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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05599984




Registration number
NCT05599984
Ethics application status
Date submitted
28/10/2022
Date registered
31/10/2022
Date last updated
4/06/2024

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
M23-385
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ABBV-706
Treatment: Drugs - Cisplatin
Treatment: Drugs - Budigalimab
Treatment: Drugs - Carboplatin

Experimental: Part 1: ABBV-706 Monotherapy Dose Escalation - Participants will receive escalating doses of ABBV-706 until doses for optimization are determined, as part of an approximately 1 year treatment period.

Experimental: Part 2: ABBV-706 Monotherapy Dose Optimization and Expansion - 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..

Experimental: Part 3a: ABBV-706 + Budigalimab - Participants will receive ABBV-706 in combination with budigalimab, as part of an approximately 1 year treatment period.

Experimental: Part 3b: ABBV-706 + Platinum Chemotherapy - Participants will receive ABBV-706 in combination with carboplatin or cisplatin, as part of an approximately 1 year treatment period.

Experimental: Part 4a: ABBV-706 Monotherapy Dose Expansion CNS Tumors - 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.

Experimental: Part 4b: ABBV-706 Monotherapy Dose Expansion NECs - 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.


Treatment: Drugs: ABBV-706
Intravenous (IV) Infusion

Treatment: Drugs: Cisplatin
Intravenous infusion

Treatment: Drugs: Budigalimab
IV Infusion

Treatment: Drugs: Carboplatin
Intravenous infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Adverse Events (AE)
Timepoint [1] 0 0
Up to Approximately 2 Years
Primary outcome [2] 0 0
Maximum Observed Serum/Plasma Concentration (Cmax) of ABBV-706
Timepoint [2] 0 0
Up to Approximately 2 Years
Primary outcome [3] 0 0
Time to Cmax (Tmax) of ABBV-706
Timepoint [3] 0 0
Up to Approximately 2 Years
Primary outcome [4] 0 0
Terminal Phase Elimination Half-Life (t1/2) of ABBV-706
Timepoint [4] 0 0
Up to Approximately 2 Years
Primary outcome [5] 0 0
Area Under the Serum/Plasma Concentration-Time Curve (AUC) of ABBV-706
Timepoint [5] 0 0
Up to Approximately 2 Years
Primary outcome [6] 0 0
Antidrug Antibodies (ADAs)
Timepoint [6] 0 0
Up to Approximately 2 Years
Primary outcome [7] 0 0
Neutralizing Antibodies (nAbs)
Timepoint [7] 0 0
Up to Approximately 2 Years
Primary outcome [8] 0 0
Percentage of Participants with Objective Response, for Participants with Extracranial Solid Tumors
Timepoint [8] 0 0
Up to Approximately 2 Years
Primary outcome [9] 0 0
Recommended Phase 2 Dose (RP2D) of ABBV-706
Timepoint [9] 0 0
Up to Approximately 2 Years
Primary outcome [10] 0 0
Percentage of Participants with Objective Response for Participants with Central Nervous System (CNS) Tumors
Timepoint [10] 0 0
Up to Approximately 2 Years
Primary outcome [11] 0 0
Duration of response (DOR) for Participants with Confirmed CR/PR
Timepoint [11] 0 0
Up to Approximately 2 Years
Primary outcome [12] 0 0
Percentage of Participants with Clinical Benefit
Timepoint [12] 0 0
Up to Approximately 2 Years
Primary outcome [13] 0 0
Progression-Free Survival (PFS)
Timepoint [13] 0 0
Up to Approximately 2 Years
Primary outcome [14] 0 0
Overall survival (OS)
Timepoint [14] 0 0
Up to Approximately 2 Years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/12/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
17/05/2027
Actual
Sample size
Target
350
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse /ID# 259087 - Camperdown
Recruitment hospital [2] 0 0
The Kinghorn Cancer Centre /ID# 260874 - Darlinghurst
Recruitment hospital [3] 0 0
Austin Health and Ludwig Institute for Cancer Research /ID# 255174 - Heidelberg
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Ctr /ID# 259197 - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oklahoma
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Germany
State/province [17] 0 0
Dresden
Country [18] 0 0
Israel
State/province [18] 0 0
H_efa
Country [19] 0 0
Israel
State/province [19] 0 0
Tel-Aviv
Country [20] 0 0
Israel
State/province [20] 0 0
Jerusalem
Country [21] 0 0
Japan
State/province [21] 0 0
Chiba
Country [22] 0 0
Japan
State/province [22] 0 0
Ehime
Country [23] 0 0
Japan
State/province [23] 0 0
Hokkaido
Country [24] 0 0
Japan
State/province [24] 0 0
Kyoto
Country [25] 0 0
Japan
State/province [25] 0 0
Shizuoka
Country [26] 0 0
Japan
State/province [26] 0 0
Tokyo
Country [27] 0 0
Japan
State/province [27] 0 0
Wakayama
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Gyeonggido
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Jeonranamdo
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Seoul Teugbyeolsi
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Seoul
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid
Country [33] 0 0
Spain
State/province [33] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05599984
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
844-663-3742
Fax 0 0
Email 0 0
abbvieclinicaltrials@abbvie.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05599984