JS212 Combination Therapies in Metastatic Colorectal Cancer

NCT07503756 | Recruiting Phase 2

• 1 other identifier: JS212-005-II-CRC
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (8)

• Investigator-assessed objective response rate (DCR)

  Up to approximately 12 months

• Investigator-assessed Duration of Response (DoR)

  Up to approximately 12 months

• Investigator-assessed Progression-Free Survival (PFS)

  Up to approximately 12 months

• Investigator-assessed overall survival (OS)

  Up to approximately 20 months

• PK of Cmax

  Up to approximately 12 months

Other Outcomes (2)

• The potential biomarker EGFR

  Up to approximately 1 months

• The potential biomarker HER3

  Up to approximately 1 months

Study Arms (4)

JS212 + Capecitabine

EXPERIMENTAL

Participants receive JS212 in combination with Capecitabine.

Drug: JS212; Drug: Capecitabine

JS212 +Capecitabine+ Bevacizumab

EXPERIMENTAL

Participants receive JS212 in combination with Capecitabine and Bevacizumab

Drug: JS212; Drug: Capecitabine; Drug: Bevacizumab

JS212 + XELOX

EXPERIMENTAL

Participants receive JS212 in combination with XELOX chemotherapy (capecitabine plus oxaliplatin)

Drug: JS212; Drug: Capecitabine; Drug: Oxaliplatin

JS212 + XELOX + JS207

EXPERIMENTAL

Participants receive JS212 in combination with XELOX chemotherapy and JS207

Drug: JS212; Drug: Capecitabine; Drug: Oxaliplatin; Drug: JS207

Interventions

JS212 DRUG

Bispecific antibody-drug conjugate targeting EGFR and HER3

JS212 + Capecitabine; JS212 + XELOX; JS212 + XELOX + JS207; JS212 +Capecitabine+ Bevacizumab

Capecitabine DRUG

Oral fluoropyrimidine chemotherapy

JS212 + Capecitabine; JS212 + XELOX; JS212 + XELOX + JS207; JS212 +Capecitabine+ Bevacizumab

Bevacizumab DRUG

Humanized anti-VEGF monoclonal antibody

JS212 +Capecitabine+ Bevacizumab

Oxaliplatin DRUG

Platinum-based chemotherapy administered intravenously

JS212 + XELOX; JS212 + XELOX + JS207

JS207 DRUG

Bispecific antibody targeting PD-1 and VEGF

JS212 + XELOX + JS207

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shanghai Junshi Bioscience Co., Ltd.: lead

Study Sites (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200123, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Capecitabine; Bevacizumab; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals

Study Officials

• Zhenyu Xu, Doctor

  Medical Director

  STUDY DIRECTOR

Central Study Contacts

Ying Zhang, Master

CONTACT

86 18616904609; ying_zhang2@junshipharma.com

Huiyu Lan, Master

CONTACT

86 15000239047; huiyu_lan@junshipharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phaseII, open-label, multicenter study in previously untreated MSS/pMMR advanced colorectal cancer, evaluating JS212+Capecitabine (Cohort 1), JS212+Capecitabine+Bevacizumab (Cohort 2), JS212 + XELOX (Cohort 3) and JS212 + XELOX + JS207 (Cohort 4). Cohort 1: A dose-escalation phase (JS212 Q3W +Capecitabine) will select 1-2 RP2Ds, followed by a dose-expansion phase to assess safety, efficacy. Cohort 2: After confirming Cohort 1's RP2D, a safety lead-in phase will evaluate JS212 (RP2D) + Capecitabine + Bevacizumab Q3W. A dose-expansion phase will further assess safety, efficacy. Cohort 3: After confirming Cohort 1's RP2D, a safety lead-in phase will evaluate JS212 (RP2D) + XELOX Q3W. A dose-expansion phase will further assess safety, efficacy. Cohort 4: After confirming Cohort 1's RP2D, a safety lead-in phase will evaluate JS212 (RP2D) + XELOX + JS207 Q3W. A dose-expansion phase will further assess safety, efficacy.

Study Record Dates

• First Submitted: March 20, 2026
• First Posted: March 31, 2026
• Study Start: April 25, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): March 30, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)