Clinical trial NCT04777994: Study With ABBV-CLS-484 in Participants With Locally Advanced or Metastatic Tumors
Official title: A Phase 1 Study With ABBV-CLS-484 Alone and in Combination in Subjects With Locally Advanced or Metastatic Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor Cancer
Keywords: Cancer
Tumor
anti-PD-1
ABBV-CLS-484
clear cell renal cell carcinoma (ccRCC)
head and neck squamous cell carcinoma (HNSCC)
non-small cell lung cancer (NSCLC)
relapsed or refractory (R/R)
Microsatellite instability - high tumors (MSI-H)
Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Calico Life Sciences LLC
First posted: 2021-03-02
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The study will assess the safety, PK, PD, and preliminary efficacy of ABBVCLS-484 as monotherapy and in combination with a PD-1 targeting agent or with a or a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI).

The trial aims to establish a safe, tolerable, and efficacious dose of ABBVCLS-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 or with a VEGFR TKI 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 or with a VEGFR TKI agent in subjects with locally advanced or metastatic, HNSCC, NSCLC, MSI-H tumors refractory to PD-1/PD-L1, and advanced ccRCC.


Eligibility 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:

* Participants with histologically or cytologically proven metastatic or locally advanced tumors, 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 Monotherapy Dose Expansion only:

* Participants 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
* Participants no recent history of hemorrhage, including hemoptysis, hematemesis, or melena
* Participants with poorly controlled hypertension are excluded.

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 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.
* 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.

Primary outcomes:
measure: Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy)
timeFrame: Baseline Up to Approximately Day 42
measure: Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of Programmed Cell Death-1 (PD-1) Inhibitor (Combination therapy)
timeFrame: Baseline Up to Approximately Day 64
measure: Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFRTKI (Combination therapy) Maximum plasma/serum concentration of PD-1 inhibitor
timeFrame: Baseline Up to Approximately Day 64
measure: Dose Escalation: Time To Cmax (Tmax) Of ABBV-CLS-484 (Monotherapy)
timeFrame: Baseline Up to Approximately Day 42
measure: Dose Escalation: Time To Cmax (Tmax) Of PD-1 Inhibitor (Combination therapy)
timeFrame: Baseline Up to Approximately Day 64
measure: Dose Escalation Time to Cmax (Tmax) of VEGFR TKI (Combination therapy)
timeFrame: Baseline Up to Approximately Day 64
measure: Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of ABBV-CLS-484 (Monotherapy)
timeFrame: Baseline Up to Approximately Day 42
measure: Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of PD-1 Inhibitor (Combination therapy)
timeFrame: Baseline Up to Approximately Day 64
measure: Dose Escalation: Phase Elimination Rate Half-Life (t1/2) Of VEGFR TKI (Combination therapy)
timeFrame: Baseline Up to Approximately Day 64
measure: Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-484 (Monotherapy)
timeFrame: Baseline Up to Approximately Day 42
measure: Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor (Combination therapy)
timeFrame: Baseline Up to Approximately Day 64
measure: Dose Escalation: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI (Combination therapy)
timeFrame: Baseline Up to Approximately Day 64
measure: Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484
timeFrame: Baseline Up to Approximately Day 42
measure: Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a PD-1 Inhibitor (Combination therapy)
timeFrame: Baseline Up to Approximately Day 64
measure: Dose Escalation: Recommended Phase 2 Dose (RP2D) and/or Maximum Tolerated Dose of ABBV-CLS-484 and a VEGFR TKI (Combination therapy)
timeFrame: Baseline Up to Approximately Day 64
measure: Dose Expansion: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy)
timeFrame: Baseline Up to Approximately Day 42
measure: 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)
timeFrame: Baseline Up to Approximately Day 64
measure: 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)
timeFrame: Baseline Up to Approximately Day 64
Secondary outcomes:
measure: Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On (RECIST) v1.1 (Monotherapy)
timeFrame: Baseline through Study Completion (approximately 3 years)
measure: 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)
timeFrame: Baseline through Study Completion (approximately 3 years)
measure: 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)
timeFrame: Baseline through Study Completion (approximately 3 years)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center - Tucson /ID# 262698
state: Arizona
city: New Haven
country: United States
facility: Yale University School of Medicine /ID# 225707
state: Connecticut
city: Baltimore
country: United States
facility: Johns Hopkins Hospital /ID# 254056
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center /ID# 252009
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 249642
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 252010
state: Michigan
city: New York
country: United States
facility: NYU Laura and Isaac Perlmutter Cancer Center - 34th Street /ID# 257869
state: New York
city: Durham
country: United States
facility: Duke Cancer Center /ID# 251975
state: North Carolina
city: Huntersville
country: United States
facility: Carolina BioOncology Institute /ID# 225704
state: North Carolina
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine /ID# 250188
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Ctr /ID# 225706
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan Cancer Institute at Rhode Island Hospital /ID# 225705
state: Rhode Island
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center /ID# 251974
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center /ID# 252004
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology /ID# 225708
state: Texas
city: Marseille
country: France
facility: Institut Paoli-Calmettes /ID# 260956
state: Bouches-du-Rhone
city: Toulouse Cedex 9
country: France
facility: IUCT Oncopole /ID# 252673
state: Occitanie
city: Nice
country: France
facility: Centre Antoine-Lacassagne /ID# 252606
state: Provence-Alpes-Cote-d Azur
city: Suresnes CEDEX
country: France
facility: Hopital Foch /ID# 252607
city: Petah Tikva
country: Israel
facility: Rabin Medical Center /ID# 263631
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 226756
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center /ID# 252366
state: Yerushalayim
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 225884
state: Tokyo
city: Wakayama-shi
country: Japan
facility: Wakayama Medical University Hospital /ID# 252988
state: Wakayama
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 254635
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center /ID# 260664
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital /ID# 260665
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Català d'Oncologia (ICO) - L'Hospitalet /ID# 252524
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre /ID# 257374
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro /ID# 228034
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: