Trial: A Study To Evaluate The Efficacy And Sa…

Trial Details

Sponsor: Daiichi Sankyo (industry)

Phase: 2

Start date: April 10, 2024

Planned enrollment: 520

Trial ID: NCT06330064

More trial details at ClinicalTrials.gov

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: Ifinatamab deruxtecan (MK-2400, DS-7300, I-DXd)

HealthScout AI Analysis

Goal: The trial aims to assess the efficacy and safety of ifinatamab deruxtecan (I-DXd), a B7-H3-directed antibody-drug conjugate, across a range of recurrent or metastatic solid tumors that have progressed following standard systemic therapies.

Patients: Patients enrolled are adults (≥18 years) with recurrent or metastatic solid tumors, including endometrial cancer, head and neck squamous cell carcinoma, pancreatic ductal adenocarcinoma, colorectal cancer, hepatocellular carcinoma, esophageal/gastric adenocarcinoma, urothelial carcinoma, ovarian cancer, cervical cancer, biliary tract cancer, HER2-low and HER2-IHC 0 breast cancer, and cutaneous melanoma. Eligible patients must have measurable disease, ECOG 0-1, documented progression after at least one prior line of standard therapy (with more specific requirements by tumor type), and accessible tumor for biopsy. Patients previously treated with B7-H3 targeted agents, with certain comorbidities, or with active brain metastases are excluded.

Design: This is a non-randomized, open-label, multi-cohort phase 1b/2 study. Each tumor-type cohort initiates with a safety and efficacy assessment (Stage 1) and, if criteria are met, may expand to Stage 2. The hepatocellular carcinoma cohort includes a dedicated safety run-in phase.

Treatments: All participants receive ifinatamab deruxtecan intravenously (12 mg/kg, or dose as determined for HCC) every three weeks. Ifinatamab deruxtecan is an investigational antibody-drug conjugate targeting B7-H3 (CD276), a protein broadly expressed in solid tumors. The drug comprises a humanized anti-B7-H3 monoclonal antibody conjugated to a topoisomerase I inhibitor payload via a cleavable linker. Clinical results to date, particularly in small cell lung cancer, have demonstrated promising efficacy with objective response rates exceeding 50% at the 12 mg/kg dose, median progression-free survival of 5 to 6 months, and an acceptable safety profile. Principal toxicities include gastrointestinal and hematologic adverse events, with interstitial lung disease reported in a minority of patients.

Outcomes: Primary endpoints include objective response rate by RECIST v1.1 in all cohorts, and dose-limiting toxicities for the HCC cohort. Additional efficacy endpoints include duration of response, progression-free survival, disease control rate, and overall survival. Safety is assessed by the incidence of treatment-emergent adverse events, serious adverse events, and adverse events of special interest. Pharmacokinetics (PK) of I-DXd and anti-drug antibody (ADA) development are also evaluated.

Burden on patient: Patient burden is anticipated to be moderate to high. Baseline and on-study tumor biopsies are required for all patients, and PK sampling is frequent, especially during the first three cycles (including pre-dose, end of infusion, and multiple timepoints post-infusion). Regular imaging is mandated per RECIST, and safety labs are performed routinely. The intravenous dosing requires travel every three weeks. The trial’s requirements for fresh biopsies and intensive PK/ADA assessments, particularly early in enrollment, increase the complexity and intensity beyond standard therapy or later-phase registration trials.

Eligibility

Show Criteria

Participants must meet all of the following criteria to be included in the study:

Common Inclusion Criteria for All Participants

1. 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.

2. Participants ages ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is \>18 years).

3. 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.

4. Documentation of radiological disease progression on or after the previous standard-of-care regimen in the advanced/metastatic setting.

5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Additional Inclusion Criteria for EC Participants

1. Pathologically or cytologically documented EC of any histological carcinoma subtype or endometrial carcinosarcoma, irrespective of microsatellite instability or mismatch repair status.

2. Relapse or progression after a platinum-containing systemic treatment and an immune checkpoint inhibitor (ICI)-containing regimen (combined or sequential). Subjects 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. Neoadjuvant/adjuvant therapy may count as 1 line of therapy if the subject progressed within 6 months after completion of therapy.

Additional Inclusion Criteria for HNSCC Participants

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. Subjects 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. Participants without radiographic evidence of major blood vessel invasion/infiltration or tumor demonstrating a \>90-degree abutment or encasement of a major blood vessel.

4. Participants with no prior history of Grade ≥3 bleeding as per the National Cancer Institute Common Terminology Criteria for Adverse Events (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 (historical results are acceptable if available).

Additional Inclusion Criterion for PDAC Participants

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 the subject has actionable target tumor mutation and has been previously treated with targeted therapy. No prior treatment with topoisomerase I inhibitors, such as irinotecan or topotecan.

Additional Inclusion Criteria for CRC Participants

1. Pathologically or cytologically documented unresectable or metastatic CRC with microsatellite stable status.

2. Relapse or progression after 1 prior line of systemic therapy including a fluoropyrimidine plus oxaliplatin with or without anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb) or anti-epidermal growth factor receptor mAb therapy, as clinically indicated, or relapse or progression after 2 lines of therapy if the subject has received targeted therapy.

Note: Prior adjuvant/neoadjuvant systemic cytotoxic chemotherapy will count as 1 line of prior systemic therapy if there is documented disease progression during therapy or within 6 months of chemotherapy completion.

3. No prior treatment with topoisomerase I inhibitors, such as irinotecan or topotecan.

Additional Inclusion Criteria for HCC Participants

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 American Association for the Study of Liver Diseases (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. Subjects with actionable target tumor mutation should have been previously treated with targeted therapy.

3. Barcelona Clinic Liver Cancer (BCLC) Stage B or C.

4. Liver function status should be Child-Pugh (CP) Class A.

5. Albumin-Bilirubin (ALBI) Grade 1 within 7 days prior to the first dose of study drug.

6. 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 Ad-eso/GEJ/Gastric Participants

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. Subjects 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 the participant has known history of HER2 positivity (defined by IHC 3+ or IHC 2+ and in situ hybridization \[ISH\] positive, as classified by American Society of Clinical Oncology - College of American Pathologists \[ASCO CAP\]) or actionable target, the subject must have been previously treated with a targeted therapy.

Additional Inclusion Criteria for UC Participants

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.

1. At least 1 line of therapy should include enfortumab vedotin in countries where enfortumab vedotin is approved and available.

2. Perioperative systemic therapies will be counted as 1 line of therapy.

3. To meet inclusion criteria requirement of prior ICI-containing therapy, use in the perioperative or metastatic setting will suffice.

4. Subjects with actionable target tumor mutation should have been previously treated with targeted therapy.

5. The same regimen administered twice in different disease settings will be counted as 1 line of prior therapy.

Additional Inclusion Criteria for CC Participants

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. Subjects with actionable target tumor mutation should have been previously treated with targeted therapy.

2. Participants should receive prior anti-programmed death 1/programmed death-ligand 1 treatment and/or tisotumab vedotin if those are standard of care in the country, unless the subject is ineligible for these treatments.

Additional Inclusion Criteria for OVC Participants

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. 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.

3. Participant is not considered primary platinum refractory and has not progressed during platinum treatment or within 4 weeks after the completion of platinum treatment.

4. Subjects with actionable target tumor mutation should have been previously treated with targeted therapy.

Additional Inclusion Criteria for BTC Participants

1. Pathologically or cytologically documented unresectable or metastatic BTC (intra- or extrahepatic cholangiocarcinoma or gallbladder carcinoma).

2. 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.

3. Histological subtypes other than ampullary cancer, small cell cancer, lymphoma, sarcoma, neuroendocrine tumors, mixed tumor histology, and/or mucinous cystic neoplasms (Please note that the histological subtypes listed here are not allowed.)

Additional Inclusion Criteria for HER2-Low BC Participants

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, based on most recent testing, regardless of hormonal status.

3. Progression on or after treatment with trastuzumab deruxtecan (T-DXd).

4. Relapse or progression after at least 2 and a maximum of 3 prior lines of systemic therapy. Subjects with metastatic hormone receptor (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. Subjects with actionable target tumor mutation should have been previously treated with targeted therapy.

Additional Inclusion Criteria for HER2 IHC 0 BC Participants

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, based on the most recent testing, regardless of hormonal status.

3. 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. Subjects with actionable target tumor mutation should have been previously treated with targeted therapy.

Additional Inclusion Criteria for Cutaneous (Acral and Non-acral) Melanoma Subjects

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 the subject had 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.

Wenatchee, Washington, 98801, United States

No email / No phone

Status: Recruiting

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)

Trial Details

Show Summary from Sponsor

More details:

Investigational Drug AI Analysis

Show for: Ifinatamab deruxtecan (MK-2400, DS-7300, I-DXd)

Overview

Mechanism of Action

Efficacy

Safety

Further Reading

HealthScout AI Analysis

Eligibility

Show Criteria

Sites (114)

Hospital Aleman

Hospital Sirio Libanes

Centro de Investigaciones Medicas Mar Del Plata

DIABAID

Genesiscare North Shore Oncology

St Vincent'S Hospital Sydney

St John of God Subiaco Hospital

Princess Alexandra Hospital

Uz Leuven

Universitair Ziekenhuis Gent

Grand Hospital de Charleroi

Cliniques Universitaires Saint-Luc

Chu de Liă Ge

Hospital de Clă Nicas de Porto Alegre

Cepon - Centro de Pesquisas Oncolă"Gicas de Santa Catarina

Hospital de Câncer de Barretos - Fundação Pio XII

Hospital São Lucas Da Pucrs

Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho

James Lind Centro de Investigacion Del Cancer

Biocenter

Ic La Serena Research

Centro Del Cancer UC

Clinica Redsalud Vitacura

Centre Léon Bérard

Ico - Site René Gauducheau

Institut Claudius Regaud

Institut Gustave Roussy

Institut Curie - Site de Paris

Chu Besançon - Hôpital Jean Minjoz

Institut Bergonié

Centre Georges François Leclerc

Institut Régional Du Cancer de Montpellier

Universitaetsklinikum Leipzig Aoer

Universitaetsmedizin Der Johannes Gutenberg-Universitaet Mainz

Universitaetsklinikum Muenster

Charită - Campus Charită Mitte

Vivantes Klinikum Neukoelln

Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt

Universitaetsklinikum Heidelberg

Slk-Kliniken Heilbronn Gmbh

Cork University Hospital

Mater Misericordiae University Hospital

Tallaght Hospital

St Vincent'S University Hospital

University Hospital Galway

Fondazione Del Piemonte Per L'Oncologia Irccs Candiolo

Istituto Clinico Humanitas

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Istituto Nazionale Tumori Fondazione G. Pascale

Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)

Fondazione Irccs Istituto Nazionale Dei Tumori

Kindai University Hospital

Shizuoka Cancer Center

National Hospital Organization Shikoku Cancer Center

The Cancer Institute Hospital of Jfcr

National Cancer Center Hospital East

National Cancer Center Hospital

Saitama Cancer Center

Aichi Cancer Center Hospital

Medical Care & Research Sa de Cv

Cryptex Investigacion Clinica S.A. de C.V.

Centro de Atenciă"N E Investigaciă"N Clă Nica En Oncologă A

Umc Utrecht

Amsterdam Umc, Locatie Vumc

Universitair Medisch Centrum Groningen