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A Phase 2 Pan-tumor, Open-label Study to Evaluate the Efficacy and Safety of Ifinatamab Deruxtecan (I-DXd) in Subjects with Recurrent or Metastatic Solid Tumors

Pan-tumor Study of I-DXd in Subjects with Recurrent or Metastatic Solid Tumors

Inoguchi Akihiro

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

dsclinicaltrial@daiichisankyo.co.jp

Contact for Clinical Trial Information

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Pending

May. 15, 2024

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

Participants must meet all of the following criteria to be included in the study:
1. Sign and date the informed consent form prior to the start of any study-specific qualification procedures.
2. Participant must have at least 1 lesion, not previously irradiated, amenable to core biopsy and must consent to provide a pretreatment biopsy tissue sample. An archival tumor tissue sample obtained within 6 months of consent and after progression during/after treatment with the participant's most recent cancer therapy regimen is also acceptable.
3. Participants ages >=18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years).
4. At least 1 measurable lesion on computed tomography (CT) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), as assessed by the investigator.
5. Documentation of radiological disease progression on or after the previous regimen in the advanced/metastatic setting.
6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Has adequate organ function as specified in the protocol within 7 days before the start of study drug.
8. If the participant is a female of childbearing potential, she must have a negative serum pregnancy test during Screening (within 28 days before the first dose of I-DXd). Male and female participants 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 7 months for females and 4 months for males after the last dose of study drug.
9. Male participants must not freeze or donate sperm starting at enrollment and throughout the study period and for at least 4 months after the final study drug administration.
10. Female participants must not donate, or retrieve for their own use, ova from the time of enrollment, throughout the Study Treatment Period, and for at least 7 months after the final study drug administration.

Additional Inclusion Criteria for endometrial cancer (EC) Participants
11. Pathologically or cytologically documented EC of any histological carcinoma subtype or endometrial carcinosarcoma.
12. Relapse or progression after a platinum-containing systemic treatment and an immune checkpoint inhibitor (ICI)-containing regimen (combined or sequential) in the advanced/metastatic setting.

Additional Inclusion Criteria for head and neck squamous cell carcinoma (HNSCC) Participants
13. Pathologically or cytologically documented unresectable or metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx.
14. Has disease progression or intolerance post platinum-based and ICI treatment, whether administered in combination or separately, with a maximum of 2 prior therapy lines for unresectable or metastatic HNSCC.
15. Participants without tumors that invade major vessels (eg, the carotid) as shown unequivocally by imaging studies.
16. Participants with no prior history of Grade >=3 bleeding as per the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE) v5.0 within 28 days prior to the start of study drug related to the current head and neck cancer may be included in the study.
17. Documented human papillomavirus/p16 status for oropharyngeal cancer (historical results are acceptable if available).

Additional Inclusion Criteria for pancreatic ductal adenocarcinoma (PDAC) Participants
18. Pathologically or cytologically documented unresectable or metastatic pancreatic adenocarcinoma that has relapsed or progressed after 1 prior line of systemic therapy in the locally advanced/metastatic setting.

Additional Inclusion Criteria for colorectal cancer (CRC) Participants
19. Pathologically or cytologically documented unresectable or metastatic CRC with Microsatellite Stable (MSS) status.
20. Relapse or progression after 1 prior line of systemic therapy with or without a biologic agent.
21. No prior treatment with topoisomerase I inhibitors, such as irinotecan or topotecan.

Additional Inclusion Criteria for hepatocellular carcinoma (HCC) Participants
22. Pathologically or cytologically documented unresectable or metastatic HCC or noninvasive diagnosis of HCC as per the American Association for the Study of Liver Diseases (AASLD) criteria in subjects with a confirmed diagnosis of cirrhosis.
23. Relapse or progression after 1 prior line of an ICI-containing regimen (combination or monotherapy) in the locally advanced/metastatic setting.
24. Barcelona Clinic Liver Cancer (BCLC) Stage B or C.
25. Liver function status should be Child-Pugh (CP) Class A.
26. Participants with large esophageal varices at risk of bleeding must be treated with conventional medical intervention: beta blockers or endoscopic treatment.

Additional Inclusion Criteria for adenocarcinoma of esophagus, gastroesophageal junction, and stomach (Ad-Eso/GEJ/gastric) Participants
27. Pathologically or cytologically documented unresectable or metastatic Ad-eso/GEJ/Gastric that has relapsed or progressed after 1 prior line of systemic therapy in the locally advanced/metastatic setting.
28. If the participant has known history of HER2 positivity (defined by immunohistochemistry [IHC] 3+ or IHC 2+ and in situ hybridization positive [ISH+], as classified by American Society of Clinical Oncology - College of American Pathologists [ASCO CAP]), the subject must have been previously treated with a HER2-directed therapy.

Additional Inclusion Criteria for non-squamous non-small cell lung cancer (NSCLC) Participants
29. Pathologically or cytologically documented unresectable or metastatic non-squamous NSCLC that has relapsed or progressed after 1 or more prior line of systemic therapy in the locally advanced/metastatic setting.
30. Participant is not eligible for actionable genomic alteration-directed therapy.

Additional Inclusion Criteria for urothelial carcinoma (UC) Participants
31. Pathologically or cytologically documented unresectable or metastatic UC.
32. Relapse or progression after 1 prior line of an ICI-containing systemic therapy, whether administered in combination or sequentially to chemotherapy in advanced/metastatic settings.

Participants who meet any of the following criteria will be disqualified from entering the study:
1. Prior treatment with orlotamab, enoblituzumab, or other B7-homologue 3 (B7-H3)-targeted agents.
2. Prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities.
3. Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
4. Inadequate treatment washout period before enrollment as specified in the protocol.
5. Any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
6. Clinically significant corneal disease.
7. Uncontrolled or significant cardiovascular disease.
8. History of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening.
9. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc) and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc), prior pneumonectomy, or requirement for supplemental oxygen.
10. Participants who require chronic steroid treatment at enrollment (dose of 10 mg daily or more prednisone equivalent), except for low-dose inhaled steroids (for asthma/COPD) or topical steroids (for mild skin conditions), or intra-articular steroid injections.
11. History of malignancy within the 3 years prior to enrollment, except adequately resected nonmelanoma skin cancer, curatively treated in situ disease, superficial gastrointestinal tract tumors, and non-muscle invasive bladder cancer curatively resected by endoscopic surgery.
12. History of allogeneic bone marrow, stem cell, or solid organ transplant.
13. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v5.0 Grade <=1 or baseline.
14. History of hypersensitivity to the drug substances, inactive ingredients in the drug product, or severe hypersensitivity reactions to other monoclonal antibodies.
15. Has evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
16. Known human immunodeficiency virus (HIV) infection that is not well controlled.
17. Has active or uncontrolled hepatitis B or C infection.
18. Has an active, known, or suspected autoimmune disease.
19. Any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses, psychiatric illness/social situations, and substance abuse) or other factors that, in the investigator's opinion, make it undesirable for the subject to participate in the study or would jeopardize compliance with the protocol.
20. Has received a live vaccine within 30 days prior to the first dose of study drug.
21. Is pregnant, breastfeeding, or planning to become pregnant.
22. Has prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant; alter the absorption, distribution, metabolism, or excretion of the study drug; or confound the assessment of study results.

Both

EC; HNSCC; PDAC; CRC; HCC ; Ad-eso/GEJ/Gastric; Non-squamous NSCLC; UC

I-DXd is administered intravenously on Day 1 of each 21-day cycle at 12 mg/kg

ORR by RECIST v1.1

Objective Response Rate (ORR) as Assessed by Investigator
ORR is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) as assessed by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Safety (DLT: HCC Cohort, TEAE, SAE, AESI, etc.), DCR (disease control rate), DoR (duration of response), PFS (progression-free survival), OS (overall survival), PK (pharmacokinetic(s)), Immunogenicity

Yes

De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/ Supporting Information: -Study Protocol -Statistical Analysis Plan (SAP) -Informed Consent Form (ICF) Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication. Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent. URL: https://vivli.org/ourmember/daiichi-sankyo/

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