First-in-human Study of DS-1062a for Advanced Solid Tumors (TROPION-PanTumor01)

• Status: Recruiting
• Trial end date: 2024-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Daiichi Sankyo Co., Ltd.
• Collaborators: AstraZeneca; Daiichi Sankyo, Inc.

Criteria

Inclusion Criteria

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 1.

• 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.

Exclusion Criteria:

• 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.