Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Breast Neoplasms

Prostatic Neoplasms

Carcinoma

Carcinoma, Squamous Cell

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Triple Negative Breast Neoplasms

Melanoma

Carcinoma, Renal Cell

Carcinoma, Transitional Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urogenital Neoplasms

Genital Diseases

Urogenital Diseases

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

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Endocrine System Diseases

Gonadal Disorders

Breast Diseases

Head and Neck Neoplasms

Ovarian Cancer

Ovarian Epithelial Cancer

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Transitional Cell Carcinoma

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Pembrolizumab

Antibodies, Bispecific

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

XmAb®808 in combination with pembrolizumab

XmAb®808

Keytruda® (pembrolizumab)

Michael Chiarella

Amber Sarot

Chet Bohac, MD

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of intravenous (IV) administration of XmAb808 in combination with pembrolizumab in subjects with selected advanced solid tumors and to identify the minimum safe and biologically effective/recommended dose (RD) and schedule for XmAb808.

This is a Phase 1, open-label, first-in-human (FIH), multiple-dose, dose escalation study with cohort expansion at the RD, designed to evaluate the safety and tolerability of XmAb808 in combination with pembrolizumab. This study will be conducted in 2 parts: Part A (dose escalation) and Part B (cohort expansion).

Phase 1, First-in-human, Dose-finding and Expansion Study to Evaluate XmAb®808 in Combination With Pembrolizumab in Advanced Solid Tumors

A Phase 1, First-in-Human, Dose-Finding and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of XmAb®808 in Combination With Pembrolizumab in Selected Advanced Solid Tumors

Safety and tolerability as assessed by incidence of TEAEs, including clinically significant changes in safety laboratory tests and clinical findings

Safety and tolerability as assessed by incidence of DLTs and all available data which will be used to determine the optimal dose regimen

Area under the plasma concentration versus time curve (AUCtau)

Objective response rate by RECIST 1.1 assessment of CT/MRI imaging, as modified by PCWG3 for participants with prostate cancer

Progression-free survival by RECIST 1.1 assessment of CT/MRI imaging, as modified by PCWG3 for participants with prostate cancer

Duration of Response by RECIST 1.1 assessment of CT/MRI imaging, as modified by PCWG3 for participants with prostate cancer

Xencor, Inc.

Kidney Neoplasms

Adenocarcinoma

Urologic Neoplasms

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Bone Density Conservation Agents

Micronutrients

Vitamins

Vitamin D

Cholecalciferol

Calcium

Calcium, Dietary

Denosumab

Vitamin D3

Calciferol

Pembrolizumab 200 mg IV every 3 weeks plus denosumab 120 mg SC on day 1, 8, 22 and then every 3 weeks with daily oral calcium and vitamin D, continued until disease progression or prohibitive toxicity

Pembrolizumab 200 mg IV every 3 weeks plus denosumab 120 mg SC on day 1, 8, 22 and then every 3 weeks with daily oral calcium and vitamin D

Pembrolizumab plus denosumab

This Single-arm, multicentre, phase 2 trial aims determine the activity and safety of pembrolizumab and denosumab in advanced clear cell renal cell carcinoma (ccRCC).

Renal cell carcinoma (RCC) is the 9th most common cancer in Australia, the 10th most common cancer in Western populations1. Approximately 75% of kidney cancers are clear-cell renal cell carcinomas (ccRCC). Current treatments for metastatic ccRCC include VEGFR tyrosine kinase inhibitors (TKIs) and mTOR inhibitors and while many patients benefit from first-line VEGFR TKIs, progression is inevitable and these treatments remain palliative. Second-line VEGFR TKIs and mTOR inhibitors have some benefit but in a smaller increment than first-line treatment. ccRCC is highly immunogenic with benefit from adjuvant autologous vaccines, high-dose IL2 in selected patients and spontaneous remissions seen in a fraction of patients. Cytokine immunotherapy delivered durable complete responses in a subset of patients who survived the very high toxicity of these agents, but use of cytokine immunotherapy is uncommon in modern practice.

Preclinical data and case reports suggest that denosumab, an inhibitor of RANKL signalling, might potentiate the anti-tumour effects of immunotherapy with pembrolizumab, an antibody directed against PD-1, without overlapping toxicities.

This study aims to determine the activity and safety of pembrolizumab and denosumab in advanced clear cell renal cell carcinoma (ccRCC), in patients with disease progression during or after VEGFR TKI treatment.

Adults with unresectable or metastatic ccRCC progressing after treatment with a VEGFR TKI. Key eligibility criteria include target lesion(s) according to RECIST 1.1, good performance status (ECOG PS 0-2), no history of significant autoimmune disease, tumour sample available (archival or recent biopsy), and no previous treatment with immunotherapy.

All participants will receive the study interventions of pembrolizumab and denosumab. All participants will receive the study interventions of pembrolizumab and denosumab. Pembrolizumab will be given every 3 weeks at a dose of 200mg and denosumab will be given on day 1, day 8, day 22 and then every 21 days (3 weekly) thereafter as a single subcutaneous injection. Treatment with pembrolizumab and denosumab will continue until evidence of clinical progression or prohibitive toxicity, or withdrawal of consent, up to a maximum duration of 2 years.

70 eligible participants will be recruited from 15 sites in Australia and New Zealand over a 2 year period.

Denosumab and Pembrolizumab in Clear Cell Renal Carcinoma

Denosumab and Pembrolizumab in Clear Cell Renal Carcinoma: a Phase II Trial (ANZUP 1601)

All IPD that underlie results in a publication

Identifying tissue and circulating biomarkers that are prognostic and predictive of response to treatment, safety and resistance to study treatment (associations of biomarkers with clinical outcomes).

The objective tumour response rate, as assessed by RECIST1.1 - This is defined as the proportion of participants in the analysis set with a confirmed complete response (CR) or partial response (PR) divided by the number of participants in the analysis set.

Progression-free survival is defined as proportion alive and progression-free at 6 months, RECIST 1.1, iRECIST

Disease control rate is defined the proportion in CR, PR, or SD at 6 months iRECIST) rate (DCRR)

Objective tumour response is defined as duration of OTR using RECIST 1.1 and iRECIST

This is defined as the interval from date of registration to the date of first evidence of first skeletal related event.

The number of patients with adverse events, particularly immune-related adverse events, that are related to study drug, as assessed and graded according to CTCAE v4.03

The number of participants with permanent discontinuation of treatment or delays due to toxicity, as assessed and graded according to CTCAE v4.03

Merck Sharp & Dohme LLC

Amgen

Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 1, First-in-human, Dose-finding and Expansion Study to Evaluate XmAb®808 in Combination With Pembrolizumab in Advanced Solid Tumors	NCT05585034	Head and Neck S... Melanoma Exclud... Non-small Cell ... Urothelial Carc... Renal Cell Carc... Castration-resi... Ovarian Cancer,... TNBC - Triple-N... Colorectal Canc...	XmAb®808 Keytruda® (pemb...	18 Years -	Xencor, Inc.
Denosumab and Pembrolizumab in Clear Cell Renal Carcinoma	NCT03280667	Renal Cell Carc... Metastatic Kidn...	Pembrolizumab p...	18 Years -	Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Denosumab and Pembrolizumab in Clear Cell Renal Carcinoma	NCT03280667	Renal Cell Carc... Metastatic Kidn...	Pembrolizumab p...	18 Years -	Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Spots Global Cancer Trial Database for renal cell carcinoma, clear cell