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

NCT04294576 | Unknown Phase 1 FDA Drug

• 2 other identifiers: BJ-001-01-001USKEYNOTE-F13
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 5

Brief 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

Conditions

Locally Advanced/Metastatic Solid Tumors

Keywords

FIH; Solid Tumors

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (5)

• Immunogenicity of BJ-001 as a single agent and in combination with Pembrolizumab.

  90 days after last dose

• Pharmacokinetic (PK) AUC0-τ samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.

  24 weeks

• Pharmacokinetic (PK) Cmax samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.

  24 weeks

• Pharmacokinetic (PK) Ctrough samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.

  24 weeks

• Pharmacokinetic (PK) Tmax samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.

  24 weeks

Study Arms (2)

Arm 1; BJ-001

EXPERIMENTAL

Phase 1a Part 1, Part 2, and Part 4: dose escalation for BJ-001 as single agent

Drug: BJ-001

Arm 2; BJ-001 and pembrolizumab

EXPERIMENTAL

Phase 1a Part 3 and Part 5: dose escalation for BJ-001 in combination with Pembrolizumab Phase 1b: expansion cohorts for the combination of BJ-001 and pembrolizumab

Drug: BJ-001; Drug: Pembrolizumab

Interventions

BJ-001 DRUG

BJ-001 dosed via SC injection as single agent. One cycle is 6 weeks.

Arm 1; BJ-001; Arm 2; BJ-001 and pembrolizumab

Pembrolizumab DRUG

BJ-001 dosed via SC injection in combination with Pembrolizumab One cycle is 6 weeks.

Also known as: Keytruda

Arm 2; BJ-001 and pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 αVβ3, αVβ5, or αVβ6 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• BJ Bioscience, Inc.: lead
• PPD Development, LP: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Greenville Hospital System University Medical Center (ITOR)

Greenville, South Carolina, 29605, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Northwest Medical Specialities

Tacoma, Washington, 98405, United States

Location

Related 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.

  PMID: 29442540 BACKGROUND

• 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.

  PMID: 30651291 BACKGROUND

• 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.

  PMID: 25403209 BACKGROUND

• 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.

  PMID: 20144472 BACKGROUND

• 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.

  PMID: 27217584 BACKGROUND

• 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.

  PMID: 23007739 BACKGROUND

• 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.

  PMID: 30898149 BACKGROUND

• 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.

  PMID: 31265503 BACKGROUND

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

  PMID: 17522249 BACKGROUND

• 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.

  PMID: 2528594 BACKGROUND

• 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.

  PMID: 26629287 BACKGROUND

• 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.

  PMID: 26511282 BACKGROUND

• 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.

  PMID: 24907378 BACKGROUND

• 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.

  PMID: 25200249 BACKGROUND

• 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.

  PMID: 30784085 BACKGROUND

• 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.

  PMID: 16868550 BACKGROUND

• 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.

  PMID: 23676462 BACKGROUND

• 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.

  PMID: 29628312 BACKGROUND

Related 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.

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Joe Zhang, PhD

  BJ Bioscience

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: no masking is used. All involved know the identity of the intervention assignment.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2020
• First Posted: March 4, 2020
• Study Start: December 4, 2019
• Primary Completion: April 29, 2024
• Study Completion: October 22, 2024
• Last Updated: November 9, 2023

Record last verified: 2023-09

Locations

US (5)