BI-1808 as a Single Agent and With Pembrolizumab (KEYTRUDA® ) in Treatment of Advanced Malignancies(Keynote-D20)
- Conditions
- Advanced Malignancies
- Registration Number
- NCT04752826
- Lead Sponsor
- BioInvent International AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Target population:<br><br>Phase 1, Parts A and Part B of the trial will recruit subjects with all types of<br>malignancies whose tumors have progressed after standard anticancer treatment.<br><br>Phase 2a, Parts A and Part B of the trial will recruit patients with NSCLC, OC, and CTCL<br>(specifically MF or SS).<br><br>Inclusion Criteria:<br><br> 1. Is willing and able to provide written informed consent for the trial.<br><br> 2. Is =18 years of age on the day of signing informed consent.<br><br> 3. Has a histologically confirmed advanced malignancy. Subjects with CTCL [MF or SS]<br> who satisfy the Phase 2a, Cohort 3-specific eligibility criteria may be enrolled<br> into the Phase 1 part of the study.<br><br> 4. Is intolerant of, refuses, or is not eligible for standard antineoplastic therapy.<br><br> 5. Has at least 1 measurable disease lesion as defined by RECIST.<br><br> 6. Is able to safely undergo a baseline tumor tissue biopsy prior to first dose of<br> BI-1808 (on non previously irradiated lesions only). The biopsy must be performed at<br> least 4 weeks following the last dose of tumor directed therapy.<br><br> 7. Has a life expectancy of =12 weeks.<br><br> 8. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.<br><br> 9. Has adequate organ function as confirmed by laboratory values.<br><br>Phase 2:<br><br>Inclusion criteria in addition to above.<br><br>Cohort 1 and Cohort 4 (NSCLC):<br><br> 1. For subjects whose tumors have programmed death-ligand 1 (PD-L1) =50%: Required<br> prior therapies will include anti-PD-1 therapy as monotherapy. Prior standard of<br> care chemotherapy will be allowed but not required.<br><br> 2. For tumors with unknown PD-L1 or PD-L1 <50%, required prior therapies will include<br> anti PD 1/PD-L1 therapy and standard of care chemotherapy either combined with anti<br> PD 1/PD-L1 therapy or given separately.<br><br> 3. For subjects with known anaplastic lymphoma kinase, ROS proto-oncogene 1, receptor<br> tyrosine kinase (ROS1) or epidermal growth factor receptor sensitizing molecular<br> rearrangements, 1 line of targeted therapy will be required in addition to<br> anti-PD-1/PD-L1 therapy.<br><br>Cohort 2 and Cohort 5 (OC):<br><br> 1. Histologically confirmed and documented recurrent ovarian, fallopian tube, and<br> peritoneal cancer.<br><br> 2. Platinum-resistant OC (defined as relapsing within 6 months after the last<br> administration of platinum-based chemotherapy) or platinum-refractory OC (defined as<br> progressing while on a platinum-based chemotherapy).<br><br> 3. At least treated with 1 line of platinum-based chemotherapy.<br><br> 4. Prior treatment with poly-ADP ribose polymerase inhibitors is allowed.<br><br>Cohort 3 (CTCL - MF or SS)<br><br> 1. Stage IB-IV MF or SS with failure of at least 1 systemic therapy.<br><br> 2. No current large cell transformation.<br><br> 3. Prior therapy - No prior allo hematopoietic stem cell transplantation (HSCT); >90<br> days since auto HSCT; >4 weeks since systemic therapy and >2 weeks since<br> skin-directed therapy.<br><br> 4. Stable doses of systemic steroids (=20 mg prednisone equivalent) and of<br> low-to-medium potency topical steroids permitted (no change in preceding 4 weeks).<br><br> 5. Prior lines with mogamulizumab or vorinostat are allowed<br><br>Exclusion Criteria:<br><br> 1. Needs doses of prednisolone >10 mg daily (or equipotent doses of other<br> corticosteroids) while on the trial other than as premedication.<br><br> 2. Has known active central nervous system (CNS) metastases and/or carcinomatous<br> meningitis.<br><br> 3. Has known or suspected hypersensitivity to BI-1808 or pembrolizumab<br><br> 4. Has cardiac or renal amyloid light-chain amyloidosis.<br><br> 5. Has received the following:<br><br> 1. Chemotherapy or small molecule products within 4 weeks of first dose of<br> BI-1808.<br><br> 2. Radiotherapy within 2 weeks of first dose of BI-1808. A 1-week washout is<br> permitted for palliative radiation (=2 weeks of radiotherapy) for non-CNS<br> disease. Subjects who have previously had radiation pneumonitis are not<br> allowed.<br><br> 3. Immunotherapy within 4 weeks prior to the first dose of BI-1808.<br><br> 6. Has not recovered from AEs to at least Grade 1 by NCI CTCAE<br><br> 7. Has had Grade =3 autoimmune manifestations of previous immune checkpoint inhibitor<br> treatments (eg, anti-PD-1, anti-PD-L1, or anti-CTLA-4).<br><br> 8. Has a history of (noninfectious) pneumonitis that required steroids or has current<br> pneumonitis.<br><br> 9. Has an active, known, or suspected autoimmune disease.<br><br> 10. Is a female subject and has the ability to become pregnant (or already pregnant or<br> lactating/breastfeeding). However, those female subjects who have a negative serum<br> or urine pregnancy test before enrollment and agree to use a highly effective method<br> of birth control for 4 weeks before entering the trial, during the trial, and for 12<br> months after last dose of BI-1808, are considered eligible.<br><br> 11. Is a male subject with partner(s) of childbearing potential (unless he agrees to<br> take measures not to father children by using 1 form of highly effective<br> contraception [condom plus spermicide gel] during the trial and for 12 months after<br> completing treatment).<br><br> 12. Has had major surgery from which the subject has not yet recovered.<br><br> 13. Is at high medical risk because of nonmalignant systemic disease including severe<br> active infections on treatment with antibiotics, antifungals, or antivirals.<br><br> 14. Has presence of chronic graft versus host disease.<br><br> 15. Has had an allogenic tissue/solid organ transplant.<br><br> 16. Has known human immunodeficiency (HIV) and/or history of hepatitis B or C<br> infections, or has a positive test for HIV antibody, hepatitis B antigen/hepatitis B<br> virus DNA or hepatitis C antibody or RNA.<br><br> 17. Has a history of active tuberculosis (Bacillus tuberculosis).<br><br> 18. Has received a live vaccine within 30 days before the first dose of study treatment.<br><br> 19. Has uncontrolled or significant cardiovascular disease.<br><br> 20. Has a known psychiatric or substance abuse disorder that would interfere with the<br> subject's ability to cooperate with the requirements of the trial.<br><br> 21. Has a history or current evidence of any condition, therapy, or laboratory<br> abnormality that might confound the results of the trial, interfere with the<br> subject's participation for the full duration of the trial, or is not in the best<br> interest of the subject to participate, in the opinion of the treating Investigator.<br><br> 22. Is participating or planning to participate in another interventional clinical<br> trial, or has participated in a trial of an investigational agent or has used an<br> investigational device within 4 weeks prior to first dose of study drug.<br><br> 23. Has a known additional malignancy of another type, with the exception of adequately<br> treated cone biopsied carcinoma in situ (eg, breast carcinoma, cervical cancer in<br> situ) and basal or squamous cell carcinoma of the skin. Male subjects with<br> asymptomatic prostate cancer without known metastatic disease and with no<br> requirement for therapy or requiring only hormonal therapy and with normal<br> prostate-specific antigen for >1 year prior to start of trial therapy are eligible.<br><br> 24. Has a diagnosis of primary or acquired immunodeficiency disorder or taking any other<br> form of immunosuppressive therapy within 7 days prior the
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Documenting AEs and SAEs and determining causality in relation to BI-1808 and/or pembrolizumab;Identify DLTs, determine the maximum tolerated dose and select a recommended Phase 2 dose (RP2D) of BI-1808, given via intravenous (IV) infusion, as a single agent (Phase 1, Part A), and in combination with pembrolizumab (Phase 1, Part B)
- Secondary Outcome Measures
Name Time Method Evaluation of PK parameters for BI-1808. Maximum observed plasma concentration (Cmax);Evaluation of ADA response to BI-1808 in serum with validated method;Measurement of TNFR2 receptor occupancy on CD14+ and/CD16+ cells in serum with validated method