Safety Study of BJ-001, an IL-15 Fusion Protein, for Locally Advanced/Metastatic Solid Tumors

Locally Advanced/Metastatic Solid Tumors Clinical Trial

— FIH  

Official title:

First-in-human (FIH), Open-Label, Phase 1a (Dose Escalation)/Phase 1b (Expansion Cohort) Trial of BJ-001 as a Single Agent and in Combination With Pembrolizumab in Patients With Locally Advanced/Metastatic Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04294576
• Other study ID #: BJ-001-01-001US
• Secondary ID: KEYNOTE-F13
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 4, 2019
• Est. completion date: October 22, 2024

Study information

• Verified date: September 2023
• Source: BJ Bioscience, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and tolerability of BJ-001, a human IL-15 fusion protein, administered via subcutaneous injections, as a single agent and in combination with pembrolizumab in adult patients with Locally Advanced/Metastatic Solid Tumors

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 92
• Est. completion date: October 22, 2024
• Est. primary completion date: April 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Phase 1a patients must have locally advanced or metastatic solid tumors,
• Phase 1b patients must have locally advanced or metastatic and/or non-resectable head and neck squamous cell carcinoma, cholangiocarcinoma, stomach cancer, melanoma, pancreatic cancer, NSCLC (as high expression of aVß3, aVß5, or aVß6 have been reported for these tumors)
• Measurable disease: For Phase 1a patients can have non-measurable or measurable disease. For all other parts: measurable disease defined by RECIST v1.1 is required
• For Phase 1a Part 3 and Phase 1b patients (combination treatment) must be refractory or relapsed to anti-PD-1, anti-PD-L1 or anti-CTLA4 checkpoint inhibitors for all tumor types, For Part 1 and Part 2 of Phase 1a (BJ-001 single agent treatment) both checkpoint inhibitor naïve or refractory/relapsed patients will be considered.
• Patient who have diagnosis for which treatment with pembrolizumab to be enrolled. Patients previously treated with pembrolizumab and who have progressed are eligible. to be enrolled.
• Adequate hematologic function,
• Adequate hepatic function, defined by all of the following:
• Adequate renal function defined by estimated creatinine clearance = 45 mL/min (Cockcroft and Gault formula
• ECOG Performance Status (PS) of 0-2.
• No history of any hematopoietic malignancy.
• No active or history of clinically significant autoimmune disease (as defined by previously requiring immunosuppressive therapy).

Exclusion Criteria:

• Pregnant or nursing females.
• Receipt of any investigational product or any approved anticancer drug(s) or biological product(s) within 4 weeks prior to the first dose of study drug. Exceptions: Hormone replacement therapy, testosterone, or oral contraceptives (LHRH antagonists are allowed).
• Patients previously treated with an anti PD-1/PD-L1 targeting agent who have had any prior history of immune-mediated pneumonitis, any immune-mediated toxicity of = Grade 3,
• Patients with a history of severe allergic or anaphylactic reactions to human mAb therapy or known hypersensitivity.
• Patients with a history of pneumonitis, myocarditis, history of Stevens-Johnson syndrome or toxic epidermal necrolysis.
• Patients who have undergone a bone marrow transplantation, solid organ transplantation, or stem cell transplant.
• Patients with unresolved AEs > Grade 1 from prior anticancer therapy.
• Patients who have received prior interferon or IL-2 therapy less than 4 weeks prior to enrollment.
• Uncontrolled primary central nervous system (CNS) tumors or CNS metastases; based on screening.
• Patients with active autoimmune disease or a documented medical history of autoimmune disease managed by replacement therapy.

Related Conditions & MeSH terms

• Locally Advanced/Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• BJ-001
BJ-001 dosed via SC injection as single agent. One cycle is 6 weeks.
• Pembrolizumab
BJ-001 dosed via SC injection in combination with Pembrolizumab One cycle is 6 weeks.

Locations

Country	Name	City	State
United States	Greenville Hospital System University Medical Center (ITOR)	Greenville	South Carolina
United States	Mount Sinai	New York	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	NEXT Oncology	San Antonio	Texas
United States	Northwest Medical Specialities	Tacoma	Washington

Sponsors (3)

Lead Sponsor	Collaborator
BJ Bioscience, Inc.	Merck Sharp & Dohme LLC, PPD

Country where clinical trial is conducted

United States, 

References & Publications (18)

Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA; National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 Jun 10;36(17):1714-1768. doi: 10.1200/JCO.2017.77.6385. Epub 2018 Feb 14. — View Citation

Caudana P, Nunez NG, De La Rochere P, Pinto A, Denizeau J, Alonso R, Niborski LL, Lantz O, Sedlik C, Piaggio E. IL2/Anti-IL2 Complex Combined with CTLA-4, But Not PD-1, Blockade Rescues Antitumor NK Cell Function by Regulatory T-cell Modulation. Cancer Immunol Res. 2019 Mar;7(3):443-457. doi: 10.1158/2326-6066.CIR-18-0697. Epub 2019 Jan 16. — View Citation

Conlon KC, Lugli E, Welles HC, Rosenberg SA, Fojo AT, Morris JC, Fleisher TA, Dubois SP, Perera LP, Stewart DM, Goldman CK, Bryant BR, Decker JM, Chen J, Worthy TA, Figg WD Sr, Peer CJ, Sneller MC, Lane HC, Yovandich JL, Creekmore SP, Roederer M, Waldmann TA. Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. J Clin Oncol. 2015 Jan 1;33(1):74-82. doi: 10.1200/JCO.2014.57.3329. Epub 2014 Nov 17. — View Citation

Cox L, Larenas-Linnemann D, Lockey RF, Passalacqua G. Speaking the same language: The World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System. J Allergy Clin Immunol. 2010 Mar;125(3):569-74, 574.e1-574.e7. doi: 10.1016/j.jaci.2009.10.060. Epub 2010 Feb 7. — View Citation

Desbois M, Le Vu P, Coutzac C, Marcheteau E, Beal C, Terme M, Gey A, Morisseau S, Teppaz G, Boselli L, Jacques Y, Bechard D, Tartour E, Cassard L, Chaput N. IL-15 Trans-Signaling with the Superagonist RLI Promotes Effector/Memory CD8+ T Cell Responses and Enhances Antitumor Activity of PD-1 Antagonists. J Immunol. 2016 Jul 1;197(1):168-78. doi: 10.4049/jimmunol.1600019. Epub 2016 May 23. — View Citation

Erratum: Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188-195. Blood. 2016 Sep 15;128(11):1533. doi: 10.1182/blood-2016-07-730689. — View Citation

Hensley TR, Easter AB, Gerdts SE, De Rosa SC, Heit A, McElrath MJ, Andersen-Nissen E. Enumeration of major peripheral blood leukocyte populations for multicenter clinical trials using a whole blood phenotyping assay. J Vis Exp. 2012 Sep 16;(67):e4302. doi: 10.3791/4302. — View Citation

Knudson KM, Hicks KC, Alter S, Schlom J, Gameiro SR. Mechanisms involved in IL-15 superagonist enhancement of anti-PD-L1 therapy. J Immunother Cancer. 2019 Mar 21;7(1):82. doi: 10.1186/s40425-019-0551-y. — View Citation

Lenz HJ. Management and preparedness for infusion and hypersensitivity reactions. Oncologist. 2007 May;12(5):601-9. doi: 10.1634/theoncologist.12-5-601. — View Citation

Mier JW, Brandon EP, Libby P, Janicka MW, Aronson FR. Activated endothelial cells resist lymphokine-activated killer cell-mediated injury. Possible role of induced cytokines in limiting capillary leak during IL-2 therapy. J Immunol. 1989 Oct 1;143(7):2407-14. — View Citation

Raedler LA. Opdivo (Nivolumab): Second PD-1 Inhibitor Receives FDA Approval for Unresectable or Metastatic Melanoma. Am Health Drug Benefits. 2015 Mar;8(Spec Feature):180-3. No abstract available. — View Citation

Rhode PR, Egan JO, Xu W, Hong H, Webb GM, Chen X, Liu B, Zhu X, Wen J, You L, Kong L, Edwards AC, Han K, Shi S, Alter S, Sacha JB, Jeng EK, Cai W, Wong HC. Comparison of the Superagonist Complex, ALT-803, to IL15 as Cancer Immunotherapeutics in Animal Models. Cancer Immunol Res. 2016 Jan;4(1):49-60. doi: 10.1158/2326-6066.CIR-15-0093-T. Epub 2015 Oct 28. — View Citation

Rosenberg SA. IL-2: the first effective immunotherapy for human cancer. J Immunol. 2014 Jun 15;192(12):5451-8. doi: 10.4049/jimmunol.1490019. — View Citation

Salmaninejad A, Valilou SF, Shabgah AG, Aslani S, Alimardani M, Pasdar A, Sahebkar A. PD-1/PD-L1 pathway: Basic biology and role in cancer immunotherapy. J Cell Physiol. 2019 Aug;234(10):16824-16837. doi: 10.1002/jcp.28358. Epub 2019 Feb 19. — View Citation

Sim GC, Radvanyi L. The IL-2 cytokine family in cancer immunotherapy. Cytokine Growth Factor Rev. 2014 Aug;25(4):377-90. doi: 10.1016/j.cytogfr.2014.07.018. Epub 2014 Aug 1. — View Citation

Waldmann TA. The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat Rev Immunol. 2006 Aug;6(8):595-601. doi: 10.1038/nri1901. — View Citation

West EE, Jin HT, Rasheed AU, Penaloza-Macmaster P, Ha SJ, Tan WG, Youngblood B, Freeman GJ, Smith KA, Ahmed R. PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells. J Clin Invest. 2013 Jun;123(6):2604-15. doi: 10.1172/JCI67008. Epub 2013 May 15. — View Citation

Wrangle JM, Velcheti V, Patel MR, Garrett-Mayer E, Hill EG, Ravenel JG, Miller JS, Farhad M, Anderton K, Lindsey K, Taffaro-Neskey M, Sherman C, Suriano S, Swiderska-Syn M, Sion A, Harris J, Edwards AR, Rytlewski JA, Sanders CM, Yusko EC, Robinson MD, Krieg C, Redmond WL, Egan JO, Rhode PR, Jeng EK, Rock AD, Wong HC, Rubinstein MP. ALT-803, an IL-15 superagonist, in combination with nivolumab in patients with metastatic non-small cell lung cancer: a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2018 May;19(5):694-704. doi: 10.1016/S1470-2045(18)30148-7. Epub 2018 Apr 5. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of adverse events (AEs) and SAE	To assess the safety and tolerability of BJ-001 as a single agent administered s.c. at escalating dose levels in adults with solid tumors.	90 days after the last dose
Primary	Severity of AEs in patients with solid tumors enrolled in the study.	To assess the safety and tolerability of s.c. BJ-001 administered at escalating dose levels in combination with Pembrolizumab inhibitor. in adults with solid tumors.	From Day 1 of treatment up to 30 days after last dose
Primary	Dose limiting toxicities (DLTs) BJ-001 as a single agent	To determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of BJ-001 as a single agent.	at the end of week 4 after first dose
Primary	Dose limiting toxicities (DLTs) BJ-001 in combination with pembrolizumab inhibitor.	To determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of s.c. BJ-001 administered at escalating dose levels in combination with pembrolizumab in adults with solid tumors.	at the end of week 4 after first dose
Secondary	Immunogenicity of BJ-001 as a single agent and in combination with Pembrolizumab.	The frequency of anti-drug antibodies (ADA) against BJ-001 as a single agent and in combination with Pembrolizumab.	90 days after last dose
Secondary	Pharmacokinetic (PK) AUC0-t samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.	PK parameters (AUC0-t) following the first dose and the fourth dose	24 weeks
Secondary	Pharmacokinetic (PK) Cmax samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.	PK parameters (Cmax) following the first dose and the fourth dose	24 weeks
Secondary	Pharmacokinetic (PK) Ctrough samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.	PK parameters (Ctrough) following the first dose and the fourth dose	24 weeks
Secondary	Pharmacokinetic (PK) Tmax samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.	PK parameters (Tmax) following the first dose and the fourth dose	24 weeks

External Links

•   KEYTRUDA (pembrolizumab), [package insert]. Merck Sharp & Dohme Corp. Whitehouse Station, NJ.2014. Accessed at Drugs@FDA: FDA Approved Drug Products on December 28, 2018.
•   OPDIVO (nivolumab), [package insert]. Bristol-Myers Squibb Company, Princeton, NJ. 2014. Accessed at Drugs@FDA: FDA Approved Drug Products on November 15, 2018.
•   TECENTRIQ (atezolizumab), [package insert]. Genentech, Inc. San Francisco, CA. 2016. Accessed at Drugs@FDA: FDA Approved Drug Products on December 6, 2018.
•   YERVOY (ipilimumab), [package insert]. Bristol-Myers Squibb Company, Princeton, NJ. 2011. Accessed at Drugs@FDA: FDA Approved Drug Products on July 10, 2018.