ALPN-202 With PD-1 Inhibition in Advanced Malignancies

NCT04920383 | Terminated Phase 1 FDA Drug

• 2 other identifiers: AIS-B02MK-3475-D05/KEYNOTE-D05
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 5

Brief Summary

This is a cohort-based, open-label dose escalation and expansion study in adults with advanced solid tumors or lymphoma.

Conditions

Advanced Solid Tumor; Lymphoma

Outcome Measures

Primary Outcomes (3)

• Dose-limiting Toxicities (DLTs)

  Incidence of DLTs

  Up to 6 weeks following study day 1

• Adverse Events (AEs)

  Type, incidence, severity, and seriousness of AEs

  30 days after last dose of study drug

• Laboratory Abnormalities

  Type, incidence, and severity of laboratory abnormalities

  Up to 30 days after last dose of study drug

Study Arms (1)

Dose Escalation and Expansion

EXPERIMENTAL

ALPN-202 + pembrolizumab KEYTRUDA®

Drug: ALPN-202; Drug: pembrolizumab KEYTRUDA®

Interventions

ALPN-202 DRUG

Various doses

Dose Escalation and Expansion

pembrolizumab KEYTRUDA® DRUG

Varies

Dose Escalation and Expansion

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult 18 to 80 years old at screening
• Pathologically confirmed, locally advanced or metastatic unresectable solid tumor, or Hodgkin or Non-Hodgkin lymphoma (including transformed lymphoma) of an acceptable histology:
• that is eligible for treatment with a PD-1 or PD-L1 inhibitor, or
• that is refractory or resistant to standard therapy, or
• for which standard or curative therapy is not available.
• Have received ≥ 2 prior systemic anti-cancer therapies (lymphoma subjects only)
• Protocol-defined measurable disease
• Available tumor biopsy representative of current disease
• ECOG performance status grade 0-1
• Life expectancy of ≥ 3 months
• Recovery to Grade ≤ 1 for any non-laboratory toxicity resulting from previous anticancer therapy prior to first dose of ALPN-202 (except alopecia, hearing loss, Grade ≤ 2 neuropathy, or endocrinopathy managed with replacement therapy)
• Adequate baseline hematologic, renal, hepatic and cardiac function

You may not qualify if:

• Any history of ≥ Grade 3 immune-related adverse event (irAE) requiring discontinuation from treatment or any history of a cardiovascular irAE
• Active or prior pneumonitis or interstitial lung disease
• Presence of any active central nervous system metastases
• Prior organ allograft or allogeneic hematopoietic stem cell transplantation
• Any other serious or uncontrolled health condition, which, in the opinion of the Investigator, would place the subject at undue risk from the study, impair the ability of the subject to receive protocol specified therapy, or interfere with the interpretation of study results.
• Receipt of any protocol-restricted therapy within the timeframes indicated:
• Checkpoint inhibitors, including PD-(L)1 (e.g., pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab), CTLA-4 (e.g., ipilimumab, tremelimumab), and Lag-3 (e.g., relatlimab), costimulatory agonists (including but not limited to CD28, CD134 (OX40), CD137 (4-1BB)): 3 months (135 days for atezolizumab)
• Chemotherapy, small molecule anticancer agents (e.g., kinase inhibitors), or radiation: 2 weeks
• Other monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, antibody-like drugs, cytokines, cell therapies, or radioimmunoconjugates: 4 weeks
• Any active, known, or suspected autoimmune disease
• Systemic treatment with corticosteroids (\> 10 mg/day prednisone) or other immunosuppressive medication
• Any second malignancy active within the previous 3 years
• Active infection requiring therapy at the time of the first dose of ALPN-202.
• Known seropositivity for or active infection by human immunodeficiency virus, hepatitis B or C, or or Severe Acute Respiratory Syndrome Coronavirus 2.
• Known allergies, hypersensitivity, or intolerance to ALPN-202 or excipients in the drug product formulation.

Sponsors & Collaborators

• Alpine Immune Sciences, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

Investigational Site (213)

Atlanta, Georgia, 30322, United States

Location

Investigational Site (212)

Boston, Massachusetts, 02114, United States

Location

Investigational Site (301)

Grand Rapids, Michigan, 49546, United States

Location

Investigational Site (203)

Nashville, Tennessee, 37203, United States

Location

Investigational Site (215)

San Antonio, Texas, 78229, United States

Location

Related Publications (2)

• Cavalcante L, Chandana S, Lakhani N, Enstrom A, LeBlanc H, Schmalz J, Lengyel K, Schneider F, Thomas H, Chisamore MJ, Peng SL, Naumovski A, Davar D. Case report of fatal immune-mediated myocarditis following treatment with davoceticept (ALPN-202), a PD-L1-dependent CD28 costimulator and dual PD-L1/CTLA-4 checkpoint inhibitor, in combination with pembrolizumab. J Immunother Cancer. 2024 Aug 13;12(8):e009475. doi: 10.1136/jitc-2024-009475.

  PMID: 39142718 DERIVED

• Davar D, Cavalcante L, Lakhani N, Moser J, Millward M, McKean M, Voskoboynik M, Sanborn RE, Grewal JS, Narayan A, Patnaik A, Gainor JF, Sznol M, Enstrom A, Blanchfield L, LeBlanc H, Thomas H, Chisamore MJ, Peng SL, Naumovski A. Phase I studies of davoceticept (ALPN-202), a PD-L1-dependent CD28 co-stimulator and dual PD-L1/CTLA-4 inhibitor, as monotherapy and in combination with pembrolizumab in advanced solid tumors (NEON-1 and NEON-2). J Immunother Cancer. 2024 Aug 3;12(8):e009474. doi: 10.1136/jitc-2024-009474.

  PMID: 39097413 DERIVED

MeSH Terms

Conditions

Lymphoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Allison Naumovski, Ph.D.

  Alpine Immune Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2021
• First Posted: June 9, 2021
• Study Start: June 22, 2021
• Primary Completion: November 8, 2022
• Study Completion: February 28, 2023
• Last Updated: March 1, 2024

Record last verified: 2024-02

Locations

US (5)