Clinical trial NCT04215978: Safety and Preliminary Effectiveness of BGB-A445 in Combination With Tislelizumab in Participants With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Solid Tumor
Non Small Cell Lung Cancer
Head and Neck Squamous Cell Carcinoma (HNSCC)
Nasopharyngeal Carcinoma (NPC)
Keywords: OX40
PD-1
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2020-01-02
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1a: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
measure: Phase 1a: Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
measure: Phase 1a: Number of Participants Experiencing AEs meeting protocol defined Dose-Limiting Toxicity (DLT) criteria
timeFrame: Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
measure: Phase 1a: Maximum Tolerated Dose (MTD) of BGB-A445
timeFrame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
measure: Phase 1b: RP2D of BGB-A445 when Administered Alone
timeFrame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
measure: Phase 1b: Overall Response Rate (ORR) as Assessed by the Investigator
timeFrame: 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 outcomes:
measure: Phase 1a: Overall Response Rate (ORR) as Assessed by the Investigator
timeFrame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
measure: Phase 1a: Duration of Response (DOR) as Assessed by the Investigator
timeFrame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
measure: Phase 1a: Disease-Control Rate (DCR) as Assessed by the Investigator
timeFrame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
measure: Phase 1a: Serum Concentration of BGB-A445
timeFrame: 60 minutes predose up to 72 hours postdose
measure: Phase 1a: Serum Concentration of tislelizumab
timeFrame: 60 minutes predose up to 72 hours postdose
measure: Phase 1a: Maximum Observed Plasma Concentration (Cmax) of BGB-A445
timeFrame: 60 minutes predose up to 72 hours postdose
measure: Phase 1a: Maximum Observed Plasma Concentration (Cmax) of tislelizumab
timeFrame: 60 minutes predose up to 72 hours postdose
measure: Phase 1a: Minimum Observed Plasma Concentration (Cmin) of BGB-A445
timeFrame: 60 minutes predose up to 72 hours postdose
measure: Phase 1a: Minimum Observed Plasma Concentration (Cmin) of tislelizumab
timeFrame: 60 minutes predose up to 72 hours postdose
measure: Phase 1a: Time to Maximum Plasma Concentration (Tmax) of BGB-A445
timeFrame: 60 minutes predose up to 72 hours postdose
measure: Phase 1a: Time to Maximum Plasma Concentration (Tmax) of tislelizumab
timeFrame: 60 minutes predose up to 72 hours postdose
measure: Phase 1a: Area Under the Concentration-Time Curve of 0-21 Days (AUC0-21d) of BGB-A445
timeFrame: 60 minutes predose up to 21 days postdose
measure: Phase 1a: Immunogenic Responses to BGB-A445 as assessed through the detection of antidrug antibodies
timeFrame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
measure: Phase 1a: Immunogenic Responses to tislelizumab as assessed through the detection of antidrug antibodies
timeFrame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
measure: Phase 1b: Progression-free survival (PFS) as Assessed by the Investigator
timeFrame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
measure: Phase 1b: Duration of Response (DOR) as Assessed by the Investigator
timeFrame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
measure: Phase 1b: Disease-Control Rate (DCR) as Assessed by the Investigator
timeFrame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
measure: Phase 1b: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
measure: Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
measure: Phase 1b: Serum Concentration of BGB-A445
timeFrame: 60 minutes predose up to 72 hours postdose
measure: Phase 1b: Maximum Observed Plasma Concentration (Cmax) of BGB-A445
timeFrame: 60 minutes predose up to 72 hours postdose
measure: Phase 1b: Minimum Observed Plasma Concentration (Cmin) of BGB-A445
timeFrame: 60 minutes predose up to 72 hours postdose
measure: Phase 1b: Time to Maximum Plasma Concentration (Tmax) of BGB-A445
timeFrame: 60 minutes predose up to 72 hours postdose
measure: Phase 1b: Area Under the Concentration-Time Curve of 0-21 Days (AUC0-21d) of BGB-A445
timeFrame: 60 minutes predose up to 21 days postdose
measure: Phase 1b: Immunogenic Responses to BGB-A445 as assessed through the detection of antidrug antibodies
timeFrame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Valkyrie Clinical Trials
state: California
city: San Diego
country: United States
facility: California Cancer Associates for Research & Excellence (cCARE)
state: California
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center (Univ Of Pittsburgh)
state: Pennsylvania
city: Blacktown
country: Australia
facility: Blacktown Cancer And Haematology Centre
state: New South Wales
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: Nucleus Network
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Wuhan
country: China
facility: Union Hospital Of Tongji Medical College, Huazhong University Of Science And Technology
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital Of Central South University
state: Hunan
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital Of Fudan University
state: Shanghai
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center (NCC)
state: Gyeonggi-do
city: Gyeonggido
country: Korea, Republic of
facility: Cha Bundang Medical Center, Cha University
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
state: Gyeonggi-do
city: Seongnamsi
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya Medical Centre
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
state: NAP
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital (Chulalongkorn University)
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital Mahidol University
city: Muang
country: Thailand
facility: Srinagarind Hospital (Khon Kaen University)
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: