A Study to Evaluate the Efficacy and Safety of Ifinatamab Deruxtecan (I-DXD) in Subjects with Recurrent or Metastatic Solid Tumors (IDeate-Pantumor02)

JRCT ID: jRCT2031240016

Registered date:05/04/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: EC; HNSCC; PDAC; CRC; HCC ; Ad-eso/GEJ/Gastric; UC; OVC; CC; BTC; HER2-low BC; IHC 0 BC; melanoma
• Date of first enrollment: 06/06/2024
• Target sample size: 520
• Countries of recruitment: United States,Japan,Australia,Japan,Belgium,Japan,France,Japan,Italy,Japan,Korea,Japan,Spain,Japan,Taiwan,Japan,Argentina,Japan,Brazil,Japan,Chile,Japan,Germany,Japan,Iran,Japan,Ireland,Japan,Mexico,Japan,Poland,Japan,Portugal,Japan,Turkey,Japan,Netherlands,Japan
• Study type: Interventional
• Intervention(s): I-DXd is administered intravenously on Day 1 of each 21-day cycle at 12 mg/kg

Outcome(s)

Primary Outcome

- 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.

- Number of Participants Reporting Dose-limiting Toxicities in the HCC Cohort
- A dose-limiting toxicity (DLT) is defined as any treatment-emergent adverse event (TEAE) not attributable to disease or disease-related processes that occurs during the DLT evaluation period (from C1D1 to the end of Cycle 1 in Safety Run-in) and is Grade 3 or above, according to NCI-CTCAE version 5.0.

- Number of Participants Reporting Treatment-emergent Adverse Events and Death in the HCC Cohort
- A TEAE is defined as an adverse event (AE) with a start or worsening date during the on-treatment period. AEs will be coded using MedDRA and will be graded using NCI-CTCAE v5.0.

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

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

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.
3. Participants ages >=18 years.
4. At least 1 measurable lesion on CT or MRI according to RECIST v1.1, as assessed by the investigator.
5. Documentation of radiological disease progression on or after the previous standard-of-care regimen in the advanced/metastatic setting.
6. Has an ECOG PS of 0 or 1.
7. Has adequate organ function as specified in the protocol.
8. If the participant is a female of childbearing potential, she must have a negative serum pregnancy test during Screening.
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.

for EC Participants
11. Pathologically or cytologically documented EC of any histological carcinoma subtype or endometrial carcinosarcoma, irrespective of MSI or MMR status.
12. Relapse or progression after a platinum-containing systemic treatment and an ICI-containing regimen (combined or sequential), with a maximum of 3 prior lines of therapy for endometrial carcinoma or carcinosarcoma.

for HNSCC Participants
13. Pathologically or cytologically documented unresectable or metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx, excluding nasopharynx, nasal cavity and paranasal sinuses, and unknown primary.
14. Has disease progression after 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 radiographic evidence of major blood vessel invasion/infiltration or tumor demonstrating a >90-degree abutment or encasement of a major blood vessel.
16. Participants with no prior history of Grade >=3 bleeding as per the 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 p16 status for oropharyngeal cancer.

for PDAC Participants
18. Pathologically or cytologically documented unresectable or metastatic pancreatic adenocarcinoma that has relapsed or progressed after 1 prior line of gemcitabine-based systemic therapy in the locally advanced/metastatic setting.

for CRC Participants
19. Pathologically or cytologically documented unresectable or metastatic CRC with MSS status.
20. Relapse or progression after 1 prior line of systemic therapy including a fluoropyrimidine plus oxaliplatin with or without Anti-VEGF mAb or anti-epidermal growth factor receptor mAb therapy, as clinically indicated.
21. No prior treatment with topoisomerase I inhibitors, such as irinotecan or topotecan.

for HCC Participants
22. Pathologically or cytologically documented unresectable or metastatic HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible) or noninvasive diagnosis of HCC as per the 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 Stage B or C.
25. Liver function status should be Child-Pugh Class A.
26. Albumin-Bilirubin Grade 1 within 7 days prior to the first dose of study drug.
27. Participants with large esophageal varices at risk of bleeding must be treated with conventional medical intervention: beta blockers or endoscopic treatment.

for Ad-eso/GEJ/Gastric Participants
28. 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.
29. If the participant has known history of HER2 positivity, the subject must have been previously treated with a HER2.

for UC Participants
30. Pathologically or cytologically documented unresectable or metastatic UC of the bladder, renal pelvis, ureter, or urethra. Participants with histological variants are allowed if urothelial histology is predominant. Small cell/neuroendocrine tumors are not allowed even if mixed histology.
31. Relapse or progression after at least 1 prior line of ICI-containing systemic therapy, whether administered in combination or sequentially to another anticancer treatment, with a maximum of 3 prior therapy lines.

for CC Participants
32. Histologically confirmed unresectable or metastatic CC that was previously treated with >=1 prior line of systemic therapy in the locally advanced or metastatic setting.

for OVC Participants
33. Histologically confirmed high-grade serous OVC, high-grade endometrioid OVC, primary peritoneal cancer, or fallopian tube cancer that was previously treated with at least 1 line of platinum-based therapy.
34. Participant is no longer considered eligible for platinum-based therapy per the investigator's opinion or has progressed less than 180 days after the last dose of platinum therapy.
35. Participant is not considered primary platinum refractory and has not progressed during platinum treatment or within 4 weeks after the completion of platinum treatment.

for BTC Participants
36. Pathologically or cytologically documented unresectable or metastatic BTC (intra- or extrahepatic cholangiocarcinoma or gallbladder carcinoma).
37. Relapse or progression after at least 1 prior line of systemic therapy, or 2 prior lines of systemic therapy if the participant has an actionable target and has received targeted therapy.
38. Histological subtypes other than ampullary cancer, small cell cancer, lymphoma, sarcoma, neuroendocrine tumors, mixed tumor histology, and/or mucinous cystic neoplasms.

for HER2-Low BC Participants
39. Pathologically or cytologically documented unresectable or metastatic BC.
40. Low HER2 expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested), according to ASCO-CAP 2018 HER2 testing guidelines.
41. Progression on or after treatment with T-DXd.
42. Relapse or progression after at least 2 and a maximum of 3 prior lines of systemic therapy. Subjects with metastatic HR+ BC who have received endocrine-based therapy and have received at least 2 and a maximum of 3 prior lines of additional systemic therapy in the metastatic setting.

for HER2 IHC 0 BC Participants
43. Pathologically or cytologically documented unresectable or metastatic BC.
44. Negative for HER2 expression, defined as IHC 0 (ISH- or untested) according to ASCO-CAP 2018 HER2 testing guidelines.
45. Relapse or progression after at least 2 and a maximum of 3 prior lines of systemic therapy. Participants with metastatic HR+ BC who have received endocrine-based therapy and have received at least 2 and a maximum of 3 prior lines of additional systemic therapy in the metastatic setting.

for Cutaneous (Acral and Non-acral) Melanoma Subjects
46. Histologically or cytologically confirmed cutaneous (acral and non-acral) melanoma.
47. Disease progression while on or after having received treatment with >=1 prior line of ICI-based therapy. Prior anti-PD-(L)1 therapy in the adjuvant setting may be counted as 1 line if there is recurrence within 12 weeks of the last dose. If the participant had proto-oncogene BRAF-mutated melanoma, they must have had disease progression on BRAF/MEK inhibitor therapy as well.

Exclude criteria

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, including I-DXd.
2. Prior discontinuation of an ADC that consists of an exatecan derivative (eg, T-DXd) 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 mAbs.
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.

Related Information

• Primary Sponsor: Inoguchi Akihiro
• Secondary Sponsor: Merck Sharp & Dohme LLC
• Secondary ID(s): NCT06330064,2023-509632-26