Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (Fc?RIIB), in Combination with Pembrolizumab in Subjects with Advanced Solid Tumors Previously Treated with Anti-PD1 or AntiPDL1 Antibodies
- Conditions
- Advanced solid tumors who have relapsed or are refractory to anti-PD1 or anti-PDL1 therapy.MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001923-11-SE
- Lead Sponsor
- BioInvent International AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 90
1. Is willing and able to provide written informed consent for the trial.
2. Is at = 18 years of age on day of signing informed consent.
3. Has a histologically confirmed advanced solid tumor. Subjects must have received at least 2 doses of an approved anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies, and have documented progression on or within 12 weeks from the last dose of anti-PD-1/L1 mAb.
4. Has received standard of care or is intolerant of, refuses, or is not eligible for standard of care antineoplastic therapy.
5. Has at least 1 measurable disease lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
6. Is willing to safely undergo tissue biopsies of involved tissue, if required. However, 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.
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 following 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.
7. Has a life expectancy of =12 weeks.
8. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1.
9. Has adequate organ function as confirmed by laboratory values listed in the main body of the protocol.
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 portion of the trial.
1. Cohort 1 (Non-small- cell lung cancer):
a.For subjects whose tumor has PD-L1 =50%: Required prior therapies will include anti-PD-1 therapy as monotherapy. Prior standard of care (SOC) chemotherapy will be allowed but not required.
b. For tumors with unknown PD-L1 or PD-L1 <50% , required prior therapies will include anti-PD 1/PD-L1 therapy and SOC chemotherapy either combined with anti PD-1/PD-L1 therapy or given separately.
c. For subjects with known anaplastic lymphoma kinase (ALK), ROS proto- oncogene 1, receptor tyrosine kinase (ROS1) or epidermal growth factor receptor (EGFR) sensitizing molecular rearrangements, or with BRAF mutations, at least 1 line of targeted therapy will be required in addition to anti-PD-1/PD-L1 therapy.
2. Cohort 2 (Metastatic Melanoma):
a. Required prior therapies will include anti-PD-1 therapy either as monotherapy or as part of a combination regimen.
b. For subjects with a known BRAF V600-activating mutation combination targeted therapy will be required in addition to anti-PD-1/PD-L1 therapy.
3. Cohort 3 (Other Tumor Types):
a. All subjects will require prior anti-PD-1/PD-L1 therapy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45
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 the first dose of study drug. Steroids are allowed as premedication in subjects with allergies to contrast scans.
2. 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 study Screening]); have no newly-onset or worsening symptomatology of brain metastases; and have not required steroids for at least 14 days before study treatment.
3. Has known or suspected hypersensitivity to pembrolizumab or BI-1206 or any of their excipients. Previous isolated IRRs are not to be considered a reason for exclusion unless Grade 4 in intensity.
4. Has cardiac or renal amyloid light-chain amyloidosis.
5. Has received the following:
• Chemotherapy or small molecule products within 4 weeks of first dose of BI-1206.
• Radiotherapy within 2 weeks of 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.
• Immunotherapy within 4 weeks prior to the first dose of BI-1206.
6. Has not recovered from adverse events (AEs) to at least Grade 1 by CTCAE v5.0 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.
7. Has had Grade =3 autoimmune manifestations of previous immune checkpoint inhibitor treatments (e.g. anti-PD1, anti-PDL1 or anti-CTLA4).
8. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
9. 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.
10. 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 last dose of BI-1206 are considered eligible. Highly effective methods of birth control are defined in protocol.
11. Is a male subject with partner(s) of childbearing potential 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 trial and for 12 months after completing treatment). Men with pregnant or lactating partners should be advised to use barrier method contraception (condom plus spermicidal gel).
12. Has had major surgery from which the subject has not yet recovered.
13. Is at high medical risk because of non-malignant systemic disease including severe active infections on treatment with ant
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method