Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Breast Neoplasms

Carcinoma, Squamous Cell

Pancreatic Neoplasms

Adenocarcinoma

Triple Negative Breast Neoplasms

Melanoma

Esophageal Squamous Cell Carcinoma

Colorectal Neoplasms

Neoplasms, Squamous Cell

Carcinoma

Breast Diseases

Skin Diseases

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Neoplasms, Glandular and Epithelial

Esophageal Neoplasms

Head and Neck Neoplasms

Esophageal Diseases

Pancreatic Cancer

Neuroendocrine Tumor

Neuroepithelioma

Esophageal Cancer

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

LGK974

Spartalizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Enzyme Inhibitors

PDR001

Novartis Pharmaceuticals

The primary purpose of this study is to find the recommended dose of LGK974 as a single agent and in combination with PDR001 that can be safely given to adult patients with selected solid malignancies that have progressed despite standard therapy or for which no effective standard therapy exists

This open-label multicenter phase 1 dose escalation study will be the first to administer LGK974 as a single agent or in combination with PDR001 in humans.

The study will comprise of 2 parts: a dose escalation of LGK974 as a single agent, followed by a safety expansion in specific disease indications; and a dose escalation of LGK974 in combination with PDR001, followed by a safety expansion in cutaneous melanoma.

A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands

A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands

Determine the Maximum Tolerated Dose (MTD) or Recommended Dose for Expansion (RDE) of LGK974 as a single agent and in combination with PDR001 when administered orally to adult patients with malignancies dependent on Wnt ligands.

The incidence of treatment-emergent adverse events (new or worsening from baseline) will be summarized by primary system organ class, severity based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, type of AE, relationship to study drug by dose group.

Evaluate pharmacokinetic (PK) parameters such as AUClast, AUCtau, Cmax, the apparent elimination T1/2 and Racc for LGK974 and its pharmacologically metabolite.

Assessing percent change from baseline to post-treatment of PD related to the Wnt pathway.

Patients with an Overall Response Rate(ORR), complete response (CR) or partial response (PR) rate and duration of response (DOR) assessed by RECIST 1.1 for single agent LGK974 and by RECIST1.1 and irRC for LGK974+PDR001.

Evaluate pharmacokinetic (PK) parameters such as AUClast, AUCtau, Cmax, the apparent elimination T1/2 and Racc for LGK974, its pharmacologically metabolite and PDR001.

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Prostatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Uterine Cervical Neoplasms

Endometrial Neoplasms

Urogenital Neoplasms

Genital Diseases

Urogenital Diseases

Endocrine Gland Neoplasms

Endocrine System Diseases

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Gonadal Disorders

Uterine Neoplasms

Uterine Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Coagulants

Antibodies

Hormones

Nivolumab

Immunoglobulins

Thromboplastin

Subjects (Cohort A) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.

The MTD or recommended dose from the dose-escalation stage may be further explored in subjects with non-small cell lung cancer \[NSCLC\] (Cohort B), epithelial ovarian cancer (Cohort D), cervical cancer (Cohort E), SCCHN (Cohort F), pancreatic cancer (Cohort G), Esophageal SCC (Cohort H), metastatic castration-resistant prostate cancer (Cohort I), triple-negative breast cancer (Cohort J), hormone-receptor positive breast cancer (Cohort K), endometrial cancer (Cohort L) and tumor agnostic tissue factor-expressing solid tumors (Cohort M).

Subjects (Cohort AN) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.

The MTD or recommended dose from the dose-escalation stage may be further explored in subjects with non-small cell lung cancer \[NSCLC\] (Cohort BN), SCCHN (Cohort FN), Esophageal SCC (Cohort HN).

XB002

Exelixis Clinical Trials

Backup or International

This is a Phase 1, open-label, multicenter, dose-escalation and expansion study evaluating the safety, tolerability, PK, pharmacodynamics, and clinical antitumor activity of XB002 administered IV q3w alone and in combination with nivolumab to subjects with advanced solid tumors.

Dose-escalation followed by cohort-expansion in tumor-specific expansion cohorts

Study of XB002 in Subjects With Solid Tumors (JEWEL-101)

A Dose-Escalation and Expansion Study of the Safety and Pharmacokinetics of XB002 as Single-Agent and Combination Therapy in Subjects With Inoperable Locally Advanced or Metastatic Solid Tumors

To determine the MTD and/or RD for further evaluation of IV administration of XB002 alone and in combination therapy in subjects with advanced malignancies

To evaluate preliminary efficacy of XB002 when administered alone and in combination therapy by determining the ORR per RECIST 1.1 (or other applicable response criteria eg. RANO or PCWG3 criteria) as assessed by the Investigator

To evaluate the safety of XB002 through the evaluation of incidence and severity of nonserious adverse events (AEs) and serious adverse events (SAEs)

To evaluate the tolerability of XB002 through the evaluation of duration of exposure for the study treatment

To evaluate the tolerability of XB002 through the evaluation of dose intensity of the study treatment

To evaluate the Cmax for XB002, total antibody, and free payload at scheduled visits over time

To evaluate the Ctrough of XB002, total antibody, and free payload at scheduled visits over time

To assess the immunogenicity of XB002 as measured by anti-drug antibody (ADA) analysis

To evaluate the anti-tumor activity of XB002, as measured by ORR, per RECIST 1.1 (or other applicable response criteria eg. RANO or PCWG3 criteria) as assessed by the Investigator (dose escalation stage) or by a BIRC for selected cohorts (cohort expansion stage).

To evaluate the anti-tumor activity of XB002, as measured by DOR, per RECIST 1.1 (or other applicable response criteria eg. RANO or PCWG3 criteria) as assessed by the Investigator (dose escalation stage) or by a BIRC for selected cohorts (cohort expansion stage)

To evaluate the anti-tumor activity of XB002, as measured by PFS, per RECIST 1.1 (or other applicable response criteria eg. RANO or PCWG3 criteria) as assessed by the Investigator (dose escalation stage) or by a BIRC for selected cohorts (cohort expansion stage)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands	NCT01351103	Pancreatic Canc... BRAF Mutant Col... Melanoma Triple Negative... Head and Neck S... Cervical Squamo... Esophageal Squa... Lung Squamous C...	LGK974 PDR001	18 Years -	Novartis
Study of XB002 in Subjects With Solid Tumors (JEWEL-101)	NCT04925284	Non Small Cell ... Cervical Cancer SCCHN Pancreatic Canc... Esophageal SCC Metastatic Cast... Triple Negative... Hormone Recepto... Epithelial Ovar... Endometrial Can... Tissue Factor-E...	XB002 Nivolumab	18 Years -	Exelixis
A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands	NCT01351103	Pancreatic Canc... BRAF Mutant Col... Melanoma Triple Negative... Head and Neck S... Cervical Squamo... Esophageal Squa... Lung Squamous C...	LGK974 PDR001	18 Years -	Novartis

Spots Global Cancer Trial Database for esophageal scc