Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion

Description

Summary

This study is one single group of participants with non-small cell lung cancer (NSCLC) who have not been cured by other treatments. It is the first time the drug has been used in humans, and will be in two parts. The primary purpose of the parts are: - Dose Escalation: To investigate the safety and tolerability and to determine the maximum tolerated dose (MTD) and the recommended dose for expansion (RDE) of DS-1062a - Dose Expansion: To investigate the safety and tolerability of DS-1062a in additional solid tumors This study is expected to last approximately 6 years from the time the first participant is enrolled to the time the last subject is off the study. Study sites are located in both the United States and Japan. The number of treatment cycles is not fixed in this study. Participants who continue to benefit from the study treatment may continue, unless: - they withdraw - their disease gets worse - they experience unacceptable side effects.

Official Title

Phase 1, Two-part, Multicenter, Open-label, Multiple Dose, First-in-human Study of DS-1062a in Subjects With Advanced Solid Tumors (TROPION-PanTumor01)

Details

The dosage strength will change during the study but all participants will receive the same study drug. So the study is not a true 2-arm study, it is a 2-part study. In both parts, participants with pathologically documented unresectable advanced NSCLC and triple negative breast cancer (TNBC) who have been refractory to or relapsed from standard treatment or for which no standard treatment is available, will be enrolled. In Dose Expansion, additional indications (hormone receptor [HR]-positive human epidermal growth factor receptor 2 [HER2]-negative breast cancer, small cell lung cancer [SCLC], endometrial cancer, pancreatic adenocarcinoma, HER2-negative gastric/gastroesophageal junction [GEJ] cancer, esophageal cancer, head and neck squamous cell carcinoma [HNSCC], transitional cell carcinoma of the urothelium, colorectal cancer [CRC], platinum-resistant ovarian cancer, platinum-sensitive ovarian cancer, cervical cancer, and castration-resistant prostate cancer [CRPC]) may be evaluated, if the study treatment demonstrates acceptable safety, tolerability and efficacy in NSCLC participants. After the primary analysis, the main (registered) study will be considered complete, but data will be collected from participants who continue receiving study drug.

Keywords

Hormone Receptor Positive Breast Cancer Triple Negative Breast Cancer Non-small Cell Lung Cancer Other solid tumors Breast Neoplasms Carcinoma, Non-Small-Cell Lung Triple Negative Breast Neoplasms

Eligibility

You can join if…

Open to people ages 18 years and up

All Participants:

  • Has relapsed or progressed following local standard treatments or for which no standard treatment is available.
  • Consents to provide mandatory pre-treatment tumor tissue samples for the measurement of TROP2 and other biomarkers. There is no minimum TROP2 expression level required for inclusion.
  • Consents to undergo mandatory on-treatment biopsy if clinically feasible and not contraindicated at the time of on-treatment biopsy, and consents to provide the tumor tissue samples from on-treatment biopsy for the measurement of TROP2 level and other biomarkers.
  • Is aged ≥20 years old in Japan or ≥18 years old in other countries.
  • Has an Eastern Cooperative Oncology Group performance status 0-1.
  • Has a left ventricular ejection fraction (LVEF) ≥50% by either an ECHO or MUGA within 28 days before enrollment.
  • Has measurable disease based on RECIST version1.1.
  • Has adequate bone marrow reserve and organ function within 7 days before Cycle 1, Day
  • Has an adequate treatment washout period prior to Cycle 1, Day 1.
  • If of reproductive/childbearing potential, agrees to use a highly effective from of contraception or avoid intercourse during and upon completion of the study and for at least 7 months for females and 4 months for males after the last dose of study drug, and agrees not to retrieve, freeze or donate sperm or ova starting at Screening and throughout the study period, and at least 7 months for males and 4 months for males after the final study drug administration.
  • After being fully informed about their illness and the investigative nature of the protocol (including foreseeable risks and possible toxicities), is willing and able comply with the protocol and to provide written, ethics committee-approved informed consent form before performance of any study-specific procedures or examinations.
  • Has a life expectancy of ≥3 months.
  • Has no prior treatment with antibody drug conjugate with deruxtecan (including trastuzumab deruxtecan [T-DXd; DS-8201a] and patritumab deruxtecan [HER3-DXd; U31402])
  • Has no prior treatment with trophoblast cell surface antigen 2 (TROP2)-targeted therapy

NSCLC participants only:

  • Has a pathologically documented unresectable advanced NSCLC disease not amenable to curative therapy

TNBC participants only:

  • Has a pathologically documented advanced/unresectable or metastatic breast cancer with HR- (estrogen and progesterone receptor) negative disease and HER2 negative expression according to the American Society of Clinical Oncology - College of American Pathologists guidelines (ASCO-CAP)

HR positive, HER2-negative participants only:

  • Pathologically documented unresectable or metastatic breast cancer that is:
  • HER2-negative
  • Positive for estrogen receptor and/or progesterone receptor
  • Is documented refractory or resistant to endocrine therapy
  • Was previously treated with a minimum of 1 and a maximum of 3 prior lines of chemotherapy in the advanced/metastatic setting

Small-cell lung cancer (SCLC) participants only:

  • Pathologically documented unresectable or metastatic, and/or extensive-stage SCLC that was previously treated with 1 to 2 prior lines of therapy including platinum-based chemotherapy and immune checkpoint inhibitor
  • No prior exposure to topotecan

Endometrial cancer participants only:

  • Pathologically documented recurrent or persistent endometrial cancer that relapsed or progressed after any established and/or curative therapies, including at least 1 systemic therapy

Pancreatic adenocarcinoma participants only:

  • Pathologically documented unresectable or metastatic pancreatic cancer that was previously treated with at least 1 prior line of systemic therapy in neoadjuvant, adjuvant, locally advanced or metastatic setting

HER2-negative gastric/GEJ cancer participants only:

  • Pathologically documented unresectable or metastatic gastric/GEJ adenocarcinoma that was previously treated with at least 1 prior line of systemic therapy
  • No known history of HER2-overexpression (Immunohistochemistry [IHC] 0, IHC 1 or IHC 2+/ in situ hybridization [ISH]-negative) as classified by ASCO-CAP at any time

Esophageal cancer participants only:

  • Pathologically documented unresectable or metastatic esophageal cancer that:
  • Is squamous or adenocarcinoma
  • Was previously treated with at least 1 prior line of therapy including platinum-based chemotherapy

Head and neck squamous cell carcinoma (HNSCC) participants only:

  • Pathologically documented unresectable or metastatic HNSCC that was previously treated with 1-3 prior lines of therapy including platinum and ICI (in combination or sequential), in the advanced or metastatic setting

Transitional cell carcinoma of the urothelium participants only:

  • Pathologically documented unresectable, locally advanced or metastatic, transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra) that was previously treated with at least 1 prior line of therapy including platinum-based chemotherapy and ICI (in combination or sequential).
  • Was previously treated with enfortumab vedotin where available

Colorectal cancer (CRC) participants only:

  • Pathologically documented unresectable or metastatic CRC that was previously treated with, or were not considered candidates for, available therapies including fluoropyrimidine-based chemotherapy, an anti-vascular endothelial growth factor therapy, and an anti-epidermal growth factor (EGFR) therapy
  • Has not progressed or relapsed within 6 months of therapy with irinotecan

Platinum-resistant ovarian cancer participants only:

  • Pathologically documented unresectable or metastatic ovarian cancer that:
  • Is epithelial ovarian (including less-common histologies per National Comprehensive Cancer Network (NCCN)
  • Has relapsed or progressed within 6 months of platinum-based chemotherapy

Platinum-sensitive ovarian cancer participants only:

  • Pathologically documented unresectable or metastatic ovarian cancer that:
  • Is epithelial ovarian (including less-common histologies per NCCN guidelines), fallopian tube, or primary peritoneal presentation
  • Has relapsed or progressed at least 6 months after the most recent platinum-based chemotherapy

Cervical cancer participants only:

  • Pathologically documented unresectable or metastatic cervical cancer that relapsed or progressed after at least 1 prior line of systemic therapy

Castration-resistant prostate cancer participants only:

  • Pathologically documented unresectable or metastatic CRPC that:
  • Is adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology
  • Is surgically or medically castrated, with testosterone levels of less than 50 nanograms per deciliter
  • Objective progression by RECIST version 1.1 criteria for participants with measurable disease after androgen deprivation
  • Has relapsed or progressed after at least 1 of the following: abiraterone or enzalutamide
  • Has relapsed or progressed after at least 1, but not more than 2, cytotoxic chemotherapy regimens for metastatic castration resistant prostate cancer (mCRPC). At least 1 regimen must have contained a taxane. If a specific taxane was used more than once, the regimens containing the same taxane would be considered as 1 regimen in total.

You CAN'T join if...

  • Has a history of malignancy, other than a tumor type specified in the Inclusion Criteria, except (a) adequately resected non-melanoma skin cancer, (b) curatively treated in situ disease, or (c) other solid tumors curatively treated, with no evidence of disease for ≥3 years.
  • Has a history of myocardial infarction or unstable angina within 6 months before enrollment.
  • Has a medical history of congestive heart failure (New York Heart Association classes II-IV) or a serious cardiac arrhythmia requiring treatment.
  • Has a mean corrected QT interval (QTcF) prolongation to >470 ms based on average of the screening triplicate 12-lead ECGs.
  • 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.
  • Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
  • Has active human immunodeficiency virus infection that is uncontrolled (increasing plasma HIV RNA viral load) with medication, or has an active hepatitis B or C infection.
  • Has spinal cord compression or clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy.
  • Is lactating or pregnant as confirmed by pregnancy tests performed within 7 days before enrollment.
  • Has unresolved toxicities from previous anticancer therapy.
  • Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator.
  • Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients of DS-1062a.
  • Has any other medical conditions, including cardiac disease or psychological disorders, and/or substance abuse that would increase the safety risk to the participant or interfere with participation of the participant or evaluation of the clinical study in the opinion of the Investigator.
  • Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement, or prior pneumonectomy.

Locations

  • University of California, Los Angeles accepting new patients
    Los Angeles California 90095 United States
  • Next Oncology accepting new patients
    San Antonio Texas 78229 United States
  • START Oncology accepting new patients
    San Antonio Texas 78229 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Daiichi Sankyo Co., Ltd.
ID
NCT03401385
Phase
Phase 1
Study Type
Interventional
Last Updated