Informations générales (source: ClinicalTrials.gov)
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)
Interventional
Phase 2
Daiichi Sankyo (Voir sur ClinicalTrials)
avril 2024
juillet 2028
12 août 2025
This study is designed to assess the efficacy and safety of ifinatamab deruxtecan (I-DXD)
in the following tumor types: endometrial cancer (EC); head and neck squamous cell
carcinoma (HNSCC); pancreatic ductal adenocarcinoma (PDAC); colorectal cancer (CRC);
hepatocellular carcinoma (HCC); adenocarcinoma of esophagus, gastroesophageal junction,
and stomach (Ad-Eso/GEJ/gastric); urothelial carcinoma (UC); ovarian cancer (OVC);
cervical cancer (CC); biliary tract cancer (BTC); human epidermal growth factor 2
(HER2)-low breast cancer (BC); HER2 immunohistochemistry (IHC) 0 BC; and cutaneous
melanoma.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | Principal Investigator | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Principal Investigator | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Georges François Leclerc - 21079 - Dijon cedex - France | Principal Investigator | Contact (sur clinicalTrials) | |||
| Centre Léon Bérard - 69008 - Lyon - Rhone - France | Principal Investigator | Contact (sur clinicalTrials) | |||
| Chu Besançon - Hôpital Jean Minjoz - 25000 - Besancon - France | Principal Investigator | Contact (sur clinicalTrials) | |||
| Ico - Site René Gauducheau - 44800 - Saint Herblain - France | Principal Investigator | Contact (sur clinicalTrials) | |||
| Institut Bergonié - 33076 - Bordeaux cedex - France | Contact (sur clinicalTrials) | ||||
| Institut Claudius Regaud - 31059 - Toulouse - France | Principal Investigator | Contact (sur clinicalTrials) | |||
| Institut Régional Du Cancer de Montpellier - 34298 - Montpellier - France | Principal Investigator | Contact (sur clinicalTrials) | |||
Critères
Tous
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.
4. Inadequate treatment washout period before enrollment as specified in the protocol.
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.
4. Inadequate treatment washout period before enrollment as specified in the protocol.