Safety and Preliminary Effectiveness of BGB-A445 in Combination With Tislelizumab in Participants With Advanced Solid Tumors

Non Small Cell Lung Cancer Clinical Trial

Official title:

Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of the Anti OX40 Agonist Monoclonal Antibody BGB-A445 in Combination With the Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04215978
• Other study ID #: BGB-A317-A445-101
• Secondary ID: 2022-501177-39-0
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 30, 2020
• Est. completion date: September 16, 2024

Study information

• Verified date: May 2024
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and tolerability of BGB-A445 alone and in combination with tislelizumab in participants with advanced solid tumors; and to determine the maximum tolerated dose(s) (MTD) or maximum administered dose(s) (MAD) and recommended Phase 2 doses (RP2D) of BGB-A445 alone and in combination with tislelizumab.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 203
• Est. completion date: September 16, 2024
• Est. primary completion date: September 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Phase 1a (dose escalation): Participants with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors who have previously received standard systemic therapy or for whom treatment is not available, not tolerated or refused.

1. Enrollment will be limited to participants with advanced solid tumors for which there is clinical evidence of response to T cell based immuno-oncology agents (eg, anti PD 1) or other scientific evidence in support of an immunologically sensitive tumor type.

2. Participant has not received prior therapy targeting OX40 or any other T cell agonist therapy (prior checkpoint inhibitor therapy is allowed)

2. Phase 1b, the dose expansion phase, aims to include participants in specific tumor type cohorts who do not have access to standard systemic treatment, cannot tolerate it, or it is deemed inappropriate by the investigator. Cohort 1 focuses on non-small cell lung cancer (NSCLC) patients with advanced or metastatic disease, while Cohort 2 involves individuals with recurrent or metastatic head and neck squamous cell cancer (HNSCC). Cohort 3 includes participants with nasopharyngeal carcinoma (NPC), and Cohort 4 is for NSCLC patients with PD-L1 expression of at least 50%. Each cohort has specific eligibility criteria related to prior therapies, tumor characteristics, and treatment-free intervals.

3. Has at least 1 measurable lesion as defined per RECIST 1.1. The target lesion(s) selected have not been previously treated with local therapy OR the target lesion(s) selected that are within the field of prior local therapy have subsequently progressed as defined by RECIST 1.1 4. Participants should be able to provide tumor tissue sample

5. Eastern Cooperative Oncology Group (ECOG) Performance Status = 1 and a life expectancy of = 6 months.

6. Adequate organ function as indicated by the following laboratory values up to first dose of study drug a. Participants must not have required blood transfusion or growth factor support = 14 days

before sample collection for the following:

• Absolute neutrophil count = 1.5 x 10^9/L
• Platelet count = 75 x 10^9/L
• Hemoglobin = 90 g/L b. Estimated glomerular filtration rate (GFR) = 60 mL/min/1.73 m^2 determined by the Cockcroft-Gault formula without correction for body surface area (BSA)
• The estimated GFR for participants with renal cell carcinoma must be = 30 mL/min/1.73 m^2 by the Cockcroft-Gault formula c. Serum total bilirubin = 1.5 x ULN (< 3 x ULN for participants with Gilbert syndrome) d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x ULN;
• = 5 x ULN for participants with hepatocellular carcinoma or liver metastases

Key Exclusion Criteria:

1. Active leptomeningeal disease or uncontrolled brain metastasis. Participants with equivocal findings or with confirmed brain metastases are eligible for enrollment provided they are asymptomatic and radiologically stable without the need for corticosteroid treatment for at least 4 weeks prior to the first dose of study drug(s)

2. Active autoimmune diseases or history of autoimmune diseases that may relapse or history of life-threatening toxicity related to prior immune therapy, with the

following exceptions:

1. Controlled type 1 diabetes

2. Hypothyroidism (provided it is managed with hormone-replacement therapy only)

3. Controlled celiac disease

4. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or alopecia)

5. Any other disease that is not expected to recur in the absence of external triggering factors (requires consultation with the medical monitor prior to enrollment)

3. Any active malignancy = 2 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast)

4. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication = 14 days

before the first dose of study drug(s), with the following exceptions:

1. Adrenal replacement steroid (dose = 10 mg daily of prednisone or equivalent)

2. Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption

3. Short course (= 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a nonautoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen)

5. Any major surgical procedure occurring = 28 days before the first dose of study drug(s). If surgical procedure occurs > 28 days, they must have recovered adequately from the toxicity NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Carcinoma
• Head and Neck Squamous Cell Carcinoma (HNSCC)
• Nasopharyngeal Carcinoma
• Nasopharyngeal Carcinoma (NPC)
• Non Small Cell Lung Cancer
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• BGB-A445
Administered as specified in the treatment arm
• tislelizumab
Administered as specified in the treatment arm

Locations

Country	Name	City	State
Australia	Pindara Private Hospital	Benowa	Queensland
Australia	Blacktown Cancer and Haematology Centre	Blacktown	New South Wales
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Monash Health	Clayton	Victoria
Australia	Peter Maccallum Cancer Centre	Melbourne	Victoria
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Korea, Republic of	National Cancer Center	Goyangsi	Gyeonggido
Korea, Republic of	Cha Bundang Medical Center, Cha University	Gyeonggido
Korea, Republic of	Seoul National University Bundang Hospital	Seongnamsi	Gyeonggido
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Ajou University Hospital	Suwonsi	Gyeonggido
Korea, Republic of	The Catholic University of Korea, St Vincents Hospital	Suwonsi	Gyeonggido
Malaysia	Universiti Kebangsaan Malaysia Medical Centre (Ukmmc)	Kuala Lumpur
New Zealand	Auckland City Hospital	Auckland
Thailand	Maharaj Nakorn Chiang Mai Hospital (Chiang Mai University)	Muang
Thailand	Sunpasitthiprasong Hospital	Mueang
United States	California Cancer Associates For Research and Excellence, Ccare Encinitas	Encinitas	California
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Valkyrie Clinical Trials	Los Angeles	California
United States	Upmc Hillman Cancer Center(Univ of Pittsburgh)	Pittsburgh	Pennsylvania
United States	California Cancer Associates For Research and Excellence, Inc	San Marcos	California
United States	Summit Cancer Centers	Spokane Valley	Washington

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Korea, Republic of,  Malaysia,  New Zealand,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1a: Number of Participants Experiencing Adverse Events (AEs)		Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
Primary	Phase 1a: Number of Participants Experiencing Serious Adverse Events (SAEs)		Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
Primary	Phase 1a: Number of Participants Experiencing AEs meeting protocol defined Dose-Limiting Toxicity (DLT) criteria		Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
Primary	Phase 1a: Maximum Tolerated Dose (MTD) of BGB-A445	The MTD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30%	Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Primary	Phase 1b: RP2D of BGB-A445 when Administered Alone		Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Primary	Phase 1b: Overall Response Rate (ORR) as Assessed by the Investigator	ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR)	Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary	Phase 1a: Overall Response Rate (ORR) as Assessed by the Investigator		Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary	Phase 1a: Duration of Response (DOR) as Assessed by the Investigator		Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary	Phase 1a: Disease-Control Rate (DCR) as Assessed by the Investigator		Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary	Phase 1a: Serum Concentration of BGB-A445		60 minutes predose up to 72 hours postdose
Secondary	Phase 1a: Serum Concentration of tislelizumab		60 minutes predose up to 72 hours postdose
Secondary	Phase 1a: Maximum Observed Plasma Concentration (Cmax) of BGB-A445		60 minutes predose up to 72 hours postdose
Secondary	Phase 1a: Maximum Observed Plasma Concentration (Cmax) of tislelizumab		60 minutes predose up to 72 hours postdose
Secondary	Phase 1a: Minimum Observed Plasma Concentration (Cmin) of BGB-A445		60 minutes predose up to 72 hours postdose
Secondary	Phase 1a: Minimum Observed Plasma Concentration (Cmin) of tislelizumab		60 minutes predose up to 72 hours postdose
Secondary	Phase 1a: Time to Maximum Plasma Concentration (Tmax) of BGB-A445		60 minutes predose up to 72 hours postdose
Secondary	Phase 1a: Time to Maximum Plasma Concentration (Tmax) of tislelizumab		60 minutes predose up to 72 hours postdose
Secondary	Phase 1a: Area Under the Concentration-Time Curve of 0-21 Days (AUC0-21d) of BGB-A445		60 minutes predose up to 21 days postdose
Secondary	Phase 1a: Immunogenic Responses to BGB-A445 as assessed through the detection of antidrug antibodies		Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary	Phase 1a: Immunogenic Responses to tislelizumab as assessed through the detection of antidrug antibodies		Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary	Phase 1b: Progression-free survival (PFS) as Assessed by the Investigator	Determined from investigator derived tumor assessments as per RECIST 1.1	Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary	Phase 1b: Duration of Response (DOR) as Assessed by the Investigator		Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary	Phase 1b: Disease-Control Rate (DCR) as Assessed by the Investigator		Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary	Phase 1b: Number of Participants Experiencing Adverse Events (AEs)		Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
Secondary	Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs)		Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
Secondary	Phase 1b: Serum Concentration of BGB-A445		60 minutes predose up to 72 hours postdose
Secondary	Phase 1b: Maximum Observed Plasma Concentration (Cmax) of BGB-A445		60 minutes predose up to 72 hours postdose
Secondary	Phase 1b: Minimum Observed Plasma Concentration (Cmin) of BGB-A445		60 minutes predose up to 72 hours postdose
Secondary	Phase 1b: Time to Maximum Plasma Concentration (Tmax) of BGB-A445		60 minutes predose up to 72 hours postdose
Secondary	Phase 1b: Area Under the Concentration-Time Curve of 0-21 Days (AUC0-21d) of BGB-A445		60 minutes predose up to 21 days postdose
Secondary	Phase 1b: Immunogenic Responses to BGB-A445 as assessed through the detection of antidrug antibodies		Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first