Clinical trial NCT05599984: Study to Evaluate Adverse Events, Change in Disease Activity, and How ABBV-706 Moves Through the Body When Intravenously (IV) Infused Alone or in Combination With IV Infused Budigalimab, Cisplatin, or Carboplatin in Adult Participants With Advanced Solid Tumors
Official title: A Phase 1 First-in-Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV-706 as Monotherapy and in Combination With Budigalimab (ABBV-181), Carboplatin, or Cisplatin in Adult Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Advanced Solid Tumors
Small Cell Lung Cancer
Central Nervous System Tumors
ABBV-706
ABBV-181
Budigalimab
Platinum Chemotherapy Combination
Carboplatin
Cisplatin
Neuroendocrine Carcinomas
Cancer
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2022-10-31
Enrollment: 350
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: Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess safety, tolerability, pharmacokinetics and preliminary efficacy of ABBV-706 as a monotherapy and in combination with budigalimab, carboplatin, or cisplatin.

ABBV-706 is an investigational drug being developed for the treatment of small cell lung cancer (SCLC), high-grade central nervous system (CNS) tumors and high-grade neuroendocrine carcinomas (NECs). There are multiple treatment arms in this study. Participants will either receive ABBV-706 as a single agent or in combination with budigalimab (another investigational drug), carboplatin or cisplatin at different doses. Approximately 350 adult participants will be enrolled in the study across sites worldwide.

In part 1 (dose escalation), ABBV-706 will be intravenously infused in escalating doses as a monotherapy until the maximum tolerated dose (MTD) is determined in participants with SCLC, high-grade CNS tumors, and high-grade NECs. In part 2, multiple doses will be selected from Part 1 and SCLC participants will be assigned to one of these doses in a randomized fashion to determine the recommended Phase 2 dose. In Part 3a, participants with SCLC or NECs will receive ABBV-706 in combination with budigalimab intravenously every 3 weeks. In Part 3b participants with SCLC or NECs will receive ABBV-706 in combination with either carboplatin or cisplatin intravenously. In Part 4a, participants with CNS tumors will receive ABBV-706 intravenously at a dose determined from Part 1. In Part 4b, participants with NECs will receive ABBV-706 intravenously at a dose selected from Part 1. The estimated duration of the study is up to 3 years.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and scans.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* The laboratory values criteria must be met within 7 days prior to the first dose of study drug as per the protocol.
* QT interval corrected for heart rate (QTc) \<= 450 msec (males) or \<= 470 msec (females) using Fridericia's correction, and an ejection fraction of \>= 50% as measured by echocardiogram or multigated acquisition (MUGA) scan at Screening.
* Part 1 only: Advanced recurrent or refractory solid tumors with potential SEZ6 expression including small cell lung cancer (SCLC), high-grade central nervous system (CNS) tumors (glioblastoma \[GBM\], IDH-wildtype Grade 4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma, IDH-mutant Grade 3 or Grade 4), neuroendocrine prostate cancer (NEPC), high-grade poorly differentiated gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC)s, large cell neuroendocrine carcinoma (LCNEC)s, SCLC transformed from epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), atypical lung carcinoids, and other high-grade poorly differentiated NECs, who have progressed on or after standard of care (SoC) therapy and with no curative therapy available. For SCLC, participants must have histologically or cytologically confirmed SCLC that is relapsed or refractory following at least 1 prior platinum-containing chemotherapy.
* Part 2 only: Histologically or cytologically confirmed SCLC that is relapsed or refractory (R/R) following at least 1 prior platinum-containing chemotherapy and with no curative therapy available. For the purposes of this study, a line of therapy is defined as \>= 1 complete cycle of either a single agent or combination of drugs, including any planned sequential therapy of various regimens.
* Part 3a only: Participants with R/R SCLC following at least 1 prior platinum-containing chemotherapy or R/R poorly differentiated NECs, e.g., NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant Non-small cell lung cancer (NSCLC), atypical lung carcinoids, other high-grade poorly differentiated NECs.
* Part 3b only: Participants with R/R SCLC who have only progressed following a frontline regimen containing a platinum-based chemotherapy or R/R NECs, e.g., NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant NSCLC, atypical lung carcinoids, other NECs.
* Part 4a only: Participants with R/R high-grade CNS tumors (GBM, IDH-wildtype Grade 4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma, IDH-mutant Grade 3 or Grade 4) who have progressed on SoC therapy and with no curative therapy options available.
* Part 4b only: Participants with R/R neuroendocrine tumors, including NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant NSCLC, atypical lung carcinoids, and other high-grade poorly differentiated NECs, who have progressed on SoC therapy and with no curative therapy options available.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for participants with extracranial solid tumors or Response Assessment for Neuro-Oncology (RANO)for participants with primary high-grade CNS tumors (GBM, IDH-wildtype Grade 4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma, IDH-mutant Grade 3 or Grade 4).
* Primary CNS tumors within 12 weeks from radiation therapy should have unequivocal progression as documented by either tumor recurrence predominantly outside of radiation field on magnetic resonance imaging (MRI) or confirmed on tumor biopsy.
* Participants with brain metastases from an extracranial solid tumor are eligible if the brain metastases as outlined in the protocol.
* Fresh or archival tumor tissue available for submission, for retrospective SEZ6 expression analysis as outlined in the protocol.

Exclusion Criteria:

* History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, nor any evidence of active ILD or pneumonitis.
* History of idiopathic pulmonary fibrosis or organizing pneumonia.
* Prior treatment with an antibody drug conjugate that consists of a Top1 inhibitor payload.
* Part 2 only: Prior treatment with a SEZ6-targeted antibody drug conjugate.

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AE)
timeFrame: Up to Approximately 2 Years
measure: Maximum Observed Serum/Plasma Concentration (Cmax) of ABBV-706
timeFrame: Up to Approximately 2 Years
measure: Time to Cmax (Tmax) of ABBV-706
timeFrame: Up to Approximately 2 Years
measure: Terminal Phase Elimination Half-Life (t1/2) of ABBV-706
timeFrame: Up to Approximately 2 Years
measure: Area Under the Serum/Plasma Concentration-Time Curve (AUC) of ABBV-706
timeFrame: Up to Approximately 2 Years
measure: Antidrug Antibodies (ADAs)
timeFrame: Up to Approximately 2 Years
measure: Neutralizing Antibodies (nAbs)
timeFrame: Up to Approximately 2 Years
measure: Percentage of Participants with Objective Response, for Participants with Extracranial Solid Tumors
timeFrame: Up to Approximately 2 Years
measure: Recommended Phase 2 Dose (RP2D) of ABBV-706
timeFrame: Up to Approximately 2 Years
measure: Percentage of Participants with Objective Response for Participants with Central Nervous System (CNS) Tumors
timeFrame: Up to Approximately 2 Years
measure: Duration of response (DOR) for Participants with Confirmed CR/PR
timeFrame: Up to Approximately 2 Years
measure: Percentage of Participants with Clinical Benefit
timeFrame: Up to Approximately 2 Years
measure: Progression-Free Survival (PFS)
timeFrame: Up to Approximately 2 Years
measure: Overall survival (OS)
timeFrame: Up to Approximately 2 Years
Secondary outcomes:
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Ctr /ID# 260129
state: Arizona
city: Duarte
country: United States
facility: City Of Hope Comprehensive Cancer Center /ID# 271295
state: California
city: Irvine
country: United States
facility: City of Hope Orange County Lennar Foundation Cancer Center /ID# 259884
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital /ID# 246647
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Hospital /ID# 255352
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago /ID# 256334
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc /ID# 260130
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics /ID# 246638
state: Iowa
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer In /ID# 261799
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital /ID# 246648
state: Michigan
city: Grand Rapids
country: United States
facility: START Midwest /ID# 251257
state: Michigan
city: Kansas City
country: United States
facility: St. Luke's Hosp. of Kansas City /ID# 259958
state: Missouri
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 246286
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center-Koch Center /ID# 246303
state: New York
city: Durham
country: United States
facility: Duke Cancer Center /ID# 246285
state: North Carolina
city: Cleveland
country: United States
facility: UH Cleveland Medical Center /ID# 246641
state: Ohio
city: Oklahoma City
country: United States
facility: Univ Oklahoma HSC /ID# 250884
state: Oklahoma
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC /ID# 246283
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center /ID# 246287
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics /ID# 248946
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah /ID# 246640
state: Utah
city: Tacoma
country: United States
facility: Northwest Medical Specialties - Tacoma /ID# 262801
state: Washington
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse /ID# 259087
state: New South Wales
city: Darlinghurst
country: Australia
facility: The Kinghorn Cancer Centre /ID# 260874
state: New South Wales
city: Heidelberg
country: Australia
facility: Austin Health and Ludwig Institute for Cancer Research /ID# 255174
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Ctr /ID# 259197
state: Victoria
city: Beijing
country: China
facility: Cancer Hospital - Chinese Academy Of Medical Sciences /ID# 270044
state: Beijing
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 270038
state: Hubei
city: Shenyang
country: China
facility: The first hospital of China medical University /ID# 270041
state: Liaoning
city: Shanghai
country: China
facility: Shanghai Chest Hospital /ID# 270036
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital /ID# 268615
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital /Id# 270039
state: Shanghai
city: Bordeaux
country: France
facility: Institut Bergonie /ID# 258655
state: Gironde
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy /ID# 260334
state: Val-de-Marne
city: Montpellier
country: France
facility: Institut Régional du Cancer Montpellier /ID# 265086
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Campus Innenstadt /ID# 259412
state: Bayern
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin /ID# 259413
city: Dresden
country: Germany
facility: Technische Universitat Dresden /ID# 259414
city: Haifa
country: Israel
facility: Rambam Health Care Campus /ID# 255059
state: H_efa
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 254915
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Hebrew University /ID# 255147
city: Milan
country: Italy
facility: Istituto Europeo Di Oncologia /ID# 256804
state: Milano
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori - Ospedale San Gerardo /ID# 258228
state: Monza E Brianza
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 259417
state: Chiba
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center /ID# 261279
state: Ehime
city: Sapporo-shi
country: Japan
facility: Hokkaido Cancer Center /ID# 261278
state: Hokkaido
city: Kyoto-shi
country: Japan
facility: Kyoto University Hospital /ID# 259419
state: Kyoto
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center /ID# 261277
state: Shizuoka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 259418
state: Tokyo
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital Of JFCR /ID# 260132
state: Tokyo
city: Wakayama-shi
country: Japan
facility: Wakayama Medical University Hospital /ID# 260131
state: Wakayama
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center /ID# 248938
state: Gyeonggido
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Center /ID# 248939
state: Gyeonggido
city: Hwasun-gun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital /ID# 248943
state: Jeonranamdo
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 248940
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center /ID# 248936
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital /ID# 248937
city: Barcelona
country: Spain
facility: Hospital HM Nou Delfos /ID# 264851
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 258659
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau /ID# 257294
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal /ID# 257291
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz /ID# 257295
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre /ID# 258658
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro /ID# 258657
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio /ID# 256940
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia /ID# 257290
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: