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[M20-431] A Phase 1, Multi-center, Open Label First-in-Human Study With ABBV-CLS-484 Alone and in Combination in Subjects With Locally Advanced or Metastatic Tumors

[M20-431] A Phase 1 Study With ABBV-CLS-484 in Subjects With Locally Advanced or Metastatic Tumors

Yamagishi Chika

AbbVie G.K.

3-1-21 Shibaura, Minato-ku, Tokyo

AbbVie_JPN_info_clingov@abbvie.com

Contact for Patients and HCP

AbbVie G.K.

3-1-21 Shibaura, Minato-ku, Tokyo

+81-120-587-874

AbbVie_JPN_info_clingov@abbvie.com

Recruiting

April. 08, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

- Must weigh at least 35 kilograms (kg).
- An Eastern Cooperative Oncology Group (ECOG) performance status =< 2.
- Life expectancy of =>12 weeks.
- Laboratory values meeting protocol criteria.
- QT interval corrected for heart rate < 470 msec (using Fridericia's correction), and no clinically significant electrocardiographic findings.
- Measurable disease defined by RECIST 1.1 criteria.

For Monotherapy and Combination Dose Escalation:
- Subjects with histologically or cytologically proven metastatic or locally advanced tumors, for which no effective standard therapy exists, or where standard therapy has failed. Subjects must have received at least 1 prior systemic anticancer therapy for the indication being considered.

For Monotherapy Dose Expansion only:
- Subjects must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy with a best response by RECIST v1.1 of CR/PR/stable (any duration) or stable disease (for greater than 6 months); AND
- Must have been previously treated with 1 or more prior lines of therapy in the locally advanced or metastatic setting with the following tumor types:
- Relapsed/refractory HNSCC
- Relapsed/refractory NSCLC
- Advanced ccRCC

For PD-1 Targeting Agent Combination Dose Expansion only:
- For the following tumor types, subject must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy with response by RECIST v1.1 of CR/PR (any duration) or stable disease (for greater than 6 months):
- Relapsed HNSCC
- Relapsed NSCLC
- Relapsed Advanced ccRCC
- For the following tumor types, subject must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy and have had disease progression with PD-1/PD-L1 targeted therapy:
- Locally Advanced or metastatic MSI-H tumors

For VEGFR TKI Combination Dose Expansion only:
- Relapsed advance ccRCC with no more than 1 prior VEGFR TKI
- Subjects no recent history of hemorrhage, including hemoptysis, hematemesis, or melena
- Subjects with poorly controlled hypertension are excluded

- Untreated brain or meningeal metastases (i.e., subjects with history of metastases are eligible provided they do not require ongoing steroid treatment and have shown clinical and radiographic stability for at least 28 days after definitive therapy)
- Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except alopecia.
- Unresolved Grade 2 or higher peripheral neuropathy.
- History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
- Recent history (within 6 months) of congestive heart failure (defined as New York Heart Association, Class 2 or higher), ischemic cardiovascular event, pericarditis, or clinically significant pericardial effusion or arrythmia.
- Recent history (within 6 months) of Childs-Pugh B or C classification of liver disease.
- History of clinically significant medical and/or psychiatric conditions or any other reason that, in the opinion of the investigator, would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug.
- History of uncontrolled, clinically significant endocrinopathy.
- Known gastrointestinal disorders making absorption of oral medications problematic; subject must be able to swallow capsules.
- If treated with a PD-1/aPD-L1 targeting or other immune-oncology agents in the past, excluded if had prior pneumonitis, prior Grade 3 or higher immune mediated toxicity, hypersensitivity to administered drug or drug related toxicity requiring discontinuation.
- Active autoimmune disease requiring systemic treatment in past 2-years (exceptions for endocrinopathies, vitiligo or atopic conditions).
- History of solid organ transplant or allogeneic stem cell transplant.
- History of other malignancy, with the following exceptions:
- Known active disease present for >= 3 years before first dose of study treatment and felt to be at low recurrence by investigator.
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- Adequately treated carcinoma in situ without evidence of disease.

- History of interstitial lung disease or pneumonitis.
- Major surgery <= 28 days prior to first dose of study drug
- Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per local testing practices.

Both

Advanced Solid Tumor

Monotherapy Dose Escalation
ABBV-CLS-484 will be administered as a monotherapy in subjects with solid tumors

Combination Dose Escalation with PD-1 Inhibitor
ABBV-CLS-484 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors

Monotherapy Expansion
ABBV-CLS-484 will be administered at the determined recommended dose in subjects with locally advanced or metastatic, relapsed or refractory head and neck squamous cell carcinoma (HNSCC), relapsed or refractory non-small cell lung cancer (NSCLC), and advanced clear cell renal cell carcinoma (ccRCC)

Combination Expansion with PD-1 Inhibitor
ABBV-CLS-484 will be administered at the determined recommended dose in combination with Programmed Cell Death-1 Inhibitor in subjects with locally advanced or metastatic HNSCC, NSCLC, MSI-H tumors refractory to PD-1/PD-L1, and advanced ccRCC.

Combination Dose Escalation with VEGFR TKI
ABBV-CLS-484 will be administered in combination with a Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI) in subjects with solid tumors

Combination Expansion with VEGFR TKI
ABBV-CLS-484 will be administered at the determined recommended dose in combination with VEGFR TKI in subjects with locally advanced or metastatic, HNSCC, NSCLC, MSI-H tumors refractory to PD-1/PD-L1, and advanced ccRCC.

1. Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy)
2. Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of Programmed Cell Death-1 (PD-1) Inhibitor (Combination therapy)
3. Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFR TKI (Combination therapy)
4. Dose Escalation: Time To Cmax (Tmax) Of ABBV-CLS-484 (Monotherapy)
5. Dose Escalation: Time To Cmax (Tmax) Of PD-1 Inhibitor (Combination therapy)
6. Dose Escalation Time to Cmax (Tmax) of VEGFR TKI (Combination therapy)
7. Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484 (Monotherapy)
8. Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor (Combination therapy)
9. Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of VEGFR TKI (Combination therapy)
10. Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-484 (Monotherapy)
11. Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor (Combination therapy)
12. Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI (Combination therapy)
13. Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484
14. Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a PD-1 Inhibitor (Combination therapy)
15. Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a VEGFR TKI (Combination therapy)
16. Dose Expansion: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy)
17. Dose Expansion: Objective Response Rate (ORR) Of ABBV-CLS-484 And PD-1 Targeting Agent Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Combination therapy)
18. Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 And VEGFR TKI Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Combination therapy)

1. Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy)
2. Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 And PD-1 Targeting Agent Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Combination therapy)
3. Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 And VEGFR TKI Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Combination therapy)

+81-3-3542-2511

Mar. 26, 2021

Yes

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. Supporting Information: Study Protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR), Analytic Code Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link. URL: https://www.abbvie.com/ourscience/clinicaltrials/clinicaltrialsdataandinformationsharing.html

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