A Phase 1b, Multicenter, Open-Label Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-368 Plus Tilsotolimod and Other Therapy Combinations in Subjects With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 30
- Locations
- 26
- Primary Endpoint
- Time to Maximum Serum Concentration (Tmax) of ABBV-368
Study Overview
Brief Summary
The main objective of this study is to assess safety, tolerability, and pharmacokinetics (PK) of ABBV-368 plus tilsotolimod; ABBV-368 plus tilsotolimod and nab-paclitaxel; and ABBV-368 plus tilsotolimod, nab-paclitaxel, and ABBV-181 in participants with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participants should weigh at least 35 kg.
- •Eastern Cooperative Oncology Group performance status of 0 or 1 and a life expectancy of >= 3 months.
- •Participant have >= 1 lesion accessible for intratumoral injection.
- •Histologically or cytologically confirmed R/M HNSCC (of the following 4 subsites: oral cavity, oropharynx, larynx, and hypopharynx) who previously progressed either during or after <= 3 prior treatment regimens administered in the recurrent or metastatic setting.
- •Must have received 1 immunotherapy regimen which included a PD-(L)1 inhibitor.
- •Must have received platinum-based therapy, or be considered ineligible for platinum-based therapy by the investigator.
Exclusion Criteria
- •Uncontrolled metastases to the central nervous system (CNS).
- •Participants with brain metastases are eligible provided that evidence of clinical and radiographic stable disease for at least 4 weeks after definitive therapy is given and participants have not used prohibited levels of steroids for at least 4 weeks prior to first dose of the study.
- •Received prior treatment with OX40 or toll-like receptor (TLR) agonists (excluding topical agents).
Arms & Interventions
Arm 1: ABBV-368 + Tilsotolimod
Participants will be administered ABBV-368 and Tilsotolimod at various timepoints as described in the protocol.
Intervention: ABBV-368 (Drug)
Arm 1: ABBV-368 + Tilsotolimod
Participants will be administered ABBV-368 and Tilsotolimod at various timepoints as described in the protocol.
Intervention: Tilsotolimod (Drug)
Arm 2: ABBV-368 + Tilsotolimod + Nab-paclitaxel
Participants will be administered ABBV-368, Tilsotolimod and Nab-paclitaxel at various timepoints as described in the protocol.
Intervention: ABBV-368 (Drug)
Arm 2: ABBV-368 + Tilsotolimod + Nab-paclitaxel
Participants will be administered ABBV-368, Tilsotolimod and Nab-paclitaxel at various timepoints as described in the protocol.
Intervention: Tilsotolimod (Drug)
Arm 2: ABBV-368 + Tilsotolimod + Nab-paclitaxel
Participants will be administered ABBV-368, Tilsotolimod and Nab-paclitaxel at various timepoints as described in the protocol.
Intervention: Nab-paclitaxel (Drug)
Arm 3: ABBV-368 + Tilsotolimod + Nab-paclitaxel + ABBV-181
Participants will be administered ABBV-368, Tilsotolimod, Nab-paclitaxel and ABBV-181 at various timepoints as described in the protocol.
Intervention: ABBV-368 (Drug)
Arm 3: ABBV-368 + Tilsotolimod + Nab-paclitaxel + ABBV-181
Participants will be administered ABBV-368, Tilsotolimod, Nab-paclitaxel and ABBV-181 at various timepoints as described in the protocol.
Intervention: Tilsotolimod (Drug)
Arm 3: ABBV-368 + Tilsotolimod + Nab-paclitaxel + ABBV-181
Participants will be administered ABBV-368, Tilsotolimod, Nab-paclitaxel and ABBV-181 at various timepoints as described in the protocol.
Intervention: Nab-paclitaxel (Drug)
Arm 3: ABBV-368 + Tilsotolimod + Nab-paclitaxel + ABBV-181
Participants will be administered ABBV-368, Tilsotolimod, Nab-paclitaxel and ABBV-181 at various timepoints as described in the protocol.
Intervention: ABBV-181 (Drug)
Outcomes
Primary Outcomes
Time to Maximum Serum Concentration (Tmax) of ABBV-368
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Time to Maximum Serum Concentration (Tmax) of ABBV-368
Change in Clinical Laboratory Test Results
Time Frame: Up to approximately 2 years following the first dose
Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.
Area Under Plasma Concentration-Time Curve of Tilsotolimod From Time 0 to the Time of Last Measurable Concentration (AUCt)
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Area Under Plasma Concentration-Time Curve of Tilsotolimod From Time 0 to the Time of Last Measurable Concentration (AUCt)
Maximum Observed Serum Concentration (Cmax) of ABBV-181 (Arm 3 Only)
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Maximum Observed Serum Concentration (Cmax) of ABBV-181
Change in Vital Signs
Time Frame: Up to approximately 2 years following the first dose
Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.
Terminal-Phase Elimination Rate Constant (β) of ABBV-368
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Terminal-Phase Elimination Rate Constant (β) of ABBV-368
Terminal-Phase Elimination Rate Constant (β) of Tilsotolimod
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Terminal-Phase Elimination Rate Constant (β) of Tilsotolimod
Terminal Half-Life (t1/2) of Tilsotolimod
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Terminal Half-Life (t1/2) of Tilsotolimod
Area Under Serum Concentration-Time Curve of ABBV-181 From Time 0 to the Time of Last Measurable Concentration (AUCt) (Arm 3 Only)
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Area Under Serum Concentration-Time Curve of ABBV-181 From Time 0 to the Time of Last Measurable Concentration (AUCt)
Terminal-Phase Elimination Rate Constant (β) of ABBV-181 (Arm 3 Only)
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Terminal-Phase Elimination Rate Constant (β) of ABBV-181
Terminal Half-Life (t1/2) of ABBV-181 (Arm 3 Only)
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Terminal Half-Life (t1/2) of ABBV-181
Area Under Serum Concentration-Time Curve of ABBV-368 From Time 0 to the Time of Last Measurable Concentration (AUCt)
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Area Under Serum Concentration-Time Curve of ABBV-368 From Time 0 to the Time of Last Measurable Concentration (AUCt)
Maximum Plasma Concentration (Cmax) of Tilsotolimod
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Maximum Observed Plasma Concentration (Cmax) of Tilsotolimod
Time to Maximum Plasma Concentration (Tmax) of Tilsotolimod
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Time to Maximum Plasma Concentration (Tmax) of Tilsotolimod
Number of Participants with Adverse Events (AEs)
Time Frame: Up to approximately 2 years following the first dose
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study.
Maximum Observed Serum Concentration (Cmax) of ABBV-368
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Maximum Serum Concentration (Cmax) of ABBV-368
Terminal Half-Life (t1/2) of ABBV-368
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Terminal Half-Life (t1/2) of ABBV-368
Time to Maximum Serum Concentration (Tmax) of ABBV-181 (Arm 3 Only)
Time Frame: Cycle 1 through Cycle 3 (each cycle is approximately 28 days)
Time to Maximum Serum Concentration (Tmax) of ABBV-181
Secondary Outcomes
- Duration of Response (DOR)(Up to approximately 2 years following the first dose)
- Objective Response Rate (ORR)(Up to approximately 2 years following the first dose)
- Time to Response (TTR)(Up to approximately 2 years following the first dose)
- Clinical Benefit Rate (CBR)(Up to approximately 2 years following the first dose)
- Progression Free Survival (PFS)(Up to approximately 2 years following the first dose)