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
- Conditions
- Advanced Solid Tumors
- Interventions
- Registration Number
- NCT05599984
- Lead Sponsor
- AbbVie
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 350
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 3a: ABBV-706 + Budigalimab ABBV-706 Participants will receive ABBV-706 in combination with budigalimab, as part of an approximately 1 year treatment period. Part 2: ABBV-706 Monotherapy Dose Optimization and Expansion ABBV-706 Participants with small cell lung cancer will receive varying doses of ABBV-706 in a randomized manner until the recommended phase 2 dose (RP2D) is achieved, as part of an approximately 1 year treatment period.. Part 3a: ABBV-706 + Budigalimab Budigalimab Participants will receive ABBV-706 in combination with budigalimab, as part of an approximately 1 year treatment period. Part 3b: ABBV-706 + Platinum Chemotherapy ABBV-706 Participants will receive ABBV-706 in combination with carboplatin or cisplatin, as part of an approximately 1 year treatment period. Part 1: ABBV-706 Monotherapy Dose Escalation ABBV-706 Participants will receive escalating doses of ABBV-706 until doses for optimization are determined, as part of an approximately 1 year treatment period. Part 4a: ABBV-706 Monotherapy Dose Expansion CNS Tumors ABBV-706 Participants with relapsed/refractory (R/R) central nervous system (CNS) tumors will receive ABBV-706 as a monotherapy at or below the maximum tolerated dose (MTD) maximum administered dose (MAD), as part of an approximately 1 year treatment period. Part 4b: ABBV-706 Monotherapy Dose Expansion NECs ABBV-706 Participants with R/R neuroendocrine carcinomas (NECs) will receive IV Infused ABBV-706 as a monotherapy at or below the MTD/MAD, as part of an approximately 1 year treatment period. Part 3b: ABBV-706 + Platinum Chemotherapy Cisplatin Participants will receive ABBV-706 in combination with carboplatin or cisplatin, as part of an approximately 1 year treatment period. Part 3b: ABBV-706 + Platinum Chemotherapy Carboplatin Participants will receive ABBV-706 in combination with carboplatin or cisplatin, as part of an approximately 1 year treatment period.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Adverse Events (AE) Up to Approximately 2 Years 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.
Maximum Observed Serum/Plasma Concentration (Cmax) of ABBV-706 Up to Approximately 2 Years Maximum observed serum/plasma concentration of ABBV-706.
Time to Cmax (Tmax) of ABBV-706 Up to Approximately 2 Years Time to Cmax of ABBV-706.
Terminal Phase Elimination Half-Life (t1/2) of ABBV-706 Up to Approximately 2 Years Terminal phase elimination half-life (t1/2) of ABBV-706.
Area Under the Serum/Plasma Concentration-Time Curve (AUC) of ABBV-706 Up to Approximately 2 Years Area under the serum/plasma concentration-time curve of ABBV-706.
Antidrug Antibodies (ADAs) Up to Approximately 2 Years Incidence and concentration of anti-drug antibodies.
Neutralizing Antibodies (nAbs) Up to Approximately 2 Years Incidence and concentration of neutralizing antibodies.
Percentage of Participants with Objective Response, for Participants with Extracranial Solid Tumors Up to Approximately 2 Years 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.
Recommended Phase 2 Dose (RP2D) of ABBV-706 Up to Approximately 2 Years 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.
Percentage of Participants with Objective Response for Participants with Central Nervous System (CNS) Tumors Up to Approximately 2 Years 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.
Duration of response (DOR) for Participants with Confirmed CR/PR Up to Approximately 2 Years 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.
Percentage of Participants with Clinical Benefit Up to Approximately 2 Years Clinical benefit is defined as a participant achieving CR/PR, or Stable Disease (SD).
Progression-Free Survival (PFS) Up to Approximately 2 Years 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.
Overall survival (OS) Up to Approximately 2 Years OS is defined as time from first study treatment to death due to any cause.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (65)
Hospital Santa Creu i Sant Pau /ID# 257294
🇪🇸Barcelona, Spain
Hospital Universitario Ramon y Cajal /ID# 257291
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz /ID# 257295
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre /ID# 258658
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro /ID# 258657
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio /ID# 256940
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Valencia /ID# 257290
🇪🇸Valencia, Spain
Hospital Universitario Vall d'Hebron /ID# 258659
🇪🇸Barcelona, Spain
Henry Ford Hospital /ID# 246648
🇺🇸Detroit, Michigan, United States
Shanghai Chest Hospital /ID# 270036
🇨🇳Shanghai, Shanghai, China
Banner MD Anderson Cancer Ctr /ID# 260129
🇺🇸Gilbert, Arizona, United States
City Of Hope Comprehensive Cancer Center /ID# 271295
🇺🇸Duarte, California, United States
City of Hope Orange County Lennar Foundation Cancer Center /ID# 259884
🇺🇸Irvine, California, United States
Yale New Haven Hospital /ID# 246647
🇺🇸New Haven, Connecticut, United States
Georgetown University Hospital /ID# 255352
🇺🇸Washington, District of Columbia, United States
University of Chicago /ID# 256334
🇺🇸Chicago, Illinois, United States
Fort Wayne Medical Oncology and Hematology, Inc /ID# 260130
🇺🇸Fort Wayne, Indiana, United States
University of Iowa Hospitals and Clinics /ID# 246638
🇺🇸Iowa City, Iowa, United States
Barbara Ann Karmanos Cancer In /ID# 261799
🇺🇸Detroit, Michigan, United States
START Midwest /ID# 251257
🇺🇸Grand Rapids, Michigan, United States
St. Luke's Hosp. of Kansas City /ID# 259958
🇺🇸Kansas City, Missouri, United States
Washington University-School of Medicine /ID# 246286
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center-Koch Center /ID# 246303
🇺🇸New York, New York, United States
Duke Cancer Center /ID# 246285
🇺🇸Durham, North Carolina, United States
UH Cleveland Medical Center /ID# 246641
🇺🇸Cleveland, Ohio, United States
Univ Oklahoma HSC /ID# 250884
🇺🇸Oklahoma City, Oklahoma, United States
Tennessee Oncology, PLLC /ID# 246283
🇺🇸Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center /ID# 246287
🇺🇸Houston, Texas, United States
South Texas Accelerated Research Therapeutics /ID# 248946
🇺🇸San Antonio, Texas, United States
University of Utah /ID# 246640
🇺🇸Salt Lake City, Utah, United States
Northwest Medical Specialties - Tacoma /ID# 262801
🇺🇸Tacoma, Washington, United States
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, Australia
Cancer Hospital - Chinese Academy Of Medical Sciences /ID# 270044
🇨🇳Beijing, Beijing, China
Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 270038
🇨🇳Wuhan, Hubei, China
The first hospital of China medical University /ID# 270041
🇨🇳Shenyang, Liaoning, China
Shanghai East Hospital /ID# 268615
🇨🇳Shanghai, Shanghai, China
Institut Bergonie /ID# 258655
🇫🇷Bordeaux, Gironde, France
Institut Gustave Roussy /ID# 260334
🇫🇷Villejuif Cedex, Val-de-Marne, France
Institut Régional du Cancer Montpellier /ID# 265086
🇫🇷Montpellier, France
Klinikum der Universitaet Muenchen - Campus Innenstadt /ID# 259412
🇩🇪Munich, Bayern, Germany
Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin /ID# 259413
🇩🇪Berlin, Germany
Technische Universitat Dresden /ID# 259414
🇩🇪Dresden, Germany
Rambam Health Care Campus /ID# 255059
🇮🇱Haifa, H_efa, Israel
The Chaim Sheba Medical Center /ID# 254915
🇮🇱Ramat Gan, Tel-Aviv, Israel
Hadassah Medical Center-Hebrew University /ID# 255147
🇮🇱Jerusalem, Israel
Istituto Europeo Di Oncologia /ID# 256804
🇮🇹Milan, Milano, Italy
Fondazione IRCCS San Gerardo dei Tintori - Ospedale San Gerardo /ID# 258228
🇮🇹Monza, Monza E Brianza, Italy
National Cancer Center Hospital East /ID# 259417
🇯🇵Kashiwa-shi, Chiba, Japan
National Hospital Organization Shikoku Cancer Center /ID# 261279
🇯🇵Matsuyama, Ehime, Japan
Hokkaido Cancer Center /ID# 261278
🇯🇵Sapporo-shi, Hokkaido, Japan
Kyoto University Hospital /ID# 259419
🇯🇵Kyoto-shi, Kyoto, Japan
Shizuoka Cancer Center /ID# 261277
🇯🇵Sunto-gun, Shizuoka, Japan
National Cancer Center Hospital /ID# 259418
🇯🇵Chuo-ku, Tokyo, Japan
The Cancer Institute Hospital Of JFCR /ID# 260132
🇯🇵Koto-ku, Tokyo, Japan
Wakayama Medical University Hospital /ID# 260131
🇯🇵Wakayama-shi, Wakayama, Japan
National Cancer Center /ID# 248938
🇰🇷Goyang-si, Gyeonggido, Korea, Republic of
CHA Bundang Medical Center /ID# 248939
🇰🇷Seongnam, Gyeonggido, Korea, Republic of
Chonnam National University Hwasun Hospital /ID# 248943
🇰🇷Hwasun-gun, Jeonranamdo, Korea, Republic of
Seoul National University Hospital /ID# 248940
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Samsung Medical Center /ID# 248936
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Yonsei University Health System Severance Hospital /ID# 248937
🇰🇷Seoul, Korea, Republic of
Hospital HM Nou Delfos /ID# 264851
🇪🇸Barcelona, Spain