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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05599984
• Other study ID #: M23-385
• Status: Recruiting
• Phase: Phase 1
• Start date: December 5, 2022
• Est. completion date: May 17, 2027

Study information

• Verified date: June 2024
• Source: AbbVie
• Contact: ABBVIE CALL CENTER
• Phone: 844-663-3742
• Email: abbvieclinicaltrials[@]abbvie.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: May 17, 2027
• Est. primary completion date: October 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• ABBV-706
Intravenous (IV) Infusion
• Cisplatin
Intravenous infusion
• Budigalimab
IV Infusion
• Carboplatin
Intravenous infusion

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse /ID# 259087	Camperdown	New South Wales
Australia	The Kinghorn Cancer Centre /ID# 260874	Darlinghurst	New South Wales
Australia	Austin Health and Ludwig Institute for Cancer Research /ID# 255174	Heidelberg	Victoria
Australia	Peter MacCallum Cancer Ctr /ID# 259197	Melbourne	Victoria
Germany	Technische Universitat Dresden /ID# 259414	Dresden
Israel	Rambam Health Care Campus /ID# 255059	Haifa	H_efa
Israel	Hadassah Medical Center-Hebrew University /ID# 255147	Jerusalem
Israel	The Chaim Sheba Medical Center /ID# 254915	Ramat Gan	Tel-Aviv
Japan	National Cancer Center Hospital /ID# 259418	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East /ID# 259417	Kashiwa-shi	Chiba
Japan	The Cancer Institute Hospital Of JFCR /ID# 260132	Koto	Tokyo
Japan	Kyoto University Hospital /ID# 259419	Kyoto-shi	Kyoto
Japan	National Hospital Organization Shikoku Cancer Center /ID# 261279	Matsuyama-shi	Ehime
Japan	Hokkaido Cancer Center /ID# 261278	Sapporo-shi	Hokkaido
Japan	Shizuoka Cancer Center /ID# 261277	Sunto-gun	Shizuoka
Japan	Wakayama Medical University Hospital /ID# 260131	Wakayama-shi	Wakayama
Korea, Republic of	National Cancer Center /ID# 248938	Goyang-si	Gyeonggido
Korea, Republic of	Chonnam National University Hwasun Hospital /ID# 248943	Hwasun-gun	Jeonranamdo
Korea, Republic of	CHA Bundang Medical Center /ID# 248939	Seongnam	Gyeonggido
Korea, Republic of	Samsung Medical Center /ID# 248936	Seoul
Korea, Republic of	Seoul National University Hospital /ID# 248940	Seoul
Korea, Republic of	Yonsei University Health System Severance Hospital /ID# 248937	Seoul	Seoul Teugbyeolsi
Spain	Hospital Universitario Vall d'Hebron /ID# 258659	Barcelona
Spain	Hospital Universitario 12 de Octubre /ID# 258658	Madrid
Spain	Hospital Universitario HM Sanchinarro /ID# 258657	Madrid
Spain	Hospital Universitario Ramon y Cajal /ID# 257291	Madrid
Spain	Hospital Clinico Universitario de Valencia /ID# 257290	Valencia
United States	UH Cleveland Medical Center /ID# 246641	Cleveland	Ohio
United States	Barbara Ann Karmanos Cancer In /ID# 261799	Detroit	Michigan
United States	Henry Ford Hospital /ID# 246648	Detroit	Michigan
United States	City of Hope /ID# 259884	Duarte	California
United States	Duke Cancer Center /ID# 246285	Durham	North Carolina
United States	Fort Wayne Medical Oncology and Hematology, Inc /ID# 260130	Fort Wayne	Indiana
United States	Banner MD Anderson Cancer Ctr /ID# 260129	Gilbert	Arizona
United States	START Midwest /ID# 251257	Grand Rapids	Michigan
United States	University of Texas MD Anderson Cancer Center /ID# 246287	Houston	Texas
United States	University of Iowa Hospitals and Clinics /ID# 246638	Iowa City	Iowa
United States	St. Luke's Hosp. of Kansas City /ID# 259958	Kansas City	Missouri
United States	Tennessee Oncology, PLLC /ID# 246283	Nashville	Tennessee
United States	Yale School of Medicine /ID# 246647	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center-Koch Center /ID# 246303	New York	New York
United States	Univ Oklahoma HSC /ID# 250884	Oklahoma City	Oklahoma
United States	Washington University-School of Medicine /ID# 246286	Saint Louis	Missouri
United States	University of Utah /ID# 246640	Salt Lake City	Utah
United States	South Texas Accelerated Research Therapeutics /ID# 248946	San Antonio	Texas
United States	Northwest Medical Specialties - Tacoma /ID# 262801	Tacoma	Washington
United States	Georgetown University Hospital /ID# 255352	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Israel,  Japan,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events (AE)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.	Up to Approximately 2 Years
Primary	Maximum Observed Serum/Plasma Concentration (Cmax) of ABBV-706	Maximum observed serum/plasma concentration of ABBV-706.	Up to Approximately 2 Years
Primary	Time to Cmax (Tmax) of ABBV-706	Time to Cmax of ABBV-706.	Up to Approximately 2 Years
Primary	Terminal Phase Elimination Half-Life (t1/2) of ABBV-706	Terminal phase elimination half-life (t1/2) of ABBV-706.	Up to Approximately 2 Years
Primary	Area Under the Serum/Plasma Concentration-Time Curve (AUC) of ABBV-706	Area under the serum/plasma concentration-time curve of ABBV-706.	Up to Approximately 2 Years
Primary	Antidrug Antibodies (ADAs)	Incidence and concentration of anti-drug antibodies.	Up to Approximately 2 Years
Primary	Neutralizing Antibodies (nAbs)	Incidence and concentration of neutralizing antibodies.	Up to Approximately 2 Years
Primary	Percentage of Participants with Objective Response, for Participants with Extracranial Solid Tumors	Objective response is defined as participants achieving a confirmed best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 for for extracranial solid tumors per investigator assessment.	Up to Approximately 2 Years
Primary	Recommended Phase 2 Dose (RP2D) of ABBV-706	The RP2D will be determined using all available information, including, but not limited to, AEs, dose-limiting toxicities, pharmacokinetic parameters, clinical laboratory tests, and efficacy measures.	Up to Approximately 2 Years
Primary	Percentage of Participants with Objective Response for Participants with Central Nervous System (CNS) Tumors	Objective response is as participants achieving a confirmed best overall response of CR and PR according to Response Assessment for Neuro-Oncology (RANO), version 1.1 for CNS tumors per investigator assessment.	Up to Approximately 2 Years
Primary	Duration of response (DOR) for Participants with Confirmed CR/PR	For participants achieving a confirmed CR/PR, DOR is defined as the time from the initial response of CR/PR to disease progression or death of any cause, whichever occurs earlier.	Up to Approximately 2 Years
Primary	Percentage of Participants with Clinical Benefit	Clinical benefit is defined as a participant achieving CR/PR, or Stable Disease (SD).	Up to Approximately 2 Years
Primary	Progression-Free Survival (PFS)	PFS is defined as time from first study treatment to a documented disease progression, as determined by the investigator, or death due to any cause, whichever occurs earlier.	Up to Approximately 2 Years
Primary	Overall survival (OS)	OS is defined as time from first study treatment to death due to any cause.	Up to Approximately 2 Years

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