Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Rare Diseases

Small Cell Lung Carcinoma

Melanoma

Carcinoma, Non-Small-Cell Lung

Head and Neck Neoplasms

Neoplasm Metastasis

Lung Neoplasms

Mesothelioma

Mesothelioma, Malignant

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neoplasms by Histologic Type

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms, Mesothelial

Small Cell Lung Cancer

Malignant Mesothelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Escalating doses of CTX-471 depending on cohort at enrollment

Two dose groups of CTX-471 (0.3 mg/kg and 0.6 mg/kg)

Escalating doses of CTX-471 in combination with pembrolizumab (KEYTRUDA® ) depending on cohort at enrollment

Two cohorts of CTX-471 (0.3 mg/kg and 0.6 mg/kg) in combination with pembrolizumab (KEYTRUDA® ) (400 mg) in three tumor type subgroups. Cohort 1 - Group 1A - NSCLC , Group 1B -SCLC and Group 1C - Melanoma. Cohort 2 Group 2A - NSCLC, Group 2B - SCLC and Group 2C -Melanoma.

CTX-471

Pembrolizumab (KEYTRUDA®)

Natalie Warholic

Seth Rosen, MD

Tanner Johanns, MD

Martin Gutierrez, MD

Jennifer Choe, MD, PhD

W. Jeffrey Edenfield, MD

Minal Barve, MD

Thomas Scheutz, MD, PhD

This is a Phase 1, open-label, first-in-human study of CTX-471 administered as a monotherapy or in combination with pembrolizumab in patients with metastatic or locally advanced malignancies that have progressed while receiving an approved PD-1 or PD-L1 inhibitor. The study will be conducted in 2 treatment arms (Monotherapy Arm 1 and Combination Arm 2). Each arm will have two parts: Part 1 Dose Escalation and Part 2 Dose Expansion.

Study of CTX-471 as a Monotherapy or in Combination With Pembrolizumab in Patients Post PD-1/PD-L1 Inhibitors in Metastatic or Locally Advanced Malignancies

A Phase 1, Open-Label, Multiple-Ascending Dose Study of the Safety and Tolerability of CTX-471 Administered Either as a Monotherapy or in Combination With Pembrolizumab in Patients With Inadequate Responses to PD-1/PD-L1 Checkpoint Inhibitors in Metastatic or Locally Advanced Malignancies

ORR will be calculated as the number of participants with a confirmed complete response (CR) or a partial response (PR) divided by the number of participants dosed

Iqvia Pty Ltd

Merck, Sharp & Dohme, LLC, Rahway, NJ USA

Compass Therapeutics

Digestive System Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Death

Breast Neoplasms

Triple Negative Breast Neoplasms

Pancreatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Breast Diseases

Skin Diseases

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Gastrointestinal Agents

Pancrelipase

Pancreatin

NT-I7 will be administered on Day 1 of alternate 21 day cycles (Cycle 1, 3, 5 etc.). Dosage will increase until the maximum tolerated dose (MTD) and/or the recommended phase 2 (RP2D) dose is reached.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) treated relapsed or refractory triple negative breast cancer (TNBC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) treated relapsed or refractory non-small cell lung cancer (NSCLC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) treated relapsed or refractory small cell lung cancer (SCLC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) naïve relapsed or refractory microsatellite stable colorectal cancer (MSS-CRC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) naïve relapsed or refractory pancreatic cancer (PC). Participants will receive the recommended phase 2 dose (RP2D) identified during Phase 1b.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) naïve relapsed or refractory microsatellite stable colorectal cancer (MSS-CRC). Participants will receive 1200 µg/kg of NT-I7 and and a fixed dose of 200 mg of pemprolizumab.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) naïve relapsed or refractory pancreatic cancer (PC).Participants will receive 1200 µg/kg of NT-I7 and a fixed dose of 200 mg of pemprolizumab.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Participants with checkpoint inhibitor (CPI) naïve relapsed or refractory ovarian cancer (OC). Participants will receive a starting dose of 960 µg/kg of NT-I7 and a fixed dose of 200 mg of pemprolizumab.

Pembrolizumab will be administered on Day 1 of every 21 day cycle.

Administered by intramuscular (IM) injection

NT-I7

Administered by intravenous (IV) injection

pembrolizumab (KEYTRUDA®)

The main purposes of Phase 1b of this study are to determine the following in participants with advanced solid tumors:

* Safety and tolerability of NT-I7 in combination with pembrolizumab
* Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D)

The main purpose of Phase 2a of this study is to assess the preliminary anti-tumor activity of NT-I7 in combination with pembrolizumab in participants with checkpoint inhibitor (CPI) treated and naïve relapsed and refractory (R/R) tumors.

The main purpose of the Biomarker Cohort is to assess a potential correlation between tumor infiltrating lymphocytes (TILs) and clinical benefits in participants with CPI-naïve R/R ovarian cancer (OC).

This is a multicenter, open-label Phase 1b/2a study of NT-I7 in combination with pembrolizumab. The study consists of a dose escalation phase (Phase 1b) followed by a dose expansion phase (Phase 2a) and a Biomarker Cohort.

The Phase 1b is designed to assess the safety and tolerability, including determination of the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of NT-I7.

The main purpose of Phase 2a of this study is to assess the preliminary antitumor activity of NT-I7 in combination with pembrolizumab in participants with relapsed/refractory

* checkpoint inhibitor (CPI)-treated Triple Negative Breast Cancer (TNBC), Non-small Cell Lung Cancer (NSCLC), and Small Cell Lung Cancer (SCLC)
* checkpoint inhibitor (CPI)-naïve Microsatellite Stable Colorectal Cancer (MSS-CRC), and Pancreatic Cancer (PC) The Biomarker Cohort is designed to assess the correlation between tumor infiltrating lymphocytes (TILs) and clinical benefits of NT-I7 in combination with pembrolizumab in participants with CPI naïve R/R Ovarian Cancer (OC).

NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

An Open-label Phase 1b/2a Study of NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Advanced Solid Tumors

* Incidence, nature and severity of Adverse Events (AEs) graded according to NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
* Incidence and nature of Dose-Limiting Toxicities (DLTs)

Statistical correlation of dose levels with safety and efficacy parameters.

TILs in tumor biopsy samples will be identified using a multi-spectral Immunofluorescence (IF) assay.

Merck Sharp & Dohme LLC

NeoImmuneTech

Nervous System Diseases

Heart and Blood Diseases

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Immune System Diseases

Ataxia

Cerebellar Ataxia

Telangiectasis

Ataxia Telangiectasia

Hormones

Immunomodulating Agents

Mitogens

Participants with advanced hormone-receptor-positive, Human epidermal growth factor receptor 2 negative breast cancer (HER2-negative BC), known to be positive for Ataxia-telangiectasia mutated (ATM) loss and/or ATM deleterious alterations who have not received prior treatment with immunotherapy. Participants with known microsatellite instability-high (MSI-H) cannot be included

Participants with advanced hormone-receptor-positive, HER2-negative BC, known to be DDR deficiency biomarker-positive (except ATM loss/mutation) who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.

Participants with advanced Colorectal cancer (CRC) known to be positive for ATM loss and/or ATM deleterious alterations who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.

Participants with advanced CRC, known to be DDR deficiency biomarker -positive (except ATM loss/mutation) who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.

Participants with advanced Gastric/gastroesophageal junction cancer (GC/GEJ) known to be DDR deficiency biomarker-positive (incl. ATM mutation) and/or positive for ATM loss. Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies.

Participants with advanced GC/GEJ cancer and without DDR deficiency alterations as described above. Variants of unknown significance (VUS) of the DDR gene alterations are eligible. Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies.

Participants with advanced Non-small cell lung cancer (NSCLC) known to be DDR deficiency biomarker-positive (incl. ATM mutation) and/or positive for ATM loss. Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies.

Participants with advanced NSCLC and without DDR deficiency alterations as described above. VUS of the DDR gene alterations are eligible. Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies.

Participants with advanced pancreatic cancer, known to be DDR deficiency biomarker-positive (incl. ATM mutation) and/or positive for ATM loss who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.

Participants with advanced pancreatic cancer and without DDR deficiency alterations as described above, who have not received prior treatment with immunotherapy. VUS of the DDR gene alterations are eligible. Participants with known MSI-H cannot be included.

Participants with advanced Metastatic castration-resistant prostate cancer (mCRPC), known to be DDR deficiency biomarker positive (incl. ATM mutation) and/or positive for ATM loss who have not received prior treatment with immunotherapy. Participants with known MSI-H cannot be included.

Participants with advanced mCRPC and without DDR deficiency alterations as described above, who have not received prior treatment with immunotherapy. VUS of the DDR gene alterations are eligible. Participants with known MSI-H cannot be included.

Study drugs will be administered as scheduled

Elimusertib (BAY1895344)

Pembrolizumab (Keytruda®)

The purpose of the study is to test how well patients with advanced solid tumors respond to treatment with elimusertib (BAY1895344) in combination with pembrolizumab. In addition researchers want to find for patients the optimal dose of elimusertib in combination with pembrolizumab, how the drug is tolerated and the way the body absorbs, distributes and discharges the drug. The study medication, elimusertib, works by blocking a substance (ATR Kinase) which is produced by the body and is important for the growth of tumor cells. Pembrolizumab is an immunologic checkpoint blocker that promotes an immune response against the tumor.

Study to Test How Well Patients With Advanced Solid Tumors Respond to Treatment With the Elimusertib in Combination With Pembrolizumab, to Find the Optimal Dose for Patients, How the Drug is Tolerated and the Way the Body Absorbs, Distributes and Discharges the Drug

A Multicenter, Non-randomized, Open-label Phase 1b Study to Determine the Maximum Tolerated and Recommended Phase 2 Dose of the ATR Inhibitor Elimusertib in Combination With Pembrolizumab and to Characterize Its Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity in Participants With Advanced Solid Tumors

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

The RP2D will be determined in dose expansion part based on multiple parameters (i.e., safety, tolerability, PK, pharmacodynamics, efficacy) and will be a dose equal to or lower than the MTD (Maximum Tolerated Dose).

If the main parameters AUC(0-12) cannot be calculated reliably, it might become necessary to appoint the additional parameters AUC(0-tlast) as secondary variables.

If the main parameters AUC(0-12)md cannot be calculated reliably, it might become necessary to appoint the additional parameters AUC(0-tlast)md as secondary variables.

Per RECIST 1.1 and for participants with mCRPC consistent with recommendations of the Prostate Cancer Working Group (PCWG3)

Bayer

Blood and Lymph Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Carcinoma, Squamous Cell

Lymphoma

Uterine Cervical Neoplasms

Carcinoma, Transitional Cell

Nasopharyngeal Carcinoma

Lymphosarcoma

Transitional Cell Carcinoma

Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy.

Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 in combination with pembrolizumab.

Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy; additional subjects in each cohort may be enrolled in Stage 2.

Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 in combination with pembrolizumab; additional subjects in each cohort may be enrolled in Stage 2.

FLX475

William Ho, MD, PhD

This clinical trial is a Phase 1/2, open-label, sequential-group, dose-escalation and cohort expansion study to determine the safety and preliminary anti-tumor activity of FLX475 as monotherapy and in combination with pembrolizumab.

The study will be conducted in 2 parts, a dose-escalation phase (Part 1) and a cohort expansion phase (Part 2). In Part 1 of the study, subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy or in combination with pembrolizumab. In Part 2 of the study, subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy or in combination with pembrolizumab.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of CTX-471 as a Monotherapy or in Combination With Pembrolizumab in Patients Post PD-1/PD-L1 Inhibitors in Metastatic or Locally Advanced Malignancies	NCT03881488	Locally Advance... Metastatic Canc... Non-small Cell ... Small Cell Lung... Mesothelioma Melanoma Head and Neck C...	CTX-471 Pembrolizumab (...	18 Years -	Compass Therapeutics
NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Participants With Advanced Solid Tumors	NCT04332653	Any Advanced So... Triple Negative... Non Small Cell ... Small Cell Lung... Microsatellite ... Pancreatic Canc... Ovarian Cancer	NT-I7 pembrolizumab (...	18 Years -	NeoImmuneTech
Study to Test How Well Patients With Advanced Solid Tumors Respond to Treatment With the Elimusertib in Combination With Pembrolizumab, to Find the Optimal Dose for Patients, How the Drug is Tolerated and the Way the Body Absorbs, Distributes and Discharges the Drug	NCT04095273	Advanced Solid ...	Elimusertib (BA... Pembrolizumab (...	18 Years -	Bayer
Dose Escalation and Expansion Study of FLX475 Monotherapy and in Combination With Pembrolizumab	NCT03674567	Advanced Cancer	FLX475 pembrolizumab (...	18 Years -	RAPT Therapeutics, Inc.

Spots Global Cancer Trial Database for pembrolizumab (keytruda®)