Inclusion Criteria:
1. Is willing and able to provide written informed consent for the trial.
2. Is ≥18 years of age on the day of signing informed consent.
3. Has a histologically confirmed advanced malignancy. Subjects with CTCL [MF or SS]
who satisfy the Phase 2a, Cohort 3-specific eligibility criteria may be enrolled
into the Phase 1 part of the study.
4. Is intolerant of, refuses, or is not eligible for standard antineoplastic therapy.
5. Has at least 1 measurable disease lesion as defined by RECIST.
6. Is able to safely undergo a baseline tumor tissue biopsy prior to first dose of
BI-1808 (on non previously irradiated lesions only). The biopsy must be performed at
least 4 weeks following the last dose of tumor directed therapy.
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.
Phase 2a Expansion Cohort-Specific
Inclusion Criteria:
Ovarian Cancer:
Histologically confirmed and documented recurrent ovarian, fallopian tube, and peritoneal
cancer.
TCL:
1. histologically confirmed diagnosis. 2. Stable doses of systemic steroids (≤20 mg prednisone equivalent) and of
low-to-medium potency topical steroids permitted (no change in preceding 4 weeks).
3. Stage IB-IV with failure of at least 1 systemic therapy.
4. No current large cell transformation for subjects with CTCL.
5. Prior therapy
- - No prior allo hematopoietic stem cell transplantation (HSCT); >90
days since auto HSCT; >4 weeks since systemic therapy and >2 weeks since
skin-directed therapy.
6. Stable doses of systemic steroids (≤20 mg prednisone equivalent) and of
low-to-medium potency topical steroids permitted (no change in preceding 4 weeks).
7. Previous systemic therapies include brentuximab vedotin, bexarotene, extracorporeal
photopheresis (ECP), methotrexate, mogamulizumab, romidepsin, vorinostat, or
systemic therapy with localized radiation treatment or skin-directed therapy.
Melanoma:
1. Histologically confirmed diagnosis of unresectable or metastatic melanoma.
Subjects in Part A:
2. Required prior therapies will include anti-programmed death-ligand 1 (PD-1) therapy
either as monotherapy or as part of a combination regimen.
3. For subjects with a known BRAF V600-activating mutation combination targeted therapy
will be required in addition to anti-PD-1/programmed death-ligand 1 (PD-L1) therapy.
Subjects in part B:
4. Subjects with prior lines of treatment are not eligible.
All Tumor Types:
Locally advanced unresectable, recurrent or metastatic immune checkpoint inhibitor-naïve
solid tumors, likely to benefit from immune checkpoint inhibitor treatment, based on
Investigator opinion.
b. Subjects must have received prior standard therapy appropriate for their tumor type
and stage of disease, or in the opinion of the Investigator, would be unlikely to
tolerate or derive clinical benefit from appropriate standard of care therapy.
c. Subjects with known activation mutations must have prior target therapy.
Exclusion Criteria:
1. Needs doses of prednisolone >10 mg daily (or equipotent doses of other
corticosteroids) while on the trial other than as premedication.
2. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis.
3. Has known or suspected hypersensitivity to BI-1808 or pembrolizumab. 4. Has cardiac or renal amyloid light-chain amyloidosis.
5. Has received the following:
1. Chemotherapy or small molecule products within 4 weeks of first dose of
BI-1808.
2. Radiotherapy within 2 weeks of first dose of BI-1808. 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.
3. Immunotherapy within 4 weeks prior to the first dose of BI-1808.
6. Has not recovered from AEs to at least Grade 1 by NCI CTCAE. 7. Has had Grade ≥3 autoimmune manifestations of previous immune checkpoint inhibitor
treatments (eg, anti-PD-1, anti-PD-L1, or anti-CTLA-4).
8. Has a history of (noninfectious) pneumonitis that required steroids or has current
pneumonitis.
9. Has an active, known, or suspected autoimmune disease.
10. Is a female subject and has the ability to become pregnant (or already pregnant or
lactating/breastfeeding). However, 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-1808, are considered eligible.
11. Is a male subject with partner(s) of childbearing potential (unless he agrees to
take measures not to father children by using 1 form of highly effective
contraception [condom plus spermicide gel] during the trial and for 12 months after
completing treatment).
12. Has had major surgery from which the subject has not yet recovered.
13. Is at high medical risk because of nonmalignant systemic disease including severe
active infections on treatment with antibiotics, antifungals, or antivirals.
14. Has presence of chronic graft versus host disease.
15. Has had an allogenic tissue/solid organ transplant.
16. Has known human immunodeficiency (HIV) and/or history of hepatitis B or C
infections, or has a positive test for HIV antibody, hepatitis B antigen/hepatitis B
virus DNA or hepatitis C antibody or RNA.
17. Has a history of active tuberculosis (Bacillus tuberculosis).
18. Has received a live vaccine within 30 days before the first dose of study treatment.
19. Has uncontrolled or significant cardiovascular disease.
20. Has a known psychiatric or substance abuse disorder that would interfere with the
subject's ability to cooperate with the requirements of the trial.
21. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject's participation for the full duration of the trial, or is not in the best
interest of the subject to participate, in the opinion of the treating Investigator.
22. 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 first dose of study drug.
23. Has a known additional malignancy of another type, with the exception of adequately
treated cone biopsied carcinoma in situ (eg, breast carcinoma, cervical cancer in
situ) and basal or squamous cell carcinoma of the skin. Male subjects with
asymptomatic prostate cancer without known metastatic disease and with no
requirement for therapy or requiring only hormonal therapy and with normal
prostate-specific antigen for >1 year prior to start of trial therapy are eligible.
24. Has a diagnosis of primary or acquired immunodeficiency disorder or taking any other
form of immunosuppressive therapy within 7 days prior the first dose of study drug.
25. Has symptomatic ascites or pleural effusion, requires surgical intervention of
additional medication
