Study to Determine the Safety, Tolerability, Pharmacokinetics and RP2D of ABBV-151 as a Single Agent and in Combination With ABBV-181 in Subjects With Locally Advanced or Metastatic Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Nov 2020 → ongoing

Decision date (initial)

2024-03-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Inc.

External identifiers

EU CT number

2023-508281-15-00

EudraCT number

2018-004303-40

ClinicalTrials.gov

NCT03821935

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Pharmacodynamic

Dose Escalation Phase:
To determine the RP2D of ABBV-151 administered as monotherapy and in combination with budigalimab.
Dose Expansion Phase:
To assess the preliminary efficacy, based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, with the measured objective response rate (ORR) of ABBV-151 in combination with budigalimab in selected tumor types.

Secondary objectives 3

1. Dose Escalation Phase: To assess the safety, tolerability, and PK of ABBV-151 administered as monotherapy and in combination with budigalimab.
2. Dose Expansion Phase: To further assess the preliminary measures of efficacy by RECIST v1.1.
3. Dose Expansion Phase: To assess the safety, tolerability, and PK of ABBV-151 in combination with budigalimab

Conditions and MedDRA coding

Locally Advanced or Metastatic Solid Tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. For Dose Escalation only: Subjects with an advanced solid tumor who are considered refractory to or intolerant of all existing therapy(ies) known to provide a clinical benefit for their condition. Additionally, subjects who have been offered standard therapies and refused, or who are considered ineligible for standard therapies, may be eligible for this study on a case-by-case basis, after discussion with and agreement from the sponsor.
2. Subject has adequate bone marrow, renal, hepatic, and coagulation function.
3. For Dose Escalation only: Subjects with pancreatic adenocarcinoma, urothelial cancer, Hepatocellular carcinoma (HCC), or Head and neck squamous cell carcinoma (HNSCC) who are being considered for the dose escalation cohorts must also meet the histology specific eligibility criteria described below for dose expansion.
4. For Dose Expansion only subjects must meet criteria specific to the type of cancer: Pancreatic adenocarcinoma and have disease progression during or after 1 systemic therapy (including gemcitabine monotherapy or in combination with other agents, FOLFIRINOX [or another regimen including both 5-fluorouracil and oxaliplatin], capecitabine monotherapy or in combination with other agents) administered in the adjuvant, locally advanced, or metastatic setting. Progression on more than 1 prior systemic therapy is not allowed in this cohort. If the therapy was used in an adjuvant setting, disease progression must have occurred within 6 months of completing adjuvant therapy.
5. For Dose Expansion only subjects must meet criteria specific to the type of cancer: Urothelial cancer of the bladder and urinary tract and must have progressed following treatment with a platinum-based regimen (administered in any line of therapy) and a programmed death 1/programmed death ligand 1 (PD1/PDL1) antagonist administered in the recurrent or metastatic setting (progression following a PD1/PDL1 antagonist is defined as unequivocal progression on or within 3 months of the last dose of anti-PD1 or anti-PDL1 therapy).
6. For Dose Expansion only subjects must meet criteria specific to the type of cancer: HCC and must have disease progression during or after 1 prior line of systemic therapy. Progression on more than 1 prior systemic therapy is not allowed in this cohort.
7. For Dose Expansion only subjects must meet criteria specific to the type of cancer: HNSCC (arising from the oral cavity, oropharynx, hypopharynx, or larynx) and must have progressed following treatment with platinum-based regimen (administered in any line of therapy) and a PD1/PDL1 antagonist administered in the recurrent or metastatic setting (progression following a PD1/PDL1 antagonist is defined as unequivocal progression on or within 3 months of the last dose of anti-PD1 or antiPDL1 therapy).
8. For Dose Expansion only subjects must meet criteria specific to the type of cancer: MSS-CRC subjects with microsatellite stable or mismatch repair proficient colorectal adenocarcinoma (as determined by PCR/NGS or IHC, respectively) who have received prior fluorouracil-based combination chemotherapy regimens including oxaliplatin and irinotecan (with or without VEGF and/or EGFR targeted agents).
9. Subjects with progression on or after more than 2 prior systemic therapies in the metastatic setting will not be eligible for this cohort - NSCLC subjects with histologically or cytologically confirmed advanced or metastatic NSCLC who have received 1 prior line of chemotherapy and 1 prior anti-PD- (L)1 antibody, administered either concurrently or sequentially in the metastatic setting. Subjects who have progressed on more than 1 line of chemotherapy in the metastatic setting and/or prior anti-PD (L)1 in the metastatic setting and with known EGFR mutations or ALK gene rearrangements will not be eligible.
10. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
11. For Dose Expansion only: Subjects must have measurable disease per RECIST1.1
12. For Dose Expansion only: All subjects with MSS-CRC, HCC, or pancreatic adenocarcinoma must not have had prior treatment with a PD-1/PDL-1 antagonist in any line of therapy

Exclusion criteria 5

1. Has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy within a period of 5 half-lives or 28 days (whichever is shorter), prior to the first dose of the study drug.
2. Subject has unresolved AEs > Grade 1 from prior anticancer therapy except for alopecia.
3. Has a history of primary immunodeficiency, bone marrow transplantation, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
4. Has a known uncontrolled metastases to the central nervous system (with certain exceptions).
5. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of the study drug.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Dose Escalation Phase: The determination of the RP2D of ABBV-151 as monotherapy and in combination with budigalimab
2. Dose Expansion Phase: Objective Response Rate of CR or PR

Secondary endpoints 4

1. Dose Escalation Phase: Assessment of AEs, serious AEs (SAEs), laboratory parameters, vital signs, electrocardiogram (ECG) results, PK measurements, and antidrug antibody (ADA) measurements.
2. Dose Expansion Phase: Duration of response (DOR)
3. Dose Expansion Phase: Progression-free survival (PFS)
4. Dose Expansion Phase: Assessment of AEs, SAEs, laboratory parameters, vital signs, ECG results, PK, and ADA measurements

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation

AbbVie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Aleksandra Jankielewicz

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Aleksandra Jankielewicz

Third parties 4

Locations

6 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 63 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications