Advanced Colorectal Cancer Expressing HER2Phase 2HORIZON-CRC221NCT07796763
A Global Trial of Trastuzumab Rezetecan (SHR-A1811) in Combination With Chemotherapy and Bevacizumab as First-Line Treatment in Patients With Advanced Colorectal Cancer Expressing HER2
A Phase 2 study testing Trastuzumab Rezetecan (SHR-A1811) injection; high dose and Trastuzumab Rezetecan (SHR-A1811) injection; low dose in people with Advanced Colorectal Cancer Expressing HER2, run by Jiangsu HengRui Medicine Co., Ltd. at 1 site in United States.
Trial summary
This global study is being conducted to evaluate the safety and determine the recommended phase 3 dose of trastuzumab rezetecan in combination with mFOLFOX6 chemotherapy (dose level -1) and bevacizumab as first-line treatment in participants with advanced colorectal cancer that expresses HER2, including but not… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Colorectal Cancer Expressing HER2
- What is being tested?
- Trastuzumab Rezetecan (SHR-A1811) injection; high dose and Trastuzumab Rezetecan (SHR-A1811) injection; low dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2026to 1 Nov 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ECOG performance status score of 0 or 1.
- Histologically or cytologically confirmed unresectable, recurrent, or metastatic colorectal adenocarcinoma that is HER2-positive. "HER2-positive" indicates IHC 2+ or 3+, or HER2 (ERBB2) amplification by NGS at a CLIA-certified or ISO-accredited laboratory. HER2 IHC 2+/3+ should be based on gastric cancer criteria.
- Either have not received any prior systemic anti-tumor therapy (including, but not limited to, systemic chemotherapy, molecular targeted drug therapy, immunotherapy, biotherapy, or other investigational agents), or, if previously treated with neoadjuvant or adjuvant therapy, have first documented recurrence or metastasis >6 months after the last dose of neoadjuvant or adjuvant therapy. Participants known to have dMMR or high-level MSI-H are excluded unless the investigator determines they are unsuitable for anti-PD-1/PD-L1 therapy. Participants known to have BRAF V600 mutation are excluded unless the investigator determines they are unsuitable for BRAF-targeting therapy. Note that participants may have received a maximum of 2 doses of mFOLFOX6 with or without bevacizumab in the locally advanced/unresectable or metastatic setting prior to randomization.
- Have at least one measurable lesion according to the RECIST version 1.1. Measurable lesions should not have received prior local therapy such as radiotherapy (lesions located within a previous radiotherapy field can be considered as target lesions if progression is confirmed).
Who cannot join
- Prior Treatments:
- Prior treatment with anti-HER2 ADCs featuring exatecan or its derivatives as the payload (a topoisomerase I inhibitor), such as trastuzumab deruxtecan (Enhertu®, DS-8201a).
- Treatment with any investigational drug or therapy not yet approved for marketing within 4 weeks prior to the first dose of the IMP.
- Systemic anti-tumor therapy within 4 weeks prior to the first dose of the IMP, including chemotherapy, biotherapy, targeted therapy, or immunotherapy. For small molecule targeted therapies, a washout period of at least 5 half-lives or 7 days (whichever is longer) from the last dose is required before the first dose of the IMP. Note that participants may have received a maximum of 2 doses of mFOLFOX6 with or without bevacizumab in the locally advanced/unresectable or metastatic setting prior to randomization.
- Palliative radiotherapy completed within 2 weeks prior to the first dose of the IMP.
- Major surgery within 4 weeks prior to the first dose of the IMP or planned elective surgery during the trial period. Minor traumatic procedures (e.g., needle biopsy, endoscopy, drainage) within 7 days prior. Presence of non-healed wounds (severe, non-healing, or dehisced) or untreated fractures.
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- Use of aspirin (>325 mg/day), dipyridamole, ticlopidine, clopidogrel, cilostazol, or other drugs known to inhibit platelet function within 1 week prior to the first dose of the IMP.
- Administration of live attenuated vaccines within 4 weeks prior to the first dose of the IMP, or anticipated requirement for such vaccines during the study treatment period.
- History of hypersensitivity to monoclonal antibodies, any component of the trastuzumab rezetecan formulation, fluorouracil, levo-leucovorin (or leucovorin), oxaliplatin, bevacizumab, or related drugs.
- Presence of Grade >1 peripheral sensory neuropathy.
- History of hemoptysis (approximately ≥2.5 mL of fresh blood in one episode) within 3 months prior to the first dose of the IMP.
- Tumor encasement or invasion of major blood vessels (e.g., pulmonary artery, superior vena cava) as indicated by CT or MRI.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
MD Anderson Cancer Center
Houston, Texas, 77030
Kanwal Raghav, MD
About this study
Official title: A Global, Multicenter, Randomized, Dose-Optimization Phase II Study of Trastuzumab Rezetecan (SHR-A1811) in Combination With mFOLFOX6 (-1) and Bevacizumab as First-Line Treatment in Patients With HER2-Positive Advanced Colorectal Cancer (HORIZON-CRC221)
This global study is being conducted to evaluate the safety and determine the recommended phase 3 dose of trastuzumab rezetecan in combination with mFOLFOX6 chemotherapy (dose level -1) and bevacizumab as first-line treatment in participants with advanced colorectal cancer that expresses HER2, including but not limited to HER2 immunohistochemistry (IHC) 2+ "equivocal" or 3+ "positive" based on gastric cancer criteria, focused on the Western population. Encouraging data in efficacy and safety with trastuzumab rezetecan in a similar setting in China (NCT06015048) were presented at 2026 American Society of Clinical Oncology annual meeting.
- Being tested
- Trastuzumab Rezetecan (SHR-A1811) injection; high dose, Trastuzumab Rezetecan (SHR-A1811) injection; low dose
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab Rezetecan (SHR-A1811) injection; high doseDrug
Trastuzumab Rezetecan (SHR-A1811) injection; high dose
Trastuzumab Rezetecan (SHR-A1811) injection; low doseDrug
Trastuzumab Rezetecan (SHR-A1811) injection; low dose
| Study group | Role | What they receive |
|---|---|---|
| Treatment group A | Experimental | Trastuzumab Rezetecan (SHR-A1811; high dose) in Combination with mFOLFOX6 (-1) and Bevacizumab injection Receives: Drug: Trastuzumab Rezetecan (SHR-A1811) injection; high dose |
| Treatment group B | Experimental | Trastuzumab Rezetecan (SHR-A1811; low dose) in Combination with mFOLFOX6 (-1) and Bevacizumab injection. Receives: Drug: Trastuzumab Rezetecan (SHR-A1811) injection; low dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events
Measured: about two years
Determination of the recommended phase 3 dose
Measured: about two years
Secondary outcomes (5)
Objective response rate, as assessed by the investigator
Measured: about two years
Disease control rate, as assessed by the investigator
Measured: about two years
Duration of response, as assessed by the investigator
Measured: about two years
Progression free survival, as assessed by the investigator
Measured: about two years
Overall survival
Measured: about two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2026
- Study start1 Nov 2026 (estimated)
- Primary completion1 May 2028 (estimated)
- Study completion1 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Colorectal Cancer Expressing HER2Studies of the same condition, open and under way.
- More trials run by Jiangsu HengRui Medicine Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Trastuzumab Rezetecan (SHR-A1811), mFOLFOX6 (dose level -1) and Bevacizumab intravenous injection
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07796763
- Sponsor's protocol ID
- SHR-A1811-221
- Acronym
- HORIZON-CRC221
- Status last verified
- Aug 2026
- First submitted
- 28 Aug 2026
- Last updated
- 1 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided