A study in which the investigational drug TAK-676 is administered alone or in combination with another drug called Pembrolizumab with or without standard chemotherapy to patients with advanced head and neck carcinoma or advanced colorectal cancer

Austria, Belgium, Canada, China, France, Israel, Japan, Poland, Puerto Rico, Switzerland, United Kingdom, United States (ICTRP)

ID di studio ICTRP
NCT04420884 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
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 (BASEC)

Titolo accademico
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 (ICTRP)

Titolo pubblico
A Study of Dazostinag as Single Agent and Dazostinag in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors (ICTRP)

Malattie studiate
Solid Neoplasms (ICTRP)

Intervento studiato
Drug: DazostinagDrug: PembrolizumabDrug: PlatinumDrug: 5-fluorouracil (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Criteri di inclusione/esclusione
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) lesi (ICTRP)

non disponibile

Endpoint primari e secondari
Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Based on TEAEs Severity;Number of Participants with Dose-Limiting Toxicities (DLTs);Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAEs);Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations (ICTRP)

Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Overall Response Rate (ORR);Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Disease Control Rate (DCR);Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Duration of Response (DOR);Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Time to Response (TTR);Expansion Phase Only: Progression-Free Survival (PFS);Expansion Phase Only: Overall Survival (OS);Expansion Phase Only: OS Rate at 12 Months;Expansion Phase Only: OS Rate at 6 Months (ICTRP)

Data di registrazione
non disponibile

Inclusione del primo partecipante
non disponibile

Sponsor secondari
non disponibile

Contatti aggiuntivi
Study Director;Takeda Contact, medinfoUS@takeda.com, +1-877-825-3327, Takeda, (ICTRP)

ID secondari
U1111-1241-4427, 2023-505627-30-00, jRCT2031230532, TAK-676-1002 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT04420884 (ICTRP)