JS212 Combination Therapies in Metastatic Colorectal Cancer

An Open-label, Multicenter Phase 2 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of JS212 Combination Therapies in Patients With Metastatic Colorectal Cancer

This is an open-label, multicenter Phase 2 clinical study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of JS212-based combination therapies in patients with metastatic colorectal cancer (mCRC).

JS212 is a bispecific antibody-drug conjugate (ADC) targeting epidermal growth factor receptor (EGFR) and HER3 with a topoisomerase I inhibitor payload. Preclinical and early clinical data suggest that dual targeting of EGFR and HER3 may enhance antitumor activity and overcome resistance mechanisms associated with EGFR- or HER2-directed therapies.

This study will investigate JS212 in combination with capecitabine, with or without Bevacizumab, and JS212 in combination with chemotherapy (XELOX: capecitabine and oxaliplatin), with or without the PD-1/VEGF bispecific antibody JS207, in patients with mCRC.

The study will assess safety, determine the recommended Phase 3 dose (RP3D), and evaluate preliminary antitumor activity of the combination regimens.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: JS212; Drug: Capecitabine; Drug: Bevacizumab; Drug: Oxaliplatin; Drug: JS207

Detailed Description

JS212 is a bispecific antibody-drug conjugate (ADC) targeting epidermal growth factor receptor (EGFR) and HER3, conjugated with a topoisomerase I inhibitor payload. Activation of EGFR and HER3 signaling pathways plays an important role in tumor development and resistance to anticancer therapies. Dual targeting of these pathways may enhance antitumor activity and broaden the population that may benefit from treatment. Early clinical data from study JS212-001-I/II have demonstrated promising safety and antitumor activity of JS212.

In addition, ADCs may induce immunogenic cell death and enhance antitumor immune responses. Combination therapy with immune checkpoint inhibitors may further enhance therapeutic efficacy. JS207 is a bispecific antibody targeting programmed death-1 (PD-1) and vascular endothelial growth factor (VEGF), which may provide synergistic antitumor effects by simultaneously modulating immune checkpoint signaling and tumor angiogenesis.

This study will evaluate JS212 in combination with capecitabine, with or without Bevacizumab, and JS212 in combination with chemotherapy (capecitabine and oxaliplatin, XELOX), with or without JS207, in patients with mCRC.

The study includes 4 cohorts:

Cohort 1: JS212 in combination with capecitabine. A dose-escalation phase using a Bayesian optimal interval (BOIN) design will be conducted to determine the maximum tolerated dose (MTD) and recommended Phase 3 dose (RP3D), followed by a dose-expansion phase to further evaluate safety and efficacy.

Cohort 2: JS212 in combination with capecitabine and Bevacizumab. A safety run-in phase will be conducted to evaluate tolerability of the triple combination, followed by a dose-expansion phase to further assess safety and preliminary antitumor activity.

Cohort 3: JS212 in combination with XELOX chemotherapy. safety run-in phase will be conducted to evaluate tolerability of the triple combination, followed by a dose-expansion phase to further assess safety and preliminary antitumor activity.

Cohort 4: JS212 in combination with XELOX chemotherapy and JS207. A safety run-in phase will be conducted to evaluate tolerability of the triple combination, followed by a dose-expansion phase to further assess safety and preliminary antitumor activity.

Eligible participants include adults with histologically confirmed metastatic colorectal adenocarcinoma that is microsatellite stable or mismatch repair proficient and who have not received prior systemic therapy for advanced disease.

The study will evaluate safety, pharmacokinetics, immunogenicity, and preliminary efficacy outcomes including objective response rate (ORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) based on RECIST version 1.1.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ying Zhang, Master; Phone Number: 86 18616904609; Email: ying_zhang2@junshipharma.com
• Study Contact Backup: Name: Huiyu Lan, Master; Phone Number: 86 15000239047; Email: huiyu_lan@junshipharma.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200123
      • Recruiting
      • Shanghai East Hospital
      • Contact: Yong Gao, Ph.D; Phone Number: 86 21-38804518; Email: drgaoyong@163.com
      • Principal Investigator: Yong Gao, Ph.D

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1Participants must meet the following key criteria
• Adults aged 18-75 years with histologically confirmed metastatic colorectal adenocarcinoma
• Microsatellite stable (MSS) or mismatch repair proficient (pMMR) disease
• No prior systemic therapy for advanced or metastatic disease
• At least one measurable lesion according to RECIST v1.1
• ECOG performance status 0-1
• Adequate hematologic, hepatic, renal, and coagulation function
• Life expectancy ≥12 weeks
• Willingness to provide tumor tissue samples for biomarker analyses
• Ability to provide written informed consent

Exclusion Criteria:

• Participants meeting any of the following criteria will be excluded
• Prior treatment with EGFR- or HER3-targeted antibody-drug conjugates or topoisomerase I inhibitor-based ADCs
• Recent major surgery, radiotherapy, or systemic anticancer therapy prior to study treatment
• Active or uncontrolled infections or significant cardiovascular disease
• Known active central nervous system metastases
• History of autoimmune disease requiring systemic therapy
• Significant bleeding disorders or high risk of hemorrhage
• Active viral infections such as uncontrolled hepatitis B, hepatitis C, or HIV
• Any other serious medical or psychiatric condition that may interfere with study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JS212 + Capecitabine; Participants receive JS212 in combination with Capecitabine.	Drug: JS212; Bispecific antibody-drug conjugate targeting EGFR and HER3; Drug: Capecitabine; Oral fluoropyrimidine chemotherapy
Experimental: JS212 +Capecitabine+ Bevacizumab; Participants receive JS212 in combination with Capecitabine and Bevacizumab	Drug: JS212; Bispecific antibody-drug conjugate targeting EGFR and HER3; Drug: Capecitabine; Oral fluoropyrimidine chemotherapy; Drug: Bevacizumab; Humanized anti-VEGF monoclonal antibody
Experimental: JS212 + XELOX; Participants receive JS212 in combination with XELOX chemotherapy (capecitabine plus oxaliplatin)	Drug: JS212; Bispecific antibody-drug conjugate targeting EGFR and HER3; Drug: Capecitabine; Oral fluoropyrimidine chemotherapy; Drug: Oxaliplatin; Platinum-based chemotherapy administered intravenously
Experimental: JS212 + XELOX + JS207; Participants receive JS212 in combination with XELOX chemotherapy and JS207	Drug: JS212; Bispecific antibody-drug conjugate targeting EGFR and HER3; Drug: Capecitabine; Oral fluoropyrimidine chemotherapy; Drug: Oxaliplatin; Platinum-based chemotherapy administered intravenously; Drug: JS207; Bispecific antibody targeting PD-1 and VEGF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed objective response rate (ORR)	Proportion of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1.	Up to approximately 12 months
Safety and Tolerability(AEs)	Incidence and severity of adverse events (AEs) assessed according to CTCAE.	From first dose up to approximately 90 days after last dose
Safety and Tolerability(SAEs)	Incidence and severity of serious adverse events (SAEs)assessed according to CTCAE.	From first dose up to approximately 90 days after last dose
Safety and Tolerability(DLTs)	Incidence and severity dose-limiting toxicities (DLTs) assessed according to CTCAE.	From first dose up to approximately 90 days after last dose
Maximum Tolerated Dose (MTD)	Determination of MTD for JS212 combination therapy.	Up to approximately 6 months
Recommended Phase 3 Dose (RP3D)	Determination of RP3D for JS212 combination therapy.	Up to approximately 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed objective response rate (DCR)	The DCR is defined as the proportion of subjects whose Best Overall Response (BOR) is Complete Response (CR), Partial Response (PR), or Stable Disease (SD).	Up to approximately 12 months
Investigator-assessed Duration of Response (DoR)	The DoR is defined as the time from the first occurrence of CR or PR to the first occurrence of Progressive Disease (PD) or death (whichever occurs first). The DoR is only applicable to subjects whose BOR is CR or PR.	Up to approximately 12 months
Investigator-assessed Progression-Free Survival (PFS)	The PFS is defined as the time from the first administration of the drug to the first documented disease progression (PD) according to the RECIST v1.1 criteria or death due to any disease (whichever occurs first).	Up to approximately 12 months
Investigator-assessed overall survival (OS)	The OS is defined as the time from the first administration of the drug to death due to any cause.	Up to approximately 20 months
PK of Cmax	Maximum Observed Plasma Concentration (Cmax) of JS212 and JS207	Up to approximately 12 months
PK of AUC	Area Under the Concentration-Time Curve of JS212 and JS207	Up to approximately 12 months
PK of half-time	Terminal Elimination Half-life of JS212 and JS207	Up to approximately 12 months
Immunogenicity	Incidence of anti-drug antibodies (ADA) and neutralizing antibodies.	Up to approximately 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The potential biomarker EGFR	To explore the correlation between screening baseline levels of potential biomarker EGFR and clinical efficacy of JS212 combination therapy. Biomarkers will be assessed only at screening. Screening	Up to approximately 1 months
The potential biomarker HER3	To explore the correlation between screening baseline levels of potential biomarker HER3 and clinical efficacy of JS212 combination therapy. Biomarkers will be assessed only at screening. Screening	Up to approximately 1 months

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.
• Investigators: Study Director: Zhenyu Xu, Doctor, Medical director

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): March 30, 2028

Study Registration Dates

• First Submitted: March 20, 2026
• First Submitted That Met QC Criteria: March 26, 2026
• First Posted (Actual): March 31, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; Bevacizumab
• Other Study ID Numbers: JS212-005-II-CRC

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