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A Phase 1B/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 (IDeate-PanTumor02)

A Study to Evaluate the Efficacy and Safety of Ifinatamab Deruxtecan (I-DXD) in Subjects with Recurrent or Metastatic Solid Tumors (IDeate-PanTumor02)

Inoguchi Akihiro

Daiichi Sankyo Co., Ltd.

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

dsclinicaltrial_jp@daiichisankyo.com

Contact for Clinical Trial Information

Daiichi Sankyo Co., Ltd.

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

+81-3-6225-1111

dsclinicaltrial_jp@daiichisankyo.com

Recruiting

May. 15, 2024

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Must have at least 1 lesion, not previously irradiated, amenable to core biopsy and must consent to provide a pretreatment biopsy tissue sample.
2. Ages >=18 years.
3. At least 1 measurable lesion on CT or MRI according to RECIST v1.1, as assessed by the investigator.
4. Documentation of radiological disease progression on or after the previous standard-of-care regimen in the advanced/metastatic setting.
5. Has an ECOG PS of 0 or 1.

for EC
1. Pathologically or cytologically documented EC of any histological carcinoma subtype or endometrial carcinosarcoma, irrespective of MSI or MMR status.
2. Relapse or progression after a platinum-containing systemic treatment and an ICI-containing regimen (combined or sequential). With actionable target tumor mutation should have been previously treated with targeted therapy, with a maximum of 3 prior lines of therapy for endometrial carcinoma or carcinosarcoma.

for HNSCC
1. 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.
2. Has disease progression after platinum-based and ICI treatment, whether administered in combination or separately. With actionable target tumor mutation should have been previously treated with targeted therapy, with a maximum of 2 prior therapy lines for unresectable or metastatic HNSCC.
3. Without radiographic evidence of major blood vessel invasion/infiltration or tumor demonstrating a >90-degree abutment or encasement of a major blood vessel.
4. 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.
5. Documented p16 status for oropharyngeal cancer.

for PDAC
1. 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 or after 2 lines of therapy if having actionable target tumor mutation and has been previously treated with targeted therapy. No prior treatment with topoisomerase I inhibitors, such as irinotecan or topotecan.

for CRC
1. Pathologically or cytologically documented unresectable or metastatic CRC with MSS status.
2. 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, or relapse or progression after 2 lines of therapy if having received targeted therapy.
3. No prior treatment with topoisomerase I inhibitors, such as irinotecan or topotecan.

for HCC
1. 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.
2. Relapse or progression after 1 prior line of an ICI-containing regimen (combination or monotherapy) in the locally advanced/metastatic setting, with a maximum of 2 prior lines. With actionable target tumor mutation should have been previously treated with targeted therapy.
3. BCLC Stage B or C.
4. Liver function status should be CP Class A.
5. ALBI Grade 1 within 7 days prior to the first dose of study drug.
6. 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
1. 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. With PD-(L)1+ or MSI-H/dMMR should receive ICI treatment if ICIs are standard of care in the country, unless the subject is ineligible for ICI treatment.
2. If having known history of HER2 positivity or actionable target, must have been previously treated with a targeted therapy.

for UC
1. 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.
2. Relapse or progression after at least 1 prior line of ICI-containing systemic therapy, and 1 prior line of systemic chemotherapy, given in combination with other anticancer therapy or separately, with a maximum of 3 prior therapy lines.

for CC
1. Histologically confirmed unresectable or metastatic CC that was previously treated with >=1 prior line of systemic therapy in the locally advanced or metastatic setting. With actionable target tumor mutation should have been previously treated with targeted therapy.

for OVC
1. 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 and bevacizumab unless the subject is ineligible for treatment with bevacizumab.
2. 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.
3. Not considered primary platinum refractory and has not progressed during platinum treatment or within 4 weeks after the completion of platinum treatment.
4. With actionable target tumor mutation should have been previously treated with targeted therapy.

for BTC
1. Pathologically or cytologically documented unresectable or metastatic BTC.
2. Relapse or progression after at least 1 prior line of systemic therapy, or 2 prior lines of systemic therapy if having an actionable target and received targeted therapy.
3. 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
1. Pathologically or cytologically documented unresectable or metastatic BC.
2. Low HER2 expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested), according to ASCO-CAP 2018 HER2 testing guidelines.
3. Progression on or after treatment with T-DXd.
4. Relapse or progression after at least 2 and a maximum of 3 prior lines of systemic therapy. 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. With actionable target tumor mutation should have been previously treated with targeted therapy.

for HER2 IHC 0 BC
1. Pathologically or cytologically documented unresectable or metastatic BC.
2. Negative for HER2 expression, defined as IHC 0 (ISH- or untested) according to ASCO-CAP 2018 HER2 testing guidelines.
3. Relapse or progression after at least 2 and a maximum of 3 prior lines of systemic therapy. 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. With actionable target tumor mutation should have been previously treated with targeted therapy.

for Cutaneous (Acral and Non-acral) Melanoma
1. Histologically or cytologically confirmed cutaneous (acral and non-acral) melanoma.
2. 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 having BRAF-mutated melanoma or other actionable target tumor mutation, they must have had disease progression on targeted therapy as well.

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 antibody drug conjugate (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.

Both

EC; HNSCC; PDAC; CRC; HCC ; Ad-eso/GEJ/Gastric; UC; OVC; CC; BTC; HER2-low BC; IHC 0 BC; melanoma

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

- 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.

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

Mar. 26, 2024

Yes

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