Informations générales (source: ClinicalTrials.gov)
An Open-label, Dose Escalation, Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-676 as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Advanced or Metastatic Solid Tumors (iintune-1)
Interventional
Phase 1/Phase 2
Takeda (Voir sur ClinicalTrials)
juillet 2020
janvier 2026
26 avril 2025
The main aim of this study is to check if people with advanced solid tumors have side
effects from dazostinag, and to check how much dazostinag they can receive without
getting significant side effects from it when given alone and in combination with
pembrolizumab. The study will be conducted in two phases including a dose escalation
phase and a dose expansion phase. In the dose escalation phase, escalating doses of
dazostinag are being tested alone and in combination with pembrolizumab to treat
participants who have advanced or metastatic solid tumors. In the dose expansion phase,
dazostinag will be studied with pembrolizumab with or without chemotherapy in
participants with untreated metastatic or recurrent, unresectable squamous cell carcinoma
of head and neck (SCCHN) and in combination with pembrolizumab in third-line or later
recurrent locally advanced or metastatic microsatellite instability-high/mismatch repair
deficient (MSI-H/dMMR) and third-line recurrent locally advanced or metastatic
microsatellite stable/mismatch repair proficient (MSS/pMMR) colorectal cancer (CRC).
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Caroline EVEN | 20/06/2024 12:50:18 | Contacter | ||
| HOPITAL FOCH | Jaafar BENNOUNA | 05/05/2025 07:12:07 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Saint Antoine | 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 de Lutte contre le Cancer - Centre Oscar Lambret - 59000 - Lille - France | Contact (sur clinicalTrials) | ||||
| Centre Georges Francois Leclerc - 21079 - Dijon - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Regional et Universitaire de Besancon - Hopital Jean-Minjoz - 25000 - Besancon - France | Contact (sur clinicalTrials) | ||||
| Centre Leon Berard - 69008 - Lyon - France | Contact (sur clinicalTrials) | ||||
| Hopital de la Timone - 13385 - Marseille - France | Contact (sur clinicalTrials) | ||||
| Hopital Saint-Andre - 33000 - Bordeaux - France | Contact (sur clinicalTrials) | ||||
| Institut de Cancerologie de lOuest - Saint-Herblain - Site Rene Gauducheau - 44805 - St Herblain - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
2. Dazostinag SA (dose escalation Part 1A):
o With histologically confirmed (cytological diagnosis is acceptable) advanced or
metastatic solid tumors that have no standard therapeutic options or are intolerant
to these therapies.
3. Dazostinag in combination with pembrolizumab (dose escalation Parts 1B and Japan
safety lead-in):
- With histologically confirmed (cytological diagnosis is acceptable) advanced or
metastatic solid tumors that have no standard therapeutic options or are
intolerant to them, including:
- Tumors that have relapsed or are refractory to anti-programmed cell death
ligand protein 1 (anti PD-(L)-1) therapy.
- Tumors that are naive to anti-PD-(L)-1 therapy.
4. For expansion phase only:
- SCCHN (Part 2):
- Participants with histologically confirmed (cytological diagnosis is
acceptable) metastatic or recurrent, unresectable SCCHN that is considered
incurable by local therapies. Participants should not have had prior systemic
therapy administered in the recurrent or metastatic setting. Systemic therapy
which was completed more than 6 months before signing consent if given as part
of multimodal treatment of locally advanced disease is allowed.
- Anatomic subsites to be included are oral cavity, oropharynx, hypopharynx,
larynx, nasal cavity, and paranasal sinuses (maxillary, ethmoid, sphenoid, and
frontal). The exception to this is nasopharyngeal cancer and salivary gland
tumors, which will not be included.
- Participants with oropharyngeal cancer or tumors arising in the paranasal
sinuses (maxillary, ethmoid, sphenoid, and frontal) must agree to provide
archival tissue for human papilloma virus (HPV) testing or if known, HPV
testing results (using CINtec® p16 Histology assay is preferred but not
required) and a 70% cutoff point must be provided. Alternatively, archival
tissue or a fresh excisional or core needle biopsy (≥ 2 cores) is required for
the determination of HPV status. If HPV status was previously tested using this
method (CINtec® p16 Histology assay is preferred but not required), no
additional testing is required. Archival tissue can be obtained up to 90 days
prior to screening. Samples that are older than 90 days at screening may be
used after consultation with the sponsor.
- For Part 2A, tumors must have a PD-L1 CPS ≥ 1. Participants must agree to
provide fresh tumor biopsy for analysis from a core or excisional biopsy (fine
needle aspirate is not sufficient) at screening for PD-L1 CPS assessment by a
central laboratory. This specimen may be the diagnostic sample for participants
with a new diagnosis of metastatic SCCHN. Participants for whom newly obtained
samples cannot be obtained (eg, inaccessible or participant safety concern) may
submit an archived specimen only upon agreement from the Sponsor. Archival
tissue can be obtained up to 90 days prior to screening provided there was no
other treatment from the time of biopsy until the start of study treatment. For
Part 2B, any CPS is eligible but fresh or archival tissue is required for
confirmation of CPS status. Collection of the tissue samples for PD-L1
assessments for Part 2B can be discontinued by the sponsor if sufficient data
has been collected or dazostinag activity does not justify further collection.
- For Part 2B, participants must be eligible to receive treatment with either
cisplatin or carboplatin in combination with 5-fluorouracil (5-FU) per the
treating physician.
5. CRC (Part 3):
- Third-line or later MSI-H/dMMR CRC (Part 3A): Participants with histologically
confirmed (cytological diagnosis is acceptable) recurrent locally advanced or
metastatic MSI-H/dMMR CRC whose disease has progressed on or following therapy
with 1) an anti-PD-1 or PD-L1 antibody (i.e., pembrolizumab) and 2) at least
one line of combination chemotherapy including a fluoropyrimidine and
irinotecan OR oxaliplatin with or without an anti-epidermal growth factor
receptor (EGFR) or anti-vascular endothelial growth factor (VEGFR) monoclonal
antibody (i.e., cetuximab or bevacizumab). MSI-H/dMMR CRC participants must
have received at least 6 weeks of prior treatment with an anti-PD-(L)-1
antibody. Only one line of anti-PD-(L)-1 is permitted.
- Third-line MSS/pMMR CRC (Part 3B): Participants with histologically confirmed
(cytological diagnosis is acceptable) recurrent locally advanced or metastatic
MSS/pMMR CRC whose disease has progressed on or following therapy with 2
different lines of combination chemotherapy, including therapy with a
fluoropyrimidine and irinotecan AND therapy with a fluoropyrimidine and
oxaliplatin. Both lines of therapy may be given with or without an anti-EGFR or
anti-VEGFR monoclonal antibody (i.e., cetuximab or bevacizumab).
Participants with MSS/pMMR CRC must have progressed on or after combination
chemotherapy regimens containing BOTH irinotecan AND oxaliplatin.
- Participants with MSI-H/dMMR or MSS/pMMR CRC must have documented MSI/MMR
status assessed by a Clinical Laboratory Improvements Amendment-certified
(United States [US] sites or an accredited (outside of the US) local laboratory
using immunohistochemistry (IHC) and/or polymerase chain reaction (PCR) or next
generation sequencing (NGS) assay.
- Adequate tumor tissue available for central laboratory confirmation of MSI/MMR
status. Note: confirmation of central test positivity is not required before
treatment.
- Participants with MSI-H/dMMR or MSS/pMMR CRC must have been treated with 2
prior lines of therapy in the recurrent locally advanced or metastatic setting.
6. Adequate bone marrow, renal, hepatic and cardiac functions.
7. Left ventricular ejection fraction (LVEF) > 50%, as measured by echocardiogram or
multiple-gated acquisition (MUGA) scan within 4 weeks before receiving the first
dose of study drug.
8. Clinically significant toxic effects of previous therapy have recovered to Grade 1
(per NCI CTCAE Version 5.0) or baseline, except for alopecia, Grade 2 peripheral
neuropathy, and/or autoimmune endocrinopathies with stable endocrine replacement
therapy.
9. In dose escalation Part 1, (not applicable for the Japan safety lead-in) once
peripheral evidence of dazostinag pharmacodynamic stimulation of the innate and/or
adaptive immune system is observed in the blood and/or an imaging response/partial
response (CR/PR) is observed in at least 1 participant, subsequent participants
must:
- Have at least 1 lesion amenable for biopsy.
- Agree to have 2 tumor biopsies: 1 during the screening period and 1 while on
dazostinag treatment.
10. Must have at least 1 RECIST version 1.1-evaluable (measurable) lesion. For the dose
escalation phase (Part 1) only, nonmeasurable only disease is acceptable.
11. Pharmacokinetic (PK)/pharmacodynamic blood must be drawn on a peripherally-inserted
catheter. Dazostinag is preferentially administered through a central line, but
peripheral infusion is acceptable. If a peripheral line is used for dazostinag
and/or pembrolizumab infusion, it must be separate than the one used for
PK/pharmacodynamic collection.
1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
2. Dazostinag SA (dose escalation Part 1A):
o With histologically confirmed (cytological diagnosis is acceptable) advanced or
metastatic solid tumors that have no standard therapeutic options or are intolerant
to these therapies.
3. Dazostinag in combination with pembrolizumab (dose escalation Parts 1B and Japan
safety lead-in):
- With histologically confirmed (cytological diagnosis is acceptable) advanced or
metastatic solid tumors that have no standard therapeutic options or are
intolerant to them, including:
- Tumors that have relapsed or are refractory to anti-programmed cell death
ligand protein 1 (anti PD-(L)-1) therapy.
- Tumors that are naive to anti-PD-(L)-1 therapy.
4. For expansion phase only:
- SCCHN (Part 2):
- Participants with histologically confirmed (cytological diagnosis is
acceptable) metastatic or recurrent, unresectable SCCHN that is considered
incurable by local therapies. Participants should not have had prior systemic
therapy administered in the recurrent or metastatic setting. Systemic therapy
which was completed more than 6 months before signing consent if given as part
of multimodal treatment of locally advanced disease is allowed.
- Anatomic subsites to be included are oral cavity, oropharynx, hypopharynx,
larynx, nasal cavity, and paranasal sinuses (maxillary, ethmoid, sphenoid, and
frontal). The exception to this is nasopharyngeal cancer and salivary gland
tumors, which will not be included.
- Participants with oropharyngeal cancer or tumors arising in the paranasal
sinuses (maxillary, ethmoid, sphenoid, and frontal) must agree to provide
archival tissue for human papilloma virus (HPV) testing or if known, HPV
testing results (using CINtec® p16 Histology assay is preferred but not
required) and a 70% cutoff point must be provided. Alternatively, archival
tissue or a fresh excisional or core needle biopsy (≥ 2 cores) is required for
the determination of HPV status. If HPV status was previously tested using this
method (CINtec® p16 Histology assay is preferred but not required), no
additional testing is required. Archival tissue can be obtained up to 90 days
prior to screening. Samples that are older than 90 days at screening may be
used after consultation with the sponsor.
- For Part 2A, tumors must have a PD-L1 CPS ≥ 1. Participants must agree to
provide fresh tumor biopsy for analysis from a core or excisional biopsy (fine
needle aspirate is not sufficient) at screening for PD-L1 CPS assessment by a
central laboratory. This specimen may be the diagnostic sample for participants
with a new diagnosis of metastatic SCCHN. Participants for whom newly obtained
samples cannot be obtained (eg, inaccessible or participant safety concern) may
submit an archived specimen only upon agreement from the Sponsor. Archival
tissue can be obtained up to 90 days prior to screening provided there was no
other treatment from the time of biopsy until the start of study treatment. For
Part 2B, any CPS is eligible but fresh or archival tissue is required for
confirmation of CPS status. Collection of the tissue samples for PD-L1
assessments for Part 2B can be discontinued by the sponsor if sufficient data
has been collected or dazostinag activity does not justify further collection.
- For Part 2B, participants must be eligible to receive treatment with either
cisplatin or carboplatin in combination with 5-fluorouracil (5-FU) per the
treating physician.
5. CRC (Part 3):
- Third-line or later MSI-H/dMMR CRC (Part 3A): Participants with histologically
confirmed (cytological diagnosis is acceptable) recurrent locally advanced or
metastatic MSI-H/dMMR CRC whose disease has progressed on or following therapy
with 1) an anti-PD-1 or PD-L1 antibody (i.e., pembrolizumab) and 2) at least
one line of combination chemotherapy including a fluoropyrimidine and
irinotecan OR oxaliplatin with or without an anti-epidermal growth factor
receptor (EGFR) or anti-vascular endothelial growth factor (VEGFR) monoclonal
antibody (i.e., cetuximab or bevacizumab). MSI-H/dMMR CRC participants must
have received at least 6 weeks of prior treatment with an anti-PD-(L)-1
antibody. Only one line of anti-PD-(L)-1 is permitted.
- Third-line MSS/pMMR CRC (Part 3B): Participants with histologically confirmed
(cytological diagnosis is acceptable) recurrent locally advanced or metastatic
MSS/pMMR CRC whose disease has progressed on or following therapy with 2
different lines of combination chemotherapy, including therapy with a
fluoropyrimidine and irinotecan AND therapy with a fluoropyrimidine and
oxaliplatin. Both lines of therapy may be given with or without an anti-EGFR or
anti-VEGFR monoclonal antibody (i.e., cetuximab or bevacizumab).
Participants with MSS/pMMR CRC must have progressed on or after combination
chemotherapy regimens containing BOTH irinotecan AND oxaliplatin.
- Participants with MSI-H/dMMR or MSS/pMMR CRC must have documented MSI/MMR
status assessed by a Clinical Laboratory Improvements Amendment-certified
(United States [US] sites or an accredited (outside of the US) local laboratory
using immunohistochemistry (IHC) and/or polymerase chain reaction (PCR) or next
generation sequencing (NGS) assay.
- Adequate tumor tissue available for central laboratory confirmation of MSI/MMR
status. Note: confirmation of central test positivity is not required before
treatment.
- Participants with MSI-H/dMMR or MSS/pMMR CRC must have been treated with 2
prior lines of therapy in the recurrent locally advanced or metastatic setting.
6. Adequate bone marrow, renal, hepatic and cardiac functions.
7. Left ventricular ejection fraction (LVEF) > 50%, as measured by echocardiogram or
multiple-gated acquisition (MUGA) scan within 4 weeks before receiving the first
dose of study drug.
8. Clinically significant toxic effects of previous therapy have recovered to Grade 1
(per NCI CTCAE Version 5.0) or baseline, except for alopecia, Grade 2 peripheral
neuropathy, and/or autoimmune endocrinopathies with stable endocrine replacement
therapy.
9. In dose escalation Part 1, (not applicable for the Japan safety lead-in) once
peripheral evidence of dazostinag pharmacodynamic stimulation of the innate and/or
adaptive immune system is observed in the blood and/or an imaging response/partial
response (CR/PR) is observed in at least 1 participant, subsequent participants
must:
- Have at least 1 lesion amenable for biopsy.
- Agree to have 2 tumor biopsies: 1 during the screening period and 1 while on
dazostinag treatment.
10. Must have at least 1 RECIST version 1.1-evaluable (measurable) lesion. For the dose
escalation phase (Part 1) only, nonmeasurable only disease is acceptable.
11. Pharmacokinetic (PK)/pharmacodynamic blood must be drawn on a peripherally-inserted
catheter. Dazostinag is preferentially administered through a central line, but
peripheral infusion is acceptable. If a peripheral line is used for dazostinag
and/or pembrolizumab infusion, it must be separate than the one used for
PK/pharmacodynamic collection.
1. Corrected QT interval by Fredericia (QTcF) greater than (>) 450 milliseconds (men)
or > 475 milliseconds (women) on a 12-lead electrocardiogram (ECG) during the
screening period.
2. Grade greater than or equal to (≥) 2 hypotension (that is, hypotension for which
nonurgent intervention is required) at screening or during Cycle 0 Day 1 (C0D1) [for
Japan safety lead-in only] and Cycle 1 Day 1 (C1D1) predose assessment.
3. Oxygen saturation less than (<) 92 percent (%) on room air at screening or during
C0D1 (for Japan safety lead-in only) and C1D1 predose assessment.
4. Treated with other STING agonists/antagonist and toll-like receptors agonists within
the past 6 months.
5. Current history of pneumonitis, interstitial lung disease, severe chronic
obstructive pulmonary disease, idiopathic pulmonary fibrosis, other restrictive lung
diseases, acute pulmonary embolism, or Grade ≥ 2 pleural effusion or ascites not
controlled by tap or requiring indwelling catheters.
6. History of brain and leptomeningeal metastasis unless:
- Brain metastases are clinically and radiologically stable or improved (that is,
≥ 4 weeks) following surgery, whole-brain radiation, or stereotactic
radiosurgery, AND
- Off corticosteroids.
7. Ongoing Grade ≥ 2 infection or participants with Grade ≥ 2 fever of malignant
origin.
8. Chronic, active hepatitis (example: participants with known hepatitis B surface
antigen seropositive and/or detectable hepatitis C virus [HCV]- ribonucleic acid
[RNA]).
9. For participants in the dose escalation SA Part 1A only: refusal of standard
therapeutic options.
10. For participants receiving pembrolizumab only: contraindication and/or intolerance
to the administration of pembrolizumab.
11. For participants receiving chemotherapy in Part 2B: contraindication and/or
intolerance to the administration of both platinum agents (cisplatin and
carboplatin) and/or 5-FU.
12. Participant has had any other prior or concurrent malignancy within 2 years prior to
enrollment with the following exceptions: adequately treated localized basal cell or
squamous cell carcinoma, or curatively treated in situ carcinoma of the cervix or
breast. Other exceptions may be considered upon sponsor consultation.
13. Concurrent chemotherapy (except for Part 2B), immunotherapy (except for
pembrolizumab in Part 1B, Part 2, and Part 3), biologic, or hormonal therapy (except
for adjuvant endocrine therapy for a history of breast cancer). Concurrent use of
hormones for noncancer-related conditions is acceptable (except for corticosteroid
hormones) unless allowed per exclusion criterion 16.
14. Radiation therapy within 14 days (42 days for radiation to the lungs) and/or
systemic treatment with radionuclides within 42 days before C1D1 of study drug(s).
Participants with clinically relevant ongoing pulmonary complications from prior
radiation therapy are not eligible.
15. Use of systemic corticosteroids or other immunosuppressive therapy, concurrently or
within 7 days of C1D1 of study drug(s), with the following exceptions:
- Topical, intranasal, inhaled, ocular, intra-articular, and/or other
non-systemic corticosteroids.
- Premedications required for computed tomography (CT) or magnetic resonance
imaging (MRI) scans.
- Physiological doses of replacement steroid therapy (example: for adrenal
insufficiency).
- For participants enrolled in Part 2B, chemotherapy premedication with steroids
can be administered according to local standards of care practice.
16. Use of medications that are known clinical organic anion-transporting polypeptide B1
(OATP1B1) and/or OATP1B3 inhibitors, concurrently or within 14 days of C1D1 of study
drug(s).
17. Receipt of live attenuated vaccine (eg, tuberculosis Bacillus Calmette-Guerin
vaccine, oral polio vaccine, measles, rotavirus, yellow fever) within 28 days of
C1D1 of study drug(s).
18. Recipients of allogeneic or autologous stem cell transplantation or organ
transplantation.
For Part 2 SCCHN only:
19. Has progressive disease (PD) within 6 months of completion of curatively intended
systemic treatment for locoregionally advanced SCCHN.
20. Has a life expectancy of less than 3 months and/or has rapidly PD (eg, tumor
bleeding, uncontrolled tumor pain) in the opinion of the treating investigator.
21. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 or
anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agent.
22. Participants with known dihydropyrimidine dehydrogenase (DPD) deficiency or
thymidine phosphorylase gene (TYMP) mutations (Part 2B only).