Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Stomach Neoplasms

Urinary Bladder Neoplasms

Melanoma

Carcinoma, Renal Cell

Head and Neck Neoplasms

Carcinoma, Transitional Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Stomach Cancer

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Transitional Cell Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Pembrolizumab

Immunoglobulins

Immunoglobulin G

Immunologic Factors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

INBRX-106 will be escalated in subjects with locally advanced or metastatic solid tumors.

INBRX-106 will be escalated, in combination with pembrolizumab, in subjects with locally advanced or metastatic solid tumors.

Subjects with melanoma (any type), head and neck squamous cell carcinoma (non-nasopharyngeal), nasopharyngeal carcinoma, MSI-high, TMB-high or MMR-deficient tumors, will be treated with INBRX-106 in combination with 200mg pembrolizumab IV every 3 weeks.

Subjects with non-small cell lung cancer will be treated with 200 mg pembrolizumab IV every 3 weeks

Subjects with non-small cell lung cancer will be treated with alternating every 6 weeks dosing of INBRX-106 0.3 mg/kg Q6W and 400 mg pembrolizumab IV

Subjects with non-small cell lung cancer will be given a 0.3 mg/kg priming dose of INBRX-106 in cycle 1, followed by 0.1 mg/kg INBRX-106 and 200 mg pembrolizumab IV every 3 weeks in subsequent cycles

Subjects with non-small cell carcinoma relapsed or refractory to prior checkpoint inhibitor (CPI) therapy will be treated with INBRX-106

Subjects with melanoma (any type), head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma or MSI/TMB-high tumors that are relapsed or refractory to prior checkpoint inhibitor (CPI) therapy will be treated with INBRX-106

Subjects with ocular (uveal) melanoma who are relapsed or refractory to checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 and 200 mg pembrolizumab IV every 3 weeks

Subjects with solid tumors that have confirmed MSI-high, TMB-high or MMR-deficient states who are relapsed or refractory to checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 and 200 mg pembrolizumab IV every 3 weeks

The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).

INBRX-106 - Hexavalent OX40 agonist antibody

Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.

Pembrolizumab 200 mg

Pembrolizumab 400 mg by IV infusion given on Day 1 of alternating 21-day cycles (every 6 weeks)

Pembrolizumab 400 mg

Amanda Sweeney, Trial Manager

Bonne Adams

New Patient Services

Erminia Massarelli, MD

Myo Zaw

David Berz, MD

Timothy Byun, MD

Suzanne Scott

Conor Steuer, MD

Kimberly Homere, MPH

Daniel Olson, MD

Jordan Harrelson

Muhammad Furqan, MD

Rebecca Gash, RN

John Hamm, MD

Sonia Carillo

Amy Weise, MD

Julie Burns

Manish Sharma, MD

Josh Settlemire, MSN

Ralph Hauke, MD

Alaina Randerson

Rachel Sanborn, MD

Starlee Hutchings

Elizabeth Davis, MD

Maritza Seanez

Haroutioun Shahinian, MD

Pablo Villarreal

Jonathan Lu, MD

Janice Alcaide, MD

Alexander Spira, MD

Colleen Cotter

Jonathan Thompson, MD

Josep Garcia, PhD

This is a Phase 1/2, open-label, non-randomized, 4-part Phase 1 trial to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of INBRX 106 administered as a single agent or in combination with the anti-PD-1 checkpoint inhibitor (CPI) pembrolizumab (Keytruda).

Part 4 NSCLC cohort is randomized 1;1:1, open-label

Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)

An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Multicohort, Phase 1/2 Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors

Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).

Tumor response will be determined by immune Response Evaluation Criteria in Solid Tumors (iRECIST).

Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0

Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-106 and INBRX-106 in combination with pembrolizumab

Area under the serum concentration time curve (AUC) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.

Maximum observed serum concentration (Cmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.

Trough observed serum concentration (Ctrough) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.

Time to Cmax (Tmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.

Frequency of anti-drug antibodies (ADA) against INBRX-106 as a single agent and in combination with pembrolizumab will be determined.

Merck Sharp & Dohme LLC

Inhibrx, Inc.

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Pharmaceutical Solutions

Micronutrients

Hematinics

Vitamins

Carboplatin

Dexamethasone

Pemetrexed

Cisplatin

Dexamethasone acetate

Folic Acid

Vitamin B Complex

Vitamin B 12

Hydroxocobalamin

Trace Elements

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Enzyme Inhibitors

Folic Acid Antagonists

Folinic Acid

Methylcobalamin

Folate

Vitamin B9

Vitamin B12

Cobalamin

Cyanocobalamin

Participants receive pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m\^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m\^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m\^2 IV Q3W until progression.

Participants receive saline placebo IV PLUS pemetrexed 500 mg/m\^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m\^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m\^2 IV Q3W until progression. With Amendment 10 (effective date: 23-Dec-2019), all participants will discontinue saline placebo. If documented progression occurs, participants may be able to receive pembrolizumab Q3W for the remainder of the study or until documented further progression.

Orally; at least 5 doses of folic acid must be taken during the 7 days preceding the first dose of pemetrexed, and folic acid dosing must continue during the full course of therapy and for 21 days after the last dose of pemetrexed.

Folic acid 350-1000 μg

Intramuscular injection in the week preceding the first dose of pemetrexed and once every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as pemetrexed administration.

Vitamin B12 1000 μg

For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.

Dexamethasone 4 mg

Saline solution

Medical Director

This is an efficacy and safety study of pembrolizumab (MK-3475) combined with pemetrexed/platinum chemotherapy versus pemetrexed/platinum chemotherapy alone in participants with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have not previously received systemic therapy for advanced disease. Participants will be randomly assigned to receive pembrolizumab combined with pemetrexed/platinum (Investigators choice of cisplatin or carboplatin), OR pemetrexed/platinum (Investigators choice of cisplatin or carboplatin).

With Amendment 10 (effective date 23-Dec-2019), active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded, and all participants in the 'control' arm will discontinue saline placebo.

With Amendment 11 (effective date 31-Jan-2022), once the study objectives have been met or the study has ended, participants will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment.

The primary hypothesis is that pembrolizumab in combination with pemetrexed/platinum chemotherapy prolongs Progression-Free Survival (PFS) and Overall Survival (OS) compared to pemetrexed/platinum chemotherapy alone.

Study of Pemetrexed+Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Participants With First Line Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-3475-189/KEYNOTE-189)

A Randomized, Double-Blind, Phase III Study of Platinum+Pemetrexed Chemotherapy With or Without Pembrolizumab (MK-3475) in First Line Metastatic Non-squamous Non-small Cell Lung Cancer Subjects (KEYNOTE-189)

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

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 is presented.

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS is presented.

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The percentage of participants who experienced a CR or PR is presented.

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. DOR assessments were based on blinded central imaging review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented.

An AE was defined as any untoward medical occurrence in a study participant administered study drug and which does not necessarily have to have a causal relationship with this study drug. For participants who switched from the Control group to receiving pembro, AEs that occurred after the first dose of pembro are excluded from this interim analysis, but will be included in the final analysis. The number of participants who experienced an AE is presented.

The number of participants who discontinued any randomized study drug due to an AE is presented.

Population: All participants receiving ≥1 dose of randomized study drug. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" \& "Disease progression" not related to study drug are excluded as AEs. For participants who switched from the Control group to receiving pembro, AEs occurring after 1st pembro dose are excluded from this interim analysis.

Participants received pembro 200 mg IV PLUS pemetrexed 500 mg/m\^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m\^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembro 200 mg IV PLUS pemetrexed 500 mg/m\^2 IV Q3W until progression.

Participants received saline placebo IV PLUS pemetrexed 500 mg/m\^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m\^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m\^2 IV Q3W until progression. With Amendment 10 (effective date: 23-Dec-2019), all participants will discontinue saline placebo. If documented progression occurred, participants may have been able to receive pembrolizumab Q3W for the remainder of the study or until documented further progression.

Control

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

TPS <1%

TPS ≥1%

Not Evaluable

Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue from an archival or newly obtained biopsy. Participants with a TPS ≥1% were classified as PD-L1 positive and participants with a TPS \<1% were classified as PD-L1 negative.

Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status

Participants were classified according to the type of platinum chemotherapy the Investigator chose for them to receive: Cisplatin or Carboplatin.

Platinum Chemotherapy

Never Smoker

Former/Current Smoker

Participants were classified according to their smoking status: Never Smoker or Former/Current Smoker.

Smoking Status

The Baseline Analysis Population consisted of all randomized participants.

Senior Vice President, Global Clinical Development

The analysis population consisted of all randomized participants.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)	NCT04198766	Solid Tumor Non-Small Cell ... Melanoma Head and Neck C... Gastric Cancer Renal Cell Carc... Urothelial Carc...	INBRX-106 - Hex... Pembrolizumab 2... Pembrolizumab 4...	18 Years -	Inhibrx, Inc.
Study of Pemetrexed+Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Participants With First Line Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-3475-189/KEYNOTE-189)	NCT02578680	Non-Small-Cell ...	Pembrolizumab 2... Cisplatin Carboplatin Pemetrexed Folic acid 350-... Vitamin B12 100... Dexamethasone 4... Saline solution	18 Years -	Merck Sharp & Dohme LLC
Study of Pemetrexed+Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Participants With First Line Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-3475-189/KEYNOTE-189)	NCT02578680	Non-Small-Cell ...	Pembrolizumab 2... Cisplatin Carboplatin Pemetrexed Folic acid 350-... Vitamin B12 100... Dexamethasone 4... Saline solution	18 Years -	Merck Sharp & Dohme LLC
Study of Pemetrexed+Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Participants With First Line Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-3475-189/KEYNOTE-189)-Japan Extension Study	NCT03950674	Non-Small-Cell ...	Pembrolizumab 2... Cisplatin Carboplatin Pemetrexed Folic acid 350-... Vitamin B12 100... Dexamethasone 4... Saline solution	18 Years -	Merck Sharp & Dohme LLC

Spots Global Cancer Trial Database for pembrolizumab 200 mg