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

• ClinicalTrials.gov Identifier: NCT04777994
• Recruitment Status: Recruiting
• First Posted: March 2, 2021
• Last Update Posted: April 6, 2021
• Sponsor: Calico Life Sciences LLC
• Collaborator: AbbVie
• Information provided by (Responsible Party): Calico Life Sciences LLC

Study Description

Brief Summary:

The study will assess the safety, PK, PD, and preliminary efficacy of ABBV-CLS-484 as monotherapy and in combination with a PD-1 targeting agent. The trial aims to establish a safe, tolerable, and efficacious dose of ABBV-CLS-484 as monotherapy and in combination. The study will be conducted in three parts. Part 1 Monotherapy Dose Escalation, Part 2 Combination Dose Escalation and Part 3 Dose Expansion (Monotherapy and Combination therapy).

Part 1, ABBV-CLS-484 will be administered alone in escalating dose levels to eligible subjects who have advanced solid tumors.

Part 2, ABBV-CLS-484 will be administered at escalating dose levels in combination with a PD-1 targeting agent to eligible subjects who have advanced solid tumors.

Part 3, ABBV-CLS-484 will be administered alone as a monotherapy 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). ABBV-CLS-484 will also be administered at the determined recommended dose in combination with a PD-1 targeting agent in subjects with locally advanced or metastatic, relapsed or refractory gastric or GEJ adenocarcinoma.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor Cancer	Drug: ABBV-CLS-484; Drug: Programmed Cell Death-1 (PD-1) Inhibitor	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: March 9, 2021
• Estimated Primary Completion Date: October 30, 2023
• Estimated Study Completion Date: February 22, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Monotherapy Dose Escalation; ABBV-CLS-484 will be administered as a monotherapy in subjects with solid tumors	Drug: ABBV-CLS-484; Oral Capsule
Experimental: Combination Dose Escalation; ABBV-CLS-484 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors	Drug: ABBV-CLS-484; Oral Capsule; Drug: Programmed Cell Death-1 (PD-1) Inhibitor; Intravenous (IV) infusion
Experimental: 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)	Drug: ABBV-CLS-484; Oral Capsule
Experimental: Combination Expansion; 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, relapsed or refractory gastric or GEJ adenocarcinoma	Drug: ABBV-CLS-484; Oral Capsule; Drug: Programmed Cell Death-1 (PD-1) Inhibitor; Intravenous (IV) infusion

Outcome Measures

Primary Outcome Measures :

1. Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
   Maximum plasma/serum concentration of ABBV-CLS-484
2. Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of Programmed Cell Death-1 (PD-1) Inhibitor (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
   Maximum plasma/serum concentration of PD-1 inhibitor
3. Dose Escalation: Time To Cmax (Tmax) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
   The amount of time taken to reach Cmax
4. Dose Escalation: Time To Cmax (Tmax) Of PD-1 Inhibitor (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
   The amount of time taken to reach Cmax
5. Dose Escalation: Terminal Phase Elimination Rate Constant (β) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
   Terminal phase elimination rate constant (β or Beta)
6. Dose Escalation: Phase Elimination Rate Constant (β) Of PD-1 Inhibitor (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
   Terminal phase elimination rate constant (β or Beta)
7. Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
   Terminal phase elimination half-life (t1/2)
8. Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
   Terminal phase elimination half-life (t1/2)
9. Dose Escalation: Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
   AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
10. Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
    AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
11. Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 (Monotherapy) [ Time Frame: Baseline Up to Approximately Day 42 ]
    The MTD and/or RP2D of ABBV-CLS-484 will be determined during the monotherapy dose escalation phase of the study
12. Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a PD-1 Inhibitor (Combination therapy) [ Time Frame: Baseline Up to Approximately Day 64 ]
    The MTD and/or RP2D of ABBV-CLS-484 and PD-1 inhibitor will be determined during the combination therapy dose escalation phase of the study
13. Dose Expansion: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy) [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
    ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
14. 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) [ Time Frame: Baseline Up to Approximately Day 64 ]
    ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment

Secondary Outcome Measures :

1. Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy) [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
   ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
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) [ Time Frame: Baseline through Study Completion (approximately 3 years) ]
   ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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 1 prior line containing PD-1/PD-L1 targeted therapy with a best response of CR/PR/stable disease by RECIST v1.1 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 Combination Dose Expansion only:

• Subjects with gastric or GEJ adenocarcinoma whose tumors express PD-L1 (CPS ≥1)
• Must not have received a PD-1/PD-L1 targeting agent, or other immune-oncology agents as part of a prior line of therapy;
• Must have received, and progressed on, at least 2 prior lines of chemotherapy in the locally advanced or metastatic setting; •. If tumor is HER2/neu positive, subject must have received prior treatment with an approved HER2 targeting therapy.

Exclusion Criteria:

• 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:

  • No 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.

Contacts and Locations

Contacts

Contact: ABBVIE CALL CENTER; 847.283.8955; abbvieclinicaltrials@abbvie.com

Locations

United States, North Carolina

Carolina BioOncology Institute; Recruiting

Huntersville, North Carolina, United States, 28078

United States, Texas

Next Oncology; Recruiting

San Antonio, Texas, United States, 78229

Japan

National Cancer Center Hospital; Recruiting

Chuo-ku, Tokyo, Japan, 104-0045

Sponsors and Collaborators

Calico Life Sciences LLC

AbbVie

More Information

• Responsible Party: Calico Life Sciences LLC
• ClinicalTrials.gov Identifier: NCT04777994
• Other Study ID Numbers: M20-431
• First Posted: March 2, 2021
• Last Update Posted: April 6, 2021
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Calico Life Sciences LLC:

Cancer; Tumor; anti-PD-1; ABBV-CLS-484; clear cell renal cell carcinoma (ccRCC); gastroesophageal junction (GEJ); head and neck squamous cell carcinoma (HNSCC); non-small cell lung cancer (NSCLC); relapsed or refractory (R/R); gastric; GEJ adenocarcinoma

Additional relevant MeSH terms:

Neoplasm Metastasis; Neoplasms; Neoplastic Processes; Pathologic Processes