A Study of DS-8201a in Human Epidermal Growth Factor Receptor2 (HER2)-Expressing Colorectal Cancer

Overview

About this study

The purpose of this study is to test the safety and effectiveness of DS-8201a for participants with HER2-expressing advanced colorectal cancer.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Please contact the study team to discuss whether or not you are eligible to participate in a study.

Inclusion Criteria:

  • Age:  20 years old in Japan; ≥ 18 years old in other countries.
  • Pathologically documented unresectable, recurrent, or metastatic colorectal adenocarcinoma. Until sponsor’s notification to the study sites, subject must be a RAS/BRAF wild-type cancer.
  • Received at least 2 prior regimens of standard treatment.  The following therapies must be included in prior lines of therapy:
    • Fluoropyrimidine, irinotecan, and oxaliplatin;
    • In subjects with RAS wild-type, anti-EGFR antibody.
  • Is willing and able to provide an adequate archival tumor sample available for tissue screening to confirm HER2 status by Central Laboratory. If any anti-HER2 therapies (including pan-human epidermal growth factor receptor agents and study
  • drugs) were received, tumor samples used should come from post anti-HER2 therapy.
  • Appropriate HER2 expression assessed by Central Laboratory per Cohort setting:
    • Cohort A: HER2 IHC 3+ or IHC 2+/ISH +.
    • Cohort B: HER2 IHC 2+/ISH –.
    • Cohort C: HER2 IHC 1+.
  • Presence of at least 1 measurable lesion assessed by the investigator based on RECIST version 1.1.
  • Has ECOG PS of 0 to 1.
  • Has LVEF 50% within 28 days before enrollment (study drug treatment).
  • Has adequate organ function within 14 days before enrollment (study drug treatment), defined as:
  • Adequate bone marrow function
    • Platelet count ≥ 100,000/mm^3 (Platelet transfusion is not allowed within 1 week prior to screening assessment).
    • Hemoglobin ≥ 9.0 g/dL (Red blood cell transfusion is not allowed within 1 week prior to screening assessment).
    • Absolute neutrophil count ≥ 1500/mm3 (G-CSF administration is not allowed within 1 week prior to screening assessment).
  • Adequate renal function
    • Creatinine Creatinine clearance ≥ 30 mL/min as calculated using the Cockcroft-Gault equation.
  • Adequate hepatic function
    • Alanine aminotransferase (ALT);
    • Aspartate aminotransferase (AST) ≤ 5 × upper limit of normal (ULN);
    • Total bilirubin ≤ 1.5 × ULN if no liver metastases or < 3 x ULN in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.
  • Adequate blood clotting function
    • International normalized ratio/Prothrombin time and activated partial thromboplastin time ≤ 1.5 × ULN.
  • Has adequate treatment washout period before enrollment (study treatment), defined as:
    • Major surgery > 4 weeks;
    • Radiation therapy > 4 weeks (if palliative stereotactic radiation therapy without abdominal, >2 weeks);
    • Chemotherapy (including antibody drug therapy, retinoid therapy) > 3 weeks (> 2 weeks or 5 half-lives before study drug treatment, whichever is longer, for small-molecule targeted agents such as 5-fluorouracil-based agents, folinate agents, weekly paclitaxel; >4 weeks: Abs (eg, bevacizumab, cetuximab and panitumumab, ramucirumab); >6 weeks for nitrosureas or mitomycin C;
    • Immunotherapy > 4 weeks;
    • Cytochrome P450 (CYP) 3A4 strong inhibitor, OATP inhibitor > 3 elimination half-lives of the inhibitor.
  • Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 4.5 months after the last dose of study drug.
  • Methods considered as highly effective methods of contraception include:
    • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
      • Oral;
      • Intravaginal;
      • Transdermal.
    • Progestogen-only hormonal contraception associated with inhibition of ovulation:
      • Oral;
      • Injectable;
      • Implantable;
      • Intrauterine device;
      • Intrauterine hormone-releasing system;
      • Bilateral tubal occlusion;
      • Vasectomized partner;
      • Complete and true sexual abstinence defined as abstinence when it is in line with the preferred and usual lifestyle of the subject. Subjects in this study should refrain from heterosexual intercourse during and upon completion of  the study and for at least 4.5 months after the last dose of study drug. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to study drug, and withdrawal are not acceptable methods of contraception.
  • Non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone > 40 mIU/mL and estradiol < 40 pg/mL [<147 pmol/L] is confirmatory). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
  • Male subjects must not freeze or donate sperm starting at Screening and throughout the study period, and at least 4.5 months after the final study drug administration. Preservation of sperm should be considered prior to enrolment in this study.
  • Female subjects must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study treatment period, and for at least 4.5 months after the final study drug administration.
  • Must have provided informed consent for study participation before performance of any study-specific procedures or tests.
  • Subjects should be able and willing to comply with protocol visits and procedures.

Exclusion Criteria: 

  • Medical history of myocardial infarction within 6 months before enrollment (study treatment), symptomatic congestive heart failure (New York Heart Association Class II to IV), troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to enrollment (study treatment).
  • Has a corrected QT interval (QTcF) prolongation to >470 ms (females) or > 450 ms (males) based on average of the screening triplicate 12-lead ECG. The QT intervals will be corrected for heart rate by Fridericia’s formula (QTcF = QT/[RR]).
  • Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
  • Has clinically significant corneal disease in the opinion of the investigator.
  • Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.
  • Has multiple primary malignancies within 3 years, except adequately resected nonmelanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated.
  • Has history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
  • Has an uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals.
  • Has substance abuse or any other medical conditions that would increase the safety risk to the subject or interfere with participation of the subject or evaluation of the clinical study in the opinion of the Investigator.
  • Has known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. Subjects should be tested for HIV prior to enrollment (study treatment) if required by local regulations or institutional review board (IRB)/ethics committee (EC).
  • Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline. Subjects with chronic Grade 2 toxicities may be eligible per the discretion of the Investigator after consultation with the Sponsor Medical Monitor or designee (e.g., Grade 2 chemotherapy-induced neuropathy).
  • Is pregnant or breastfeeding, or planning to become pregnant.
  • Prior treatment with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor.
  • Social, familial, or geographical factors that would interfere with study participation or F/U.
  • Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the investigator.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Jason Starr, D.O.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Jason Starr, D.O.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Jason Starr, D.O.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions