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Colorectal NeoplasmsPhase 2NCT05493683

Disitamab Vedotin Combined With Tislelizumab in Advanced HER2 Positive Colorectal Cancer

A Phase 2 study testing Disitamab vedotin and Tislelizumab in people with Colorectal Neoplasms, run by The First Affiliated Hospital with Nanjing Medical University at 6 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Among patients with colonrectal cancer, 5% were HER-2 positive, but the immunohistochemical results were mostly HER-2 2 +, which did not meet the indications of HER-2 targeting drugs. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Neoplasms
What is being tested?
Disitamab vedotin and Tislelizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
6 sitesChina
Study dates
1 Aug 2022to Jul 2025
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Signed the consents voluntarily;
  • All genders, age 18 or above;
  • Histological or cytological documentation of local advanced or metastatic unresectable colorectal carcinoma;
  • Patients with HER-2 overexpression (HER-2 IHC 2+ or IHC 3+) detected by immunohistochemistry; Resampling is recommended for samples over 3 years.
  • Subjects must have failed at treatments including fluoropyrimidine, oxaliplatin and irinotecan; For adjuvant or neoadjuvant chemotherapy, if disease progression occurs during treatment or within 6 months after treatment, it will be recorded as a first-line treatment;
  • Patients who have used anti-PD-1 or anti-PD-L1 inhibitors can be selected after stopping the treatment for more than 6 months; Patients who have used other anti HER-2 drugs with different mechanisms can be selected.
Show all 16Show fewer
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.is necessary
  • Life expectancy of at least 3 months.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  • Have sufficient heart, lung, liver and kidney functions, and the laboratory examination within 14 days before screening meets the following indicators:
  • Hemoglobin Hb ≥ 90 g/L ii. Neutrophil count ANC ≥ 1.5*10^9 /L iii. Platelet count PLT ≥ 80*10^9 /L iv. Albumin ALB ≥ 35 g/L v. Alanine aminotransferase ALT and aspartate aminotransferase AST ≤ 2.5 times the upper limit of the normal range, and liver metastasis patients ≤ 5 times the upper limit of the normal range.
  • Total bilirubin ≤ 1.5 times, or 2 times the upper limit of normal. vii. Creatinine Scr ≤ upper limit of normal range. viii. Prothrombin: PT-INR ≤ 2.3 or PT < 6 seconds compared with normal control
  • Subjects must complete the treatment and follow-up on schedule. according to the research plan.
  • No brain metastasis, no spinal cord compression.
  • Subjects agree to use blood samples for study analysis.
  • Women of childbearing age must be negative in pregnancy test and willing to take effective contraceptive measures during the study period.

Who cannot join

  • Subjects are severe malnutrition or need tube feeding.
  • Major surgery has been performed within 30 days before treatment.
  • Previous treatment with anti-PD-1 / PD-L1 inhibitor, anti-CTLA-4 inhibitor, ADC drugs targeting HER-2 such as RC48 and T-DM1 within 6 months.
  • Other malignant tumors within 2 years and without cure (Except for patients with other early-stage tumors, after radical treatment, whom the researchers assess the recurrence risk of in the short term is small);
  • Subjects have active autoimmune system diseases that need systemic hormone therapy or anti autoimmune drug therapy.
  • Subjects with immunodeficiency or receiving systemic steroid therapy (prednisone > 10 mg / day or other equivalent drugs) or other forms of immunosuppressive therapy 7 days before the first dose of combination therapy in this study;
Show all 16Show fewer
  • Subjects with active infection and still need systemic treatment 7 days before the first dose of therapy in this study.
  • Subjects with uncontrollable systemic diabetes.
  • Subjects with interstitial lung disease, non infectious pneumonia or pulmonary fibrosis;
  • Subjects who have received allogeneic organ or stem cell transplantation in the past.
  • Subjects allergic to the drugs or related components involved in this study.
  • Participating in other interventional clinical studies.
  • The previous anti-tumor related adverses do not return to grade 1 in CTCAE before the first combination therapy.
  • Subjects who have uncontrolled hypertension by drugs, that is, systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg.
  • Thrombotic or hemorrhagic tendency or history within 60 days before the first medication, regardless of the severity.
  • Any serious or unstable medical condition#mental illness or known active alcohol or drug abuse or dependence.

Trial locations and contacts

6 sites in 1 country.

Yanhong Gu, Dr contact

00862568306714

guluer@163.com

Shiyun Cui, Dr contact

6 sites in 1 country

China6 sites, 6 recruiting

  • Changzhou NO.2 People's Hospital

    Changzhou, Jiangsu, 150000

    Hua Jiang

    Recruiting

  • The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University

    Huai'an, Jiangsu, 150000

    Xiaomin Zhong

    Recruiting

  • The First Affiliated Hospital with Nanjing Medical University

    Nanjing, Jiangsu, 210029

    Yanhong Gu, Ph.D, 13813908678, guluer@163.com

    Yanhong Gu, Ph.D

    Recruiting

  • Fudan University Shanghai Cancer Center

    Shanghai, Shanghai Municipality

    Zhiyu Chen

    Recruiting

  • the Third Affiliated Hospital of Soochow University

    Suzhou, Jiangsu, 150000

    Wenwei Hu

    Recruiting

  • Xuzhou Central Hospital

    Xuzhou, Jiangsu, 150000

    Yuan Yuan

    Recruiting

Other trials in China

About this study

Official title: A Single Arm, Open Label, Multiple Center, Prospective Study of Disitamab Vedotin Combined With Tislelizumab in HER2 Positive Advanced Colorectal Cancer Failed at Least Two Lines of Systemic Treatment.

Among patients with colonrectal cancer, 5% were HER-2 positive, but the immunohistochemical results were mostly HER-2 2 +, which did not meet the indications of HER-2 targeting drugs. Disitamab Vedotin , which was listed in China last year, achieved similar results in HER-2 2+ and 3+, according to a clinical trial for breast cancer, suggesting that patients with colonrectal cancer may benefit from it. Tislelizumab is a PD-1 monoclonal antibody, which has been approved for a variety of tumors. It was reported that anti-HER-2 treatment can improve the tumor immune microenvironment and improve the efficacy of immunotherapy. At the same time, our previous studies showed that anti-PD-1 combined with Disitamab Vedotin can significantly inhibit the growth of colon tumor in mice. Therefore, Disitamab Vedotin and Tislelizumab were used in this study. This prospective clinical trial may bring new hope for the treatment of HER-2 positive CRC patients.

Being tested
Disitamab vedotin, Tislelizumab
Keywords
Colorectal Cancer, Antibody Drug Conjugate, Disitamab Vedotin, Tislelizumab
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Disitamab vedotinDrug

    Also called RC48

    2.0mg/kg，q2w

  • TislelizumabDrug

    400mg，q6w

Study groups in NCT05493683
Study groupRoleWhat they receive
Combination of Disitamab Vedotin and TislelizumabExperimentalDisitamab Vedotin 2.0mg/kg q2w+Tislelizumab 400mg q6w. The treatment of Disitamab Vedotin + Tislelizumab will continue until the tumor progression confirmed by imaging, or up to 2 years, or intolerable toxic reactions, or other conditions determined by the researchers.
Receives: Drug: Disitamab vedotin; Drug: Tislelizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate(ORR)

    The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR)

    Measured: up to 2 years

Secondary outcomes (5)

  1. Progression-free Survival(PFS)

    PFS was defined as the time from assignment to disease progression radiological/clinical or death due to any cause, whichever occurs first. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation.

    Measured: From date of subjects until the date of first documented progression or death from any cause, whichever came first, assessed up to 24 months

  2. Overall Survival (OS)

    OS is defined as the time from date of assignment to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.

    Measured: From assignment of the first subject until 32 death events observed, up to 2 years.

  3. Disease control rate (DCR)

    DCR is defined as the percentage of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD).

    Measured: up to 2 years

  4. Safety and Feasibility

    Safety is defined as the incidence of Grade 3-4 Treatment-Related Adverse Events (TRAEs) from the day of neoadjuvant therapy to 30 days after surgery or within 90 days after last neoadjuvant treatment. Feasibility of surgery is defined as the incidence of TRAEs causing surgery delay of ≥30 days and/or inoperable patients.Feasibility of surgery is defined as the incidence of TRAEs causing surgery delay of ≥30 days and/or inoperable patients.

    Measured: up to 2 years

  5. Duration of Response (DOR)

    DOR is defined as the time from randomization to disease progression or death in patients who achieve complete or partial response.

    Measured: up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2022
  2. Study start1 Aug 2022
  3. Primary completionJul 2025 (estimated)
  4. Study completionJul 2025 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05493683
Sponsor's protocol ID
KEEP-G 07
Status last verified
Oct 2022
First submitted
7 Aug 2022
Last updated
21 Oct 2022
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

    PubMed 30207593

  • Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25.

    PubMed 26808342

  • Diagnosis And Treatment Guidelines For Colorectal Cancer Working Group CSOCOC. Chinese Society of Clinical Oncology (CSCO) diagnosis and treatment guidelines for colorectal cancer 2018 (English version). Chin J Cancer Res. 2019 Feb;31(1):117-134. doi: 10.21147/j.issn.1000-9604.2019.01.07. No abstract available.

    PubMed 30996570

  • Messersmith WA. NCCN Guidelines Updates: Management of Metastatic Colorectal Cancer. J Natl Compr Canc Netw. 2019 May 1;17(5.5):599-601. doi: 10.6004/jnccn.2019.5014.

    PubMed 31117039

  • Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D'Hoore A, Diaz-Rubio E, Douillard JY, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Kohne CH, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Osterlund P, Oyen WJ, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taieb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016 Aug;27(8):1386-422. doi: 10.1093/annonc/mdw235. Epub 2016 Jul 5.

    PubMed 27380959

  • Piawah S, Venook AP. Targeted therapy for colorectal cancer metastases: A review of current methods of molecularly targeted therapy and the use of tumor biomarkers in the treatment of metastatic colorectal cancer. Cancer. 2019 Dec 1;125(23):4139-4147. doi: 10.1002/cncr.32163. Epub 2019 Aug 21.

    PubMed 31433498

  • Shirley M. Fruquintinib: First Global Approval. Drugs. 2018 Nov;78(16):1757-1761. doi: 10.1007/s40265-018-0998-z.

    PubMed 30357594

  • Oh DY, Bang YJ. HER2-targeted therapies - a role beyond breast cancer. Nat Rev Clin Oncol. 2020 Jan;17(1):33-48. doi: 10.1038/s41571-019-0268-3. Epub 2019 Sep 23.

    PubMed 31548601

  • Rakha EA, Pinder SE, Bartlett JM, Ibrahim M, Starczynski J, Carder PJ, Provenzano E, Hanby A, Hales S, Lee AH, Ellis IO; National Coordinating Committee for Breast Pathology. Updated UK Recommendations for HER2 assessment in breast cancer. J Clin Pathol. 2015 Feb;68(2):93-9. doi: 10.1136/jclinpath-2014-202571. Epub 2014 Dec 8.

    PubMed 25488926

  • Ruschoff J, Hanna W, Bilous M, Hofmann M, Osamura RY, Penault-Llorca F, van de Vijver M, Viale G. HER2 testing in gastric cancer: a practical approach. Mod Pathol. 2012 May;25(5):637-50. doi: 10.1038/modpathol.2011.198. Epub 2012 Jan 6.

    PubMed 22222640

  • Mar N, Vredenburgh JJ, Wasser JS. Targeting HER2 in the treatment of non-small cell lung cancer. Lung Cancer. 2015 Mar;87(3):220-5. doi: 10.1016/j.lungcan.2014.12.018. Epub 2015 Jan 8.

    PubMed 25601485

  • Siena S, Sartore-Bianchi A, Marsoni S, Hurwitz HI, McCall SJ, Penault-Llorca F, Srock S, Bardelli A, Trusolino L. Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer. Ann Oncol. 2018 May 1;29(5):1108-1119. doi: 10.1093/annonc/mdy100.

    PubMed 29659677

  • Valtorta E, Martino C, Sartore-Bianchi A, Penaullt-Llorca F, Viale G, Risio M, Rugge M, Grigioni W, Bencardino K, Lonardi S, Zagonel V, Leone F, Noe J, Ciardiello F, Pinto C, Labianca R, Mosconi S, Graiff C, Aprile G, Frau B, Garufi C, Loupakis F, Racca P, Tonini G, Lauricella C, Veronese S, Truini M, Siena S, Marsoni S, Gambacorta M. Assessment of a HER2 scoring system for colorectal cancer: results from a validation study. Mod Pathol. 2015 Nov;28(11):1481-91. doi: 10.1038/modpathol.2015.98. Epub 2015 Oct 9.

    PubMed 26449765

  • Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, Zagonel V, Leone F, Depetris I, Martinelli E, Troiani T, Ciardiello F, Racca P, Bertotti A, Siravegna G, Torri V, Amatu A, Ghezzi S, Marrapese G, Palmeri L, Valtorta E, Cassingena A, Lauricella C, Vanzulli A, Regge D, Veronese S, Comoglio PM, Bardelli A, Marsoni S, Siena S. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 Jun;17(6):738-746. doi: 10.1016/S1470-2045(16)00150-9. Epub 2016 Apr 20.

    PubMed 27108243

  • Meric-Bernstam F, Hurwitz H, Raghav KPS, McWilliams RR, Fakih M, VanderWalde A, Swanton C, Kurzrock R, Burris H, Sweeney C, Bose R, Spigel DR, Beattie MS, Blotner S, Stone A, Schulze K, Cuchelkar V, Hainsworth J. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2019 Apr;20(4):518-530. doi: 10.1016/S1470-2045(18)30904-5. Epub 2019 Mar 8.

    PubMed 30857956

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Disitamab vedotin and Tislelizumab in people with Colorectal Neoplasms, run by The First Affiliated Hospital with Nanjing Medical University at 6 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 21 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Yanhong Gu, Dr (00862568306714, guluer@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate(ORR) (time frame: up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05493683, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2022.

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