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Safety Lead-in: Dazostinag 0.1 mg, infusion, intravenously (IV), once weekly, on Days 1, 8 and 15 in 21-day treatment cycles.

Dazostinag single agent (SA) Dose Escalation (Part 1A): Dazostinag SA, infusion, IV, once weekly on Days 1, 8 and 15 in each 21-day treatment cycles with escalating doses (0.2 mg and above). The dosing will be initiated in the Dazostinag SA Dose Escalation Phase based on the available safety and tolerability data from the Safety Lead-in.

Dazostinag escalating doses (0.2 mg and above) in combination with pembrolizumab 200 mg, infusion, IV, once weekly on Days 1, 8 and 15 in each 21-day treatment cycle. Pembrolizumab 200 mg will be administered 1 hour prior to Dazostinag once every 3 weeks (Q3W). The dosing will be initiated when at least two dose levels (DLs) of Part 1A have been evaluated.

Dazostinag 5.0 mg, infusion, IV, once on Day 1 in Cycle 0 (cycle length=7 days) in Japanese participants with advanced or metastatic solid tumors. Following the 7-day Cycle 0, participants who do not develop any DLT in Cycle 0 will be administered Dazostinag on Days 1, 8, and 15 of a 21-day cycle in combination with pembrolizumab administered Q3W, IV, in Cycle 1. If no DLTs are observed, study treatment will start with Dazostinag in combination with pembrolizumab administered on Day 1 of each 21-day treatment cycle.

Additional dose levels of Dazostinag (such as 3.5 mg or 7.0 mg and higher) in combination with pembrolizumab (200 mg, Q3W) may be explored in the Safety Lead in.

Dazostinag 5.0 mg, infusion, IV, will be administered in participants with squamous cell carcinoma of head and neck (SCCHN) at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W. Dose optimization may be performed in this phase.

Dazostinag 5.0 mg, infusion, IV, will be administered in participants with SCCHN at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle. Pembrolizumab infusion, IV will be administered at 200 mg Q3W. Platinum-based chemotherapy comprising the combination of carboplatin (target area under the curve of 5 mg/mL/minute\[AUC 5\]) or cisplatin (100 milligrams per square meter \[mg/m\^2\] Day 1 of each treatment cycle), and 5-fluorouracil (\[5-FU\]; 1000 mg/m\^2 per day for 4 consecutive days) every 3 weeks for up to 6 cycles.

Dazostinag 5.0 mg, infusion, IV, will be administered in participants with microsatellite instability-high /mismatch repair deficient (MSI-H/dMMR) colorectal cancer (CRC) at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W.

Dazostinag 5.0 mg, infusion, IV, will be administered in participants with microsatellite stable/mismatch repair proficient (MSS/pMMR) CRC at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle. along with pembrolizumab 200 mg infusion, IV, Q3W.

Dose optimization may be performed in this phase.

Dazostinag

Carboplatin or Cisplatin intravenous infusion

Platinum

5-fluorouracil

Takeda Contact

Site Contact

Sandip Patel

Heinz-Josef Lenz

Rupali Nabar

Zev Wainberg

Gerald Falchook

Patricia LoRusso

Jesus Fabregas Mercado

Tirrell Johnson

Jochen Lorch

Ranee Mehra

Xin Gao

Jacob Sands

Ammar Sukari

Douglas Adkins

Davendra Sohal

Rachel Sanborn

Anthony Olszanski

Jason Luke

Meredith Pelster

Douglas Orr

Mohamad Salkeni

Josef Thaler

Richard Greil

Birgit Grunberger

Hans Prenen

Sabine Tejpar

Michael Sawyer

Brandon Meyers

Philippe Bedard

Petr Kavan

Nathaniel Bouganim

Lin Shen

Yan-Hong Deng

Dongmei Ji

Ye Guo

Meng Qiu

Lei Liu

Meiyu Fang

Jaafar Bennouna-Louridi

Celine Gavoille

Christophe Borg

Amaury Daste

Melanie Dos Santos

Francois Ghiringhelli

Gautier Lefebvre

Jerome Fayette

Sebastien Salas

Thierry Andre

Ludovic changed to Mallet, Amelie Doucet

Caroline Even

Amichay Meirovitz

Aron Popovtzer

Ravit Geva

Tamar Beller

Yamamoto Noboru

Bogdan Zurawski

Lucjan Wyrwicz

Jose Lozada-Costas

Mirelis Acosta Riveli

Maria Garcia-Pallas

Dagmar Hess-Mildenberger

Martin D. Berger

Thibaud Koessler

Petr Szturz

David Cunningham

Victoria Coyle

Fiona Collinson

Martin Forster

Eileen Parkes

Study Director

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).

The drug being tested in this study is called dazostinag. Dazostinag is being tested to treat people who have advanced or metastatic solid tumors.

The study will enroll approximately 368 participants. Part 1 consists of an initial Safety Lead-in to Dose Escalation Phase; Part 2 and Part 3 compose the Expansion Phase in 2 specific indications namely, previously untreated metastatic or recurrent, unresectable SCCHN (Part 2) and third-line or later recurrent locally advanced or metastatic MSI-H/dMMR and third-line recurrent locally advanced or metastatic MSS/pMMR CRC (Part 3). Participants will be assigned to the following treatment groups in the respective Phases of the study:

* Part 1 (Dose Escalation Phase): Safety Lead-in + Dazostinag single agent (SA) \[Part 1A\] Dazostinag 0.1 milligram (mg) in the Safety Lead-in followed by Dazostinag as escalating doses (0.2 mg and above) in Part 1A
* Part 1B (Combination Dose Escalation Phase): Dazostinag as escalating doses (0.2 mg and above) + Pembrolizumab
* Japan Safety Lead-in: Dazostinag SA 5.0 mg in the Safety Lead-in+ Pembrolizumab. Additional dose levels of Dazostinag (such as 3.5 mg or 7.0 mg and higher) in combination with pembrolizumab may be explored during the Japan safety lead-in considering recommended dose for expansion (RDE1) as 5.0 mg and dose optimization.

Once a safe dose is recommended from Part 1, participants of select advanced or metastatic solid tumors will receive dazostinag in below defined cohorts in the expansion phase:

* Part 2A (SCCHN Combined Positive Score \[CPS\] ≥ 1 Dose Expansion Phase): Dazostinag + Pembrolizumab\*
* Part 2B (SCCHN Dose Expansion Phase): Dazostinag + Pembrolizumab + Chemotherapy
* Part 3A (Expansion Phase in CRC): Dazostinag + Pembrolizumab in MSI-H/dMMR CRC
* Part 3B (Expansion Phase in CRC): Dazostinag + Pembrolizumab in MSS/pMMR CRC\* \*Dose optimization will be performed in either Part 2A SCCHN or Part 3B CRC.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 62.9 months. Participants will make multiple visits to the clinic, including 30 days after last dose of study drug for a follow-up assessment. Participants in Parts 2 and 3 will be followed for survival for up to 12 months after the last dose of study drug.

A Study of Dazostinag as Single Agent and Dazostinag in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors

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

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

A severity grade is defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Grade 1 scales as Mild (asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 scales as Moderate (minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living \[ADL\]); Grade 3 scales as Severe (severe or medically significant but not immediately life threatening hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 scales as Life-threatening consequences, urgent intervention indicated, and Grade 5 scales as Death related to Adverse Event (AE).

A DLT will be defined as any of the TEAEs, but not limited to, those that occur during Cycle 1 and are considered by the investigator to be at least possibly related to dazostinag as a single agent (SA) or in combination with pembrolizumab. TEAEs meeting DLT definitions occurring in Cycle 2 or later will be considered in the determination of the RDE of dazostinag, both in the dazostinag SA and the combination with pembrolizumab arms. Toxicity will be evaluated according to NCI CTCAE version 5.0.

ORR is defined as the percentage of participants who achieve confirmed complete response (cCR) + confirmed partial response (cPR) during the study in response-evaluable population. ORR will be assessed based on Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1.

DCR is defined as the percentage of participants who achieve cCR + cPR + stable disease (SD) greater than (\>) 6 weeks during the study in response-evaluable population. The DCR will be assessed based on RECIST version 1.1.

DOR is the time from the date of first documentation of a cPR or better to the date of first documentation of progressive disease for responders (cPR or better). Responders without documentation of progressive disease will be censored at the date of last response assessment that is SD or better. DOR will be assessed based on RECIST version 1.1.

TTR is defined as the time from the date of first dose administration to the date of first documented cPR or better by the investigator. TTR will be assessed based on RECIST version 1.1.

PFS is defined as the time from the date of first dose administration to the date of first documented disease progression or death due to any cause, whichever occurs first.

OS is defined as the time from the date of first dose administration to the date of death.

12-month OS rate is defined as the percentage of participants who are still alive at 12 months from their first dose administration.

6-month OS rate is defined as the percentage of participants who are still alive at 6 months from their first dose administration.

Takeda

Spots Global Cancer Trial Database for dazostinag

Every month we try and update this database with for dazostinag cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for dazostinag

Every month we try and update this database with for dazostinag cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for dazostinag cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.