Study of Safety and Efficacy of DKY709 Alone or in Combination With PDR001 in Patients With Advanced Solid Tumors.

Phase 1

Active, not recruiting

• Conditions: Nasopharyngeal Carcinoma; Microsatellite Stable Colorectal Cancer; Carcinoma, Non-Small-Cell Lung; Melanoma; Triple Negative Breast Cancer
• Interventions: Drug: DKY709; Drug: PDR001

• Registration Number: NCT03891953
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This is a phase I/Ib, open label study. The escalation portion will characterize the safety and tolerability of DKY709 and DKY709 in combination with PDR001 in subjects with NSCLC or melanoma who have received prior anti-PD-1/PD-L1 therapy, or subjects with NPC. After the determination of the MTD/RD for a particular treatment arm, dose expansion will further assess safety, tolerability, PK/PD, and anti-tumor activity of each regimen at the MTD/RD.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-03-26
• Study First Submitted QC: 2019-03-26
• Study First Posted: 2019-03-27
• Study Start: 2019-05-07
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-09
• Last Update Posted: 2025-01-10
• Primary Completion: 2025-02-28
• Study Completion: 2025-02-28

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 99

Inclusion Criteria

1. Signed informed consent must be obtained prior to participation in the study.

2. Patients must be ≥18 years of age at the time of informed consent form (ICF) signature.

3. Patients with advanced/metastatic cancer who have progressed despite having received standard therapy in the metastatic setting or are intolerant to standard therapy, and for whom no effective standard therapy is available

4. In expansion: patient with measurable disease as determined by RECIST version 1.1,

5. Dose escalation, patients must fit into one of the following groups:

   • NSCLC, previously treated with an anti-PD-1/PD-L1 therapy
   • Cutaneous Melanoma, previously treated with an anti-PD-1/PD-L1 therapy
   • NPC

   Dose expansion part, patients must fit into one of the following groups:

   • NSCLC with historic documentation of PD-L1 ≥ 1%. Patients must have progressive disease after having experienced at least 4 months of investigator-assessed disease stability or response on prior anti-PD-L1-containing therapy
   • Cutaneous Melanoma, previously treated with anit-PD-1/PD-L1 therapy. Patients should have documented progression following anti-PD-1/PD-L1 therapy.
   • NPC, naive to anti-PD-1/PD-L1 therapy
   • mssCRC, naive to anti-PD-1/PD-L1 therapy
   • TNBC, naive to anti-PD-1/PD-L1 therapy

6. ECOG Performance Status ≤ 1

7. Patients must have a site of disease amenable to core needle biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patients must be willing to undergo a new tumor biopsy at baseline, and during therapy on the study. Exceptions may be considered after documented discussion with Novartis.

Read More

Exclusion Criteria

1. Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within 2 weeks prior to study entry. Patients with treated brain metastases should be neurologically stable for at least 4 weeks prior to study entry and off steroids for at least 2 weeks before administration of any study treatment.

2. History of severe hypersensitivity reactions to any ingredient of study drug(s) or other mAbs and/or their excipients.

3. Patient with out of range laboratory values defined as:

   • Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 40 mL/min
   • Total bilirubin > 1.5 x ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
   • Alanine aminotransferase (ALT) > 3 x ULN, except for patients that have tumor involvement of the liver, who are excluded if ALT > 5 x ULN
   • Aspartate aminotransferase (AST) > 3 x ULN, except for patients that have tumor involvement of the liver, who are excluded if AST > 5 x ULN
   • Absolute neutrophil count (ANC) < 1.0 x 109/L
   • Platelet count < 75 x 109/L (growth factor or transfusion support may not be used to meet entry criterion)
   • Hemoglobin (Hgb) < 8 g/dL (growth factor or transfusion support may not be used to meet entry criterion)
   • Magnesium, calcium or phosphate abnormality CTCAE > grade 1
   • Potassium abnormality CTCAE ≥ grade 1; supplementation to meet eligibility criteria is acceptable

4. Clinically significant cardiac disease or impaired cardiac function, including any of the following:

   • Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA grade ≥ 2), uncontrolled hypertension or clinically significant arrhythmia
   • On screening: QTcF > 450 msec (male), or > 460 msec (female)
   • QTc not assessable
   • Congenital long QT syndrome
   • History of familial long QT syndrome or known family history of as Torsades de Pointes
   • Acute myocardial infarction or unstable angina pectoris < 3 months prior to study entry

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DKY709	DKY709	DKY709 monotherapy
DKY709 + PDR001	DKY709	Combination therapy with DKY709 and PDR001
DKY709 + PDR001	PDR001	Combination therapy with DKY709 and PDR001

Primary Outcome Measures

Name	Time	Method
incidence of Dose Limiting Toxicities (DLTs)	1 Month	The incidence of DLTs during the first cycle of treatment with single agent DKY709 or the combination of DKY709 with PDR001.
Safety of DKY709 single agent treatment or DKY709 in combination with PDR001.	24 months	Incidence and severity of AEs and SAEs
Tolerability of DKY709 single agent treatment or DKY709 in combination with PDR001.	24 months	Incidence and severity of AEs and SAEs

Secondary Outcome Measures

Name	Time	Method
AUC of DKY709 and PDR001	24 months	AUC
Best Overall Response (BOR)	24 months	Determine BOR in each part of the study
Cmax of DKY709 and PDR001	24 months	Cmax
Tmax of DKY709 and PDR001	24 months	Tmax
Half-life of DKY709 and PDR001	24 months	Half-life
Progression Free Survival (PFS)	24 months	Determine PFS in each part of the study
Duration of Response (DOR)	24 months	Determine DOR in each part of the study
Time to Progression (TTP)	24 months	Determine TTP in each part of the study

Trial Locations

Locations (4)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

Novartis Investigative Site; 🇨🇳 Taipei, Taiwan