Chemicals

Antibodies

Antibodies, Bispecific

Immunoglobulins

Immunologic Factors

6 mg/kg cardonilizumab, 14 days for 1 course.

1.8mg /mg LM-302 was treated for 1 course for 14 days.

6 mg/kg cardonilizumab for 14 days was a course of treatment; RP2D LM-302 is 1 course of treatment for 14 days

cardonilizumab:PD1 and CTLA-4 bispecific antibody

cardonilizumab

LM-302

Guo-Ming Shi, MD

Xiao-Yong Huang, MD

Jia Fan, MD

In this clinical study, we will evaluate the efficacy and safety of cardonilimumab (PD1 monoclonal antibody and CTLA-4 monoclonal antibody bisspecific antibodies) and LM-302 (Claudin18.2-ADC) in Claudin18.2-positive advanced BTC patients who have progressed after SOC and PD1/PD-L1 monoclonal antibody treatment.

The prognosis for unresectable and metastatic biliary malignancies (BTC) is extremely poor, with a median overall survival of only about 1 year for advanced biliary tumors treated with gemcitabine and cisplatin or combined with duvaliumab (PD-L1) as recommended by NCCN guidelines. At present, the NCCN guidelines recommend that the posterior line treatment of advanced BTC, such as FOLFOX, has a very limited effect, with an objective response rate of only about 5% and a median survival time of only about 6 months. There is an urgent need to develop new therapeutic methods to improve patient survival. Chronic inflammation caused by viral infection and bile duct stones are the most common potential risk factors for BTC, and immune system abnormalities play a key role in the occurrence and development of BTC. BTC, including intrahepatic cholangiocarcinoma (iCCA), showed abnormal expression of immune checkpoint molecules PD-L1 and CTLA-4 and obvious heterogeneity. Therefore, immunotherapy is of great value. TOPAZ-1 and KENOTE-966 studies both showed the value of PD-L1/PD1 monoclonal antibody in the treatment of advanced BTC. There is currently a lack of treatment options for progression after treatment with standard chemotherapy (SOC) combined with PD-L1/PD1 monoclonal antibodies. CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors have shown significantly enhanced clinical effects. Clinical studies on treating CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors have been carried out in several solid tumors. Although significant therapeutic effects have been achieved, adverse reactions (AEs) that cannot be ignored limit the benefit of patients. Claudin18.2 is a newly discovered tumor therapeutic target. Multiple clinical studies have shown that Claudin18.2 monoclonal antibody, Claudin18.2-ADC, and Cart-Claudin18.2 have good ORR in Claudin18.2-positive gastric cancer. At present, no independent research data on advanced BTC has been reported.

In this clinical study, we will evaluate the efficacy and safety of cardonilimumab (PD1 monoclonal antibody and CTLA-4 monoclonal antibody bispecific antibodies) and LM-302 (Claudin18.2-ADC) in Claudin18.2-positive advanced BTC patients who have progressed after SOC and PD1/PD-L1 monoclonal antibody treatment.

Each cycle of the first phase was defined as cardonilizumab (6mg/kg,Q2W) combined with different concentrations of 1.6mg/kg or 1.8mg/kg LM-302 (Q2W), 14 days as a course of treatment, and the combined dose (RP2D) of LM-302 during combination therapy was determined according to the 3+3 design.

In the second phase, Claudin18.2 expression was positive, and the positive population was randomly assigned to trial group 1, trial group 2, and trial group 3.

Group 1:6 mg/kg cardonilizumab, 14 days for 1 course. Group 2:1.8mg /mg LM-302 was treated for 1 course for 14 days. Group 3: 6 mg/kg cardonilizumab for 14 days was a course of treatment; RP2D LM-302 is 1 course of treatment for 14 days.

Candonilimab in Combination With LM-302 for Claudin 18.2 Positive-advanced Biliary Tract Cancer After Failure of Standard of Chemotherapy and PD1/PD-L1 Antibody

Two Stage, Multi-center Trial of Candonilimab in Combination With LM-302 for Treatment of Patients With Claudin 18.2 Positive-advanced Biliary Tract Cancer After Failure of Standard of Chemotherapy and PD1/PD-L1 Antibody

Objective response rate (ORR) in patients with Claudin18.2-positive treated with cardonillizumab combined with LM302 (RECIST 1.1)(Phase II)

Safety of cardonilizumab in combination with different doses of LM-302 in patients with advanced BTC

Shanghai Zhongshan Hospital

Carcinoma, Squamous Cell

Esophageal Neoplasms

Esophageal Squamous Cell Carcinoma

Head and Neck Neoplasms

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

Paclitaxel

Albumin-Bound Paclitaxel

Cisplatin

Immunomodulating Agents

In this group, the patients were given 2 cycles of inductive therapy of cardonilizumab combined with chemotherapy, followed by concurrent chemoradiotherapy with two cycles of nab-paclitaxel and cisplatin plus radiotherapy of 50-50.4 Gy. After clinical evaluation, surgery was feasible for a part of patients.

Two cycles of Inductive therapy： nab-paclitaxel 250mg/ m2+cisplatin 75mg/ m2+Cardonilizumab 10mg/kg，ivgtt，3 weeks per cycle for 2 cycles

Cardonilizumab

Chemoradiotherapy ± immunotherapy：

* PTV: 50-50.4Gy/1.8-2Gy/25-28fractions ②nab-paclitaxel 100mg+cisplatin 25mg/ m2, d1, every 7 days for 3-5 weeks ③Cardonilizumab 10mg/kg，ivgtt，3 weeks per cycle for 2 cycles

Chemoradiotherapy ±immunotherapy

Surgery was evaluated after concurrent chemoradiotherapy according to patients willing and the surgeons' assessment. If patients were accessed with unresectable disease after radiotherapy or refused to receive surgery, Cardonilizumab would be administered for 2 years or until disease progression.

Radical surgery

Xin Wang, M.D.

Xiaomin Wang, M.D.

Xiaomei Liu, M.D.

Xin Wang, MD

Xin Wang

Although unprecedented advances have been made in the field of esophageal cancer in recent decades, the prognosis for patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains extremely poor, accounting for 30-40% of overall survival at 5 year. In recent years, multimodal treatments have proven to be an appropriate therapeutic approach for locally advanced ESCC. Recently, immunotherapy developed rapidly. The purpose of this study was to observe the efficacy and safety of cardonilizumab combined with chemoradiotherapy in the treatment of locally advanced ESCC.

Induction Chemoimmunotherapy Combined With Chemoradiotherapy in Esophageal Cancer

Efficacy and Safety of Inductive Chemoimmunotherapy Followed by Chemoradiotherapy With or Without Surgery in Locally Advanced Esophageal Squamous Cell Cancer: a Single-arm, Prospective, Phase II Trial

Time from treatment initiation to locoregional or distant recurrence, or death from any cause.

The 1-year OS rate was defined as the proportion of patients who still alive within one year from treatment initiation.

In terms of adverse events of radiation, chemotherapy and immunotherapy

The 1-year rate was defined as the proportion of patients who did not have any locoregional recurrence from treatment initiation.

The 1-year rate was defined as the proportion of patients who did not have any distant metastasis from treatment initiation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Candonilimab in Combination With LM-302 for Claudin 18.2 Positive-advanced Biliary Tract Cancer After Failure of Standard of Chemotherapy and PD1/PD-L1 Antibody	NCT05994001	Biliary Tract C... Candonilimab Claudin 18.2	cardonilizumab LM-302	18 Years -	Shanghai Zhongshan Hospital
Candonilimab in Combination With LM-302 for Claudin 18.2 Positive-advanced Biliary Tract Cancer After Failure of Standard of Chemotherapy and PD1/PD-L1 Antibody	NCT05994001	Biliary Tract C... Candonilimab Claudin 18.2	cardonilizumab LM-302	18 Years -	Shanghai Zhongshan Hospital
Induction Chemoimmunotherapy Combined With Chemoradiotherapy in Esophageal Cancer	NCT06421376	Esophageal Canc... Immunotherapy Induction Thera... Chemoradiothera... Surgery	Cardonilizumab Chemoradiothera... Radical surgery	18 Years - 80 Years	Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Spots Global Cancer Trial Database for cardonilizumab