[M20-124] First In Human Study With ABBV-CLS-579 When Given Alone and In Combination In Participants With Locally Advanced Or Metastatic Tumors

JRCT ID: jRCT2080225298

Registered date:31/07/2020

Basic Information

• Recruitment status: recruiting
• Health condition(s) or Problem(s) studied: Advanced Solid Tumors
• Date of first enrollment: 25/08/2020
• Target sample size: 263
• Countries of recruitment: Japan,United States,France,Israel,Korea,Taiwan
• Study type: Interventional

Intervention(s)

investigational material(s)
Generic name etc :
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material :

control material(s)
Generic name etc :
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material :
Generic name etc :
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material :

Outcome(s)

Primary Outcome

safety
exploratory
pharmacokinetics
1. Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-579
2. Maximum Observed Plasma/Serum Concentration (Cmax) Of Metabolite M4
3. Maximum Observed Plasma/Serum Concentration (Cmax) Of PD-1 Inhibitor
4. Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFR TKI
5. Time To Cmax (Tmax) Of ABBV-CLS-579
6. Time To Cmax (Tmax) Of Metabolite M4
7. Time To Cmax (Tmax) Of PD-1 Inhibitor
8. Time To Cmax (Tmax) Of VEGFR TKI
9. Terminal Phase Elimination Rate Constant (Beta) Of ABBV-CLS-579
10. Terminal Phase Elimination Rate Constant (Beta) Of Metabolite M4
11. Terminal Phase Elimination Rate Constant (Beta) Of PD-1 Inhibitor
12. Terminal Phase Elimination Rate Constant (Beta) Of VEGFR TKI
13. Terminal Phase Elimination Half-Life (t1/2) Of ABBV-CLS-579
14. Terminal Phase Elimination Half-Life (t1/2) Of Metabolite M4
15. Terminal Phase Elimination Half-Life (t1/2) Of PD-1 Inhibitor
16. Terminal Phase Elimination Half-Life (t1/2) Of VEGFR TKI
17. Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-579
18. Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of Metabolite M4
19. Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor
20. Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI
21. Recommended Expansion Dose and/or Maximum Tolerated Dose of ABBV-CLS-579
22. Recommended Expansion Dose and/or Maximum Tolerated Dose of ABBV-CLS-579 and a PD-1 Inhibitor
23. Objective Response Rate (ORR) Of ABBV-CLS-579 And PD-1 Targeting Agent Base On Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, of ABBV-CLS-579 in locally or metastatic HNSCC, NSCLC, MSI-H tumors, and advanced ccRCC
24. Objective Response Rate (ORR) on RECIST v1.1, of ABBV-CLS-579 administered in combination with VEGFR TKI in advanced ccRCC

Secondary Outcome

efficacy
exploratory
other
1. Objective Response Rate (ORR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
2. Objective Response Rate (ORR) Of ABBV-CLS-579 Monotherapy Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
3. Best Overall Response (BOR) Of ABBV-CLS-579 Monotherapy Based On RECIST v1.1
4. Best Overall Response (BOR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On RECIST v1.1
5. Change from Baseline QTc

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Must weigh at least 35 kilograms (kg).
- For Monotherapy and Combination Dose Escalation:
- Histologically or cytologically proven metastatic or locally advanced tumors (with measurable disease defined by Response Evaluation Criteria In Solid Tumors [RECIST] v1.1), for which no effective standard therapy exists, or where standard therapy has failed. Participants must have received at least 1 prior systemic anticancer therapy for the indication being considered.
- For Combination Dose Expansion:
- For the following tumor types, the subject must have received at least 1 prior line containing PD-1/PD-L1 target therapy.
- Indication with outcome of Prior PD-1/PD-L1 Targeted Therapy and other disease characteristics:
- NSCLC
- Relapsed: Tumors express PD-L1 (TPS >= 1%) as determined by the FDA-approved Agilent PD-L1 IHC 22C3 pharmDx kit
- Refractory: Tumors express PD-L1 (TPS >= 1%) as determined by the FDA-approved Agilent PD-L1 IHC 22C3 pharmDx kit
- ccRCC
- Relapsed or Refractory: Advanced disease (locally advanced or metastatic)
- MSI-H tumors
- Refractory: Locally advanced or metastatic MSI-H tumors whose tumors are determined to have a MSI-H status by PCR or NGS tests, or dMMR by IHC tests.
- HNSCC
- Relapsed or Refractory: Tumors express PD-L1 (CPS >= 1] as determined by the FDA approved PD-L1 Agilent IHC 22C3 pharmDx kit
- For Combination Dose Expansion:
- Locally advanced or metastatic, advanced ccRCC who have relapsed after at least 1 prior VEGFR TKI therapy
- Received at least 1 prior line containing PD 1/PD L1 targeted therapy with a best response by RECIST v1.1 of CR/PR (any duration) or stable disease (for greater than 6 months)
- Received at least 1 prior line containing PD-1/PD-L1 targeted therapy and have had disease progression (in the absence of best response of CR/PR/stable disease by RECIST v1.1) with PD 1/PD L1 targeted therapy
- An Eastern Cooperative Oncology Group (ECOG) performance status <= 2.
- Life expectancy of >= 12 weeks.
- Laboratory values meeting protocol criteria.
- If the subject is on anticoagulant therapy, INR must be within therapeutic goal.
- QT interval corrected for heart rate < 450 msec (using Fridericia's correction), and no clinically significant electrocardiographic findings.

Exclude criteria

- Untreated brain or meningeal metastases (participants with history of metastases are eligible provide 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.
- 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, cardiac arrythmia or peripheral artery disease.
- 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 participation in this study or would make the participant an unsuitable candidate to receive study drug.
- History of uncontrolled, clinically significant endocrinopathy.
- Known gastrointestinal disorders making absorption of oral medications problematic. Inability to swallow capsules.
- If treated with anti-programmed cell death protein-1 (aPD-1)/antiprogrammed cell death protein-ligand 1(aPD-L1) targeting or other immunostimulatory 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 interstitial lung disease or pneumonitis.
- Major surgery <= 28 days prior to first dose of study drug.
- Poorly controlled hypertension
- History of hemorrhage, including hemoptysis, hematemesis, or melena
- History of other malignancy, with the following exceptions:
- No known active disease present for within 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
- Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per local testing practices.

Related Information

• Primary Sponsor: Calico Life Sciences LLC
• Secondary Sponsor: AbbVie GK (In-Country Clinical Caretaker)
• Secondary ID(s): NCT04417465