Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Pembrolizumab

Fluorouracil

Cisplatin

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

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

Patients eligible for an investigator initiated trial are given the standard PIS by email, and are also emailed a summary PIS and access to an online set of 10 video educational modules. They are then administered a demographic data collection form, the Quality of Informed Consent Questionnaire Parts A and B, and a user feedback survey form. They then present for their standard of care consent visit.

Patients eligible for an investigator initiated trial are given the standard PIS by email and are then administered a demographic data collection form, the Quality of Informed Consent Questionnaire Parts A and B, and a user feedback survey form. They will then be emailed and are also emailed a summary PIS and access to an online set of 10 video educational modules. They will then perform the QuIC-A and QuIC-B again. They will then present for their standard of care consent visit.

Complex trial information presented in alternative and more accessible formats

Summary PIS and Online Video Modules

Juanita Lopez, MRCP PhD

Abhijit Pal, MBBS FRACP

Ann Gandolfi

The purpose of the trial will be to test whether providing both a short summary PIS and a link to a set of online video modules will improve patient understanding (those considering early phase clinical trials) as measured on the Quality of Informed Consent questionnaire (Part A), as compared to a control group who are provided only the normal PIS, and also to assess user acceptability and feasibility of these interventions.

i. General background

Early phase oncology clinical trials are becoming increasingly complex with a rapidly increasing array of investigational agents, combinations of these agents and a variety of trial designs which incorporate the importance of personalised approaches and the hope of fast tracked drug discovery. Informed consent for early phase oncology trials has always been a contentious area, and now it continues to be of relevance for the wider oncology community and the Phase 1 trial community. A 2018 study demonstrated significant gaps in understanding of patients regarding the nature and intent of early phase oncology trials. There has been a longstanding debate in the medical oncology community about the nature of Phase 1 trials and the ethics of allowing vulnerable patients to participate in clinical research where the primary purpose is to establish the safe dose. Opponents of the argument point to the need to understand both sides and that patients need to understand enough to consent, which is not necessarily full comprehension. The fact that this group of patients is hopeful, optimistic and desperate has been well characterized and no doubt plays a role in their ability to process information presented to them by the clinical research team.

ii. Empirical research showing patients misunderstand early phase clinical trials

Multiple studies have shown that advanced cancer patients (ACP) misunderstand the nature and purpose of Phase 1 oncology trials. Most recently, Hlubocky et al. demonstrated through audiotaping clinical encounters between 101 ACPs, and 29 oncologists that ACPs had a poor understanding. Only 26% were able to recall the primary purpose of the trial as safety and only 7% were able to recall that there was a risk of major adverse effects such as organ damage. The study also demonstrated deficiencies in clinician communication, with only 40% of encounters containing a direct statement on the research purpose being to establish safety, toxicity and dosage. In 2010, a similar study of 17 oncologists and 52 patients in the United Kingdom showed that several key areas of information including prognosis were omitted from the clinical encounter.Joffe and colleagues also conducted a survey of trial participants (including phase 1, 2 and 3 clinical trials) and investigators and showed significant deficits in understanding. Furthermore, in a survey of 95 patients on Phase 1 trials, Pentz and colleagues demonstrated that 68.4% of patients had a therapeutic misconception by failing to answer two core questions correctly ("Is the research study mostly intending to help research and gain knowledge or mostly intending to help you as a person?" and "Does the research study or your doctor decide the treatments?"). There was also a misunderstanding of the risk associated with participating in an early phase clinical trial and that they do not correctly grasp the key difference between individualized care and clinical research. There was a correlation between lower education and lower family incomes with therapeutic misconception. Overall there is extensive empirical evidence to suggest that a significant proportion of advanced cancer patients considering early phase oncology clinical trials harbour misconceptions about the nature and design of these trials.

iii. Participant Information Sheets are too long, too complex and fail to meet the information needs of patients

It has long been recognised that Participant Information Sheets (PIS) or Informed Consent Forms (ICF) are highly complex and lengthy across all the phases of oncology clinical trials. In 2007, Beardsley and colleagues showed that PIS were increasing in length and that an objective measure of informed consent (the QuIC-A), understanding decreased as PIS's increased in length. There have been no published studies on the PIS used in Phase 1 studies specifically. However, in the era of combination trials, Bayesian adaptive design, and seamless Phase 1/2 designs, the PIS for Phase 1 trials can be particularly complex. There is regulatory requirement for disclosure and there are certain regulatory requirements but these documents have ultimately become unwieldy, disliked by investigators and anecdotally, not read at all by participants. This further magnifies the issues on therapeutic misconception that were highlighted earlier. We note that the Hastings Center has published a 3 page Phase 1 consent form, but to the best of our knowledge this is not in widespread practice. Overall, in this era of increasingly sophisticated trial design, PIS are becoming lengthier and are becoming less useful as adjuncts to the informed consent process.

iv. Paucity of interventional research to improve understanding

We performed a review of the literature looking at interventions that have been tested to improve participant comprehension of Phase 1 trials which yielded two relevant studies. The first, a simulated teaching intervention to improve clinician confidence by Fallowfield et al. (2012) showed that an intensive 8 hour educational intervention on clinicians involved in early phase trials improved their self-confidence along with patient simulator ratings of understanding(7). Secondly, Kass et al. (2009) randomized 288 participants to receive either a 20 minute educational computer based presentation or a standard pamphlet on clinical trials and showed that they could improve patient understanding of trial purpose from 16% to 34%(8) and also showed that there was no significant differences in likelihood of enrollment. We note that there have been multiple efforts directed towards empowering cancer patients in later phase trials including audiovisual techniques such as multimedia presentations(9), question prompt lists(10), and decision aids (11). Promisingly, sponsors are already taking steps towards improving their information sheets and there are already attempts to incorporate audiovisual materials and electronic assessment of patient understanding.

v. Justification for CONSENT

CONSENT will be a randomised controlled trial examining the effect of both a short, jargon-free, plain language participant information sheet and a suite of online educational videos, on participants considering consenting to an investigator initiated trial within the Drug Development Unit. Early phase trials have dramatically changed over the last decade and there have been no interventional studies published in this area in this time and consequently this is a significant area of unmet need for both patients and investigators. This trial will use a validated measure of informed consent (Quality of Informed Consent - Part A) and powered to test a statistical hypothesis, and will also examine the acceptability of the two interventions for patients. While the trial will employ a randomised design, it will ensure all participants are provided access to the enhanced consent materials prior to their actual consent visit to ensure fairness. This trial will be conducted in compliance with the protocol, standard operating procedures, policies, local R\&D management guidance, Good Clinical Practice including the UK Policy Framework for Health and Social Care.

Research Governance Framework 2005 (2nd edition)

2. Rationale

Given the ethical imperative to ensure patients understand the nature and conduct of clinical trials, the clearly documented lack of understanding in the literature, we propose this trial to examine whether a pragmatic and deliverable program of "enhanced" informed consent can impact upon patient objective and subjective understanding. The first part of this enhanced consent will be a summary PIS (example attached in appendix) which contains the absolutely necessary information for patients - we have already conducted a qualitative study of patient focus groups and have asked patients directly their priorities. The top three priorities identified patients were

1. Will this trial work for me?
2. What are the side effects?
3. How often do I have to come? This will consist of an easy to understand flowchart.

The second part of this enhanced consent will be an online link to 10 video modules (transcripts attached in appendix) covering key areas of the consent. During the development process of these educational tools, we performed a qualitative analysis of transcripts of interviews of consultants, study managers, clinical fellows, clinical research nurses and patients of the DDU and identified the key areas that the various stakeholders wished to communicate to patients. We asked about the key areas that need to be communicated, common areas of misunderstanding and preferred ways forward of improving patient understanding.

Improving Informed Consent for Early Phase Anti-Cancer Trials

A Randomised Controlled Trial of Enhanced Informed Consent Compared to Standard Informed Consent To Improve Patient Understanding of Early Phase Oncology Clinical Trials

• To determine the QuIC Part A scores following administration of a standard PIS alone, and compare it to the QuIC Part A score following administration of a standard PIS along with a summary PIS and a suite of online educational videos. Minimum score on QuIC-A is 0, highest is 100, and higher scores indicate a higher degree of objective understanding of clinical trial principles.

• To determine the QuIC Part B scores following administration of a normal PIS alone, and compare it to the QuIC Part B score following administration of a normal PIS along with a summary PIS and a suite of online educational videos. Minimum score on QuIC-B is 0, highest is 100, and higher scores indicate a higher degree of subjective understanding of clinical trial principles.

• To determine the changes in QuIC Part A and Part B scores before and after administration of enhanced consent materials

• To confirm the acceptability and utility of the summary PIS and educational videos with a user feedback survey

QuIC Part A and Part B scores before and after administration of enhanced consent materials in patients recruited to the GBM cohort in the ICE-CAP study

Royal Marsden NHS Foundation Trust

Participants receive MK-7162 25 mg via oral tablets once daily (QD) throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 25 mg orally QD PLUS pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (every 3 weeks \[Q3W\]).

Participants receive MK-7162 50 mg via oral tablets QD throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-71625 50 mg orally QD PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle Q3W

Participants receive MK-7162 100 mg via oral tablets QD throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 100 mg orally QD PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle Q3W

Participants receive MK-7162 200 mg via oral tablets QD throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 200 mg orally QD PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle Q3W

MK-7162

Medical Director

The purposes of this study are to determine the safety and tolerability of MK-7162 when administered in combination with pembrolizumab (MK-3475) and to establish a preliminary recommended Phase 2 dose (RP2D) of MK-7162 when administered in combination with pembrolizumab.

Study of MK-7162 in Combination With Pembrolizumab (MK-3475) in Adult Participants With Advanced Solid Tumors (MK-7162-002)

Phase 1b Open-label Study of MK-7162 in Combination With Pembrolizumab (MK-3475) +/- Other Therapies in Participants With Advanced Solid Tumors

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

The following events, if considered drug related by the investigator, are considered a DLT: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia of any duration; Grade 3 thrombocytopenia associated with bleeding; Nonhematologic Adverse Events (AE) ≥Grade 3 with exceptions; Grade 3 or Grade 4 non-hematologic laboratory values if requires medical intervention, leads to hospitalization, persists for \>1 week, or results in a Drug-induced Liver Injury with exceptions; Grade 3 of 4 febrile neutropenia; Treatment-related toxicities that lead to discontinuation of study treatment during Cycles 1 or 2; Prolonged delay (\>2 weeks) in initiating Cycles 2 or 3 due to treatment-related toxicity; Missing \>25% of MK-7162 doses as a result of treatment-related AE during Cycles 1 or 2; Grade 5 toxicity.

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Blood samples were collected at designated time points for determining the AUC₀-₈ of MK-7162 in plasma when administered alone and in combination with pembrolizumab.

Blood samples were obtained at designated time points to determine the Cmin of MK-7162 in plasma.

Blood samples were collected at designated time points to determine the Cmax of MK-7162 in plasma when administered alone and in combination with pembrolizumab.

MK-7162 is a selective inhibitor of Indoleamine-2,3-dioxygenase-1 (IDO1) activity which, in turn, reduces the conversion of TRP to KYN. Venous blood samples were collected after an overnight fast for measurement of plasma levels of KYN as a pharmacodynamic biomarker of IDO1 inhibition.

MK-7162 is a selective inhibitor of Indoleamine-2,3-dioxygenase-1 (IDO1) activity which, in turn, reduces the conversion of TRP to KYN. Venous blood samples were collected at designated time points after an overnight fast for measurement of plasma levels of TRP as a pharmacodynamic biomarker of IDO1 inhibition.

ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by the Investigator. The percentage of participants who experience a CR or PR based on RECIST 1.1 will be presented.

Participants with PD by RECIST 1.1 as determined by investigator underwent confirmatory imaging to classify the disease as confirmed progressive disease (iCPD), unconfirmed progressive disease \[iUPD\]), stable disease (iSD), partial response (iPR) or complete response (iCR). iCPD definition: Worsening of target lesions (increase in the sum of diameters of ≥5 mm); Any significant growth in non-target lesions, Appearance of new lesions, increase in new lesion sum of diameters by ≥5 mm; Visible growth of new non-target lesions; or appearance of new factor that would have triggered PD by RECIST 1.1. Responses are classified as iSD or iPR (depending on the sum of diameters of the target lesions), or iCR if all lesions resolve. iUPD overall response is defined as none of the progression-confirming factors identified in iCPD occurs AND The target lesion sum of diameters (initial target lesions) remains above the initial PD threshold (by RECIST 1.1)

Merck Sharp & Dohme LLC

The safety analysis population includes all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study treatment. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as AEs.

Participants receive MK-7162 25 mg via oral tablets QD throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 25 mg orally QD PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle Q3W

MK-7162 25mg + Pembro

Participants receive MK-7162 50 mg via oral tablets QD throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 50 mg orally QD PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle Q3W

MK-7162 50mg + Pembro

MK-7162 100mg + Pembro

MK-7162 200mg + Pembro

MK-7162 25 mg + Pembro

MK-7162 50 mg + Pembro

MK-7162 100 mg + Pembro

MK-7162 200 mg + Pembro

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Senior Vice President, Global Clinical Development

All participants who received at least one dose of study treatment and were observed for safety for 21 days after the first dose of assigned treatment or experienced a DLT prior to 21 days after the first dose of treatment.

Number of Participants Experiencing Dose-limiting Toxicities (DLTs) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 by the Investigator

All participants who received at least one dose of study treatment

Number of Participants Who Experienced an Adverse Event (AE)

Number of Participants Who Discontinued Study Drug Due to an AE

Day 1, Cycle 1: MK-7162 alone

Day 15, Cycle 1: MK-7162 alone

Day 1, Cycle 3: MK-7162 + Pembrolizumab

All participants who were compliant with the study procedures and have available data from at least one treatment.

Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab

All participants who were compliant with the study procedures and have available plasma data.

Minimum Plasma Concentration (Cmin) of MK-7162

Day 1 Cycle 1: MK-7162 alone

Day15 Cycle 1: MK-7162 Alone

Day 1 Cycle 3: MK-7162+ Pembrolizumab

Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab

Cycle 1 Day 1, Predose

Cycle 1 Day 1, 1 Hour (hr) Postdose

Cycle 1 Day 1, 2 Hr Postdose

Cycle 1 Day 1, 4 Hr Postdose

Cycle 1 Day1, 8 Hr Postdose

Cycle 1 Day 15, Predose

Cycle 1 Day 15, 1 Hr Postdose

Cycle 1 Day 15, 2 Hr Postdose

Cycle 1 Day 15, 4 Hr Postdose

Cycle 1 Day 15, 8 Hr Postdose

Cycle 2 Day 1, Predose

Cycle 3 Day 1, Predose

Cycle 3 Day 1, 1 Hr Postdose

Cycle 3 Day 1, 2 Hr Postdose

Cycle 3 Day 1, 4 Hr Postdose

Cycle 3 Day 1, 8 Hr Postdose

Cycle 3 Day 15, PreDose

All participants who were compliant with the study procedures and have available data from at least one treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Dazostinag as Single Agent and Dazostinag in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors	NCT04420884	Solid Neoplasms	Dazostinag Pembrolizumab Platinum 5-fluorouracil	18 Years -	Takeda
Improving Informed Consent for Early Phase Anti-Cancer Trials	NCT04407676	Solid Neoplasms	Summary PIS and...	18 Years -	Royal Marsden NHS Foundation Trust
Study of MK-7162 in Combination With Pembrolizumab (MK-3475) in Adult Participants With Advanced Solid Tumors (MK-7162-002)	NCT03364049	Solid Neoplasms	MK-7162 Pembrolizumab	18 Years -	Merck Sharp & Dohme LLC
Celsius TCS Hyperthermia System PMCF Trial	NCT02896049	Solid Neoplasms	Hyperthermia	18 Years - 99 Years	Celsius42 GmbH
Celsius TCS Hyperthermia System PMCF Trial	NCT02896049	Solid Neoplasms	Hyperthermia	18 Years - 99 Years	Celsius42 GmbH
Safety Study of a Liposomal Docetaxel Formulation in Patients With Solid Tumors Who Have Failed Previous Therapies	NCT01041235	Solid Tumor Breast Cancer Ovarian Cancer Pancreatic Canc... Non-Small Cell ...	ATI-1123 (activ...	18 Years -	Azaya Therapeutics, Inc.
Endoscopic Ultrasonography (EUS) Guided Fine Needle Aspiration Using Free Stylet 22g and 25 g Needles	NCT01543282	Solid Neoplasms	Endosonography ...	18 Years -	Centre hospitalier de l'Université de Montréal (CHUM)
Study of MK-7162 in Combination With Pembrolizumab (MK-3475) in Adult Participants With Advanced Solid Tumors (MK-7162-002)	NCT03364049	Solid Neoplasms	MK-7162 Pembrolizumab	18 Years -	Merck Sharp & Dohme LLC
A Study of E7386 in Participants With Advanced Solid Tumor Including Colorectal Cancer (CRC)	NCT03833700	Solid Neoplasms Colorectal Neop... Gastrointestina...	E7386	18 Years -	Eisai Inc.

Spots Global Cancer Trial Database for solid neoplasms