Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcγRIIB), in Combination with Pembrolizumab in Subjects with Advanced Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BioInvent International AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 May 2020 → ongoing

Decision date (initial)

2026-01-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BioInvent International AB

External identifiers

EU CT number

2023-509846-36-00

EudraCT number

2019-001923-11

ClinicalTrials.gov

NCT04219254

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Pharmacokinetic, Pharmacogenetic, Safety, Dose response

The primary objectives/endpoints of this trial are to:
1. Assess the safety and tolerability profile of increasing doses of BI-1206, administered intravenously (IV) or subcutaneously (SC), in combination with pembrolizumab in subjects with advanced solid tumors. Phase 1:
2. Identify dose-limiting toxicities (DLTs), determine the maximum tolerated dose (MTD) and select a signal-seeking Phase 2a dose of BI-1206, given via IV infusion or SC injection in combination with pembrolizumab (administered at the standard dose of 200 mg every 3 weeks) to subjects with advanced solid tumors who are experiencing disease progression and have been previously treated with anti-PD1 or PDL1 antibodies.
Phase 2a:
• Select a recommended Phase 2 dose (RP2D) of BI-1206 given via SC injection in combination with pembrolizumab to subjects with non-small cell lung cancer (NSCLC) and uveal melanoma.
• Document the frequency and occurrence of adverse events (AEs), treatment-emergent adverse events (TEAEs), and immune-related AEs (irAEs).

Secondary objectives 3

1. Study the PK profile of BI-1206 administered IV or SC in combination with pembrolizumab in subjects with advanced solid tumors.
2. Assess the immunogenicity of BI-1206, administered IV or SC, in subjects with advanced solid tumors, when given in combination with pembrolizumab.
3. Evaluate the effect of BI-1206 administered IV or SC in combination with pembrolizumab on CD32b receptor occupancy on B cells in subjects with advanced solid tumors.

Conditions and MedDRA coding

Advanced Solid Tumors

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. For Phase 1: Is willing and able to provide written informed consent for the trial.
2. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1.
3. Has adequate organ function as confirmed by laboratory values listed in the main body of the protocol.
4. Expansion Cohort-specific Inclusion Criteria: In addition to the general inclusion criteria above, subjects must also meet the criteria for the specific cohort. Additional requirements will be added based on learnings from subjects enrolled in the Phase 1 part of the trial. 3. Cohort 3 (Other Tumor Types): a. All subjects will require prior anti-PD-1/PD-L1 therapy.
5. For Phase 2a: Expansion Cohort-specific Inclusion Criteria: Note: Phase 2a will enroll subjects who are treatment-naïve. Inclusion criteria No.3, No.4 and No.6 do not apply to patients enrolled in the Phase 2a expansion cohorts. Subjects diagnosed with uveal melanoma who have received previous treatment with tebentafusp and/or liver directed therapy are allowed. In addition to the general inclusion criteria above (except for criteria n.3, n.4, and No.6), subjects must also meet the criteria for the tissue-specific cohort. 2. Cohort 2 (uveal Melanoma): a.Has a histologically confirmed diagnosis of advanced or metastatic uveal melanoma. b.Has a PD-L1 positive (TPS≥1%) tumor as determined by IHC at a local laboratory. c.Has not received prior systemic immunotherapy or chemotherapy treatment for their advanced/metastatic uveal melanoma. Subjects who have received previous treatment with tebentafusp and/or liver directed therapy are allowed. d.Has provided formalin-fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of advanced or metastatic disease has been made and from a site not previously irradiated to perform biomarker analysis
6. For Phase 2a: Expansion Cohort-specific Inclusion Criteria: Note: Phase 2a will enroll subjects who are treatment-naïve. Inclusion criteria No.3, No.4 and No.6 do not apply to patients enrolled in the Phase 2a expansion cohorts. Subjects diagnosed with uveal melanoma who have received previous treatment with tebentafusp and/or liver directed therapy are allowed. In addition to the general inclusion criteria above (except for criteria n.3, n.4, and No.6), subjects must also meet the criteria for the tissue-specific cohort. 1. Cohort 1 (NSCLC): a.Have a histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC and not have an EGFR sensitizing (activating) mutation or an ALK translocation. b. Has a PD-L1 positive (TPS≥50%) tumor as determined by IHC at a local laboratory. c. Has not received prior systemic immunotherapy or chemotherapy treatment for their advanced/metastatic NSCLC. d. Has provided formalin-fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of advanced or metastatic disease has been made and from a lesion not previously irradiated to perform biomarker analysis.
7. Is at ≥ 18 years of age on the day of signing informed consent.
8. Has a histologically confirmed advanced solid tumor. Subjects must have received at least 2 doses of an approved anti-PD-1/PD-L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies, and must have documented progression on or within 12 weeks from the last dose of anti-PD-1/PD-L1 mAb.
9. Has received standard of care or is intolerant of, refuses, or is not eligible for standard of care antineoplastic therapy.
10. Has at least 1 measurable disease lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST).
11. Is willing to provide an archival tumor tissue sample or newly obtained [core, incisional, OR excisional] biopsy of a tumor lesion not previously irradiated. If the Investigator considers that a tissue biopsy is not safe and/or not technically feasible, then the subject will not be required to undergo the biopsy. However, in SC cohorts of Phase 2a the tissue biopsy from Screening is mandatory. a. The Screening biopsy must be performed prior to the first dose of BI-1206 (on non-previously irradiated lesions only), and at least 4 weeks after the last dose of tumor-directed therapy. The biopsy at Screening can be replaced with a formalin- fixed archival tumor tissue sample collected from a previous standard of care biopsy, provided that the biopsy was performed after the subject's last tumor- directed therapy and prior to study entry. Subjects who do not have an archival tissue sample at Screening may still be enrolled in the study.
12. Has a life expectancy of ≥12 weeks.
13. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to enrollment.
14. Participants with history of HCV infection are eligible if HCV viral load is undetectable at Screening.

Exclusion criteria 21

1. Needs doses of prednisolone >10 mg daily (or equipotent doses of other corticosteroids) while on the trial other than as premedication. During the Screening period, doses of up to 20 mg/day may be given but the dose must be reduced to 10 mg/day within 7 days prior to the first dose of study drug. Steroids are allowed as premedication in subjects with allergies to contrast scans.
2. Is a female subject and has the ability to become pregnant (or already pregnant or lactating/ breastfeeding). Those female subjects who have a negative serum or urine pregnancy test before enrollment and agree to use a highly effective method of birth control for 4 weeks before entering the trial, during the trial and for 12 months after the last dose of BI-1206 are considered eligible. Highly effective methods of birth control are defined in protocol.
3. Male subjects with partner(s) of childbearing potential are excluded unless the male partner agrees to use a barrier method of contraception (condom plus spermicidal gel) with the female partner(s) who are using one highly effective method of contraception during the study and for 12 months after completing treatment.
4. Has had major surgery from which the subject has not yet recovered.
5. Is at high medical risk because of non-malignant systemic disease including severe active infections on treatment with antibiotics, antifungals or antivirals.
6. Has presence of chronic graft versus host disease.
7. Has had an allogenic tissue/solid organ transplant.
8. Has known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
9. Has a history of active tuberculosis (bac. tuberculosis).
10. Has received a live vaccine within 30 days before the first dose of study treatment. COVID-19 vaccines based on viral RNA or protein fragments, or killed viruses, are allowed. COVID 19 vaccines based on live replicating viral or bacterial vectors are not allowed.
11. Has uncontrolled or significant cardiovascular disease as per protocol definition.
12. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated CNS metastases may participate provided they are radiologically stable (without evidence of progression for at least 4 weeks by repeat imaging [performed during Screening]); have no newly-onset or worsening symptomatology of brain metastases; and have not required steroids for at least 14 days before study treatment.
13. Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study.
14. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or lead to participation not being in the best interest of the subject, in the opinion of the Investigator.
15. Is participating or planning to participate in another interventional clinical trial, or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug.
16. Has known or suspected hypersensitivity to pembrolizumab or BI1206 or any of their excipients. Previous isolated IRRs are not to be considered a reason for exclusion unless Grade 4 in intensity.
17. Has cardiac or renal amyloid light-chain amyloidosis.
18. Has received radiotherapy within 2 weeks of the first dose of BI-1206. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) for non-CNS disease. Subjects who have previously had radiation pneumonitis are not allowed.
19. Has not recovered from adverse events (AEs) to at least Grade 1 by CTCAE v5.0 (or higher) due to prior anti-cancer therapies. Exceptions are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator should not exclude the subject. Subjects with ≤Grade 2 neuropathy may be eligible, after discussion with the Medical Monitor.
20. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
21. Has an active, known or suspected autoimmune disease. Subjects with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, mild psoriasis, or alopecia not requiring systemic treatment), or conditions not expected to recur in the absence of an external trigger will be permitted to participate.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Documentation of AEs and SAEs (graded according to the NIH National Cancer Institute, Division of Cancer Treatment and Diagnosis: Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 or higher, clinically significant laboratory parameters and physical findings, as well as their causality to BI-1206 and/or pembrolizumab administration.
2. In Phase 1, identify DLT occurrence: Determination of signal-seeking dose and the MTD or maximum administered dose of BI-1206, based on the modified mTPI-2 design.
3. In Phase 2a: Determination of the RP2D

Secondary endpoints 3

1. Determination of standard PK parameters (i.e., AUC, Cmax, Tmax, and terminal half-life [t½]) for BI-1206.
2. Measurement of ADA response to BI-1206.
3. Blood exploratory samples. Measurement of CD32b receptor occupancy on B cells.

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BioInvent International AB

Sponsor organisation

BioInvent International AB

Address

Ideongatan 1 A, Lunds Allhelgonafors. Lunds Allhelgonafors.

City

Lund

Postcode

223 62

Country

Sweden

Scientific contact point

Organisation

BioInvent International AB

Contact name

Ingunn Munch Lindvig

Public contact point

Organisation

BioInvent International AB

Contact name

Ingunn Munch Lindvig

Third parties 9

Locations

5 EU/EEA countries · 18 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 41 files

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

Application history

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