An Open-label Study of ALPN-202 in Subjects With Advanced Malignancies

NCT04186637 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: AIS-B01
• Study Type: interventional
• Target: 62
• Locations: 2 countries
• Sites: 10

Brief Summary

This is a cohort-based, open-label dose escalation and expansion study in adults with advanced solid tumors or lymphoma, refractory or resistant to standard therapy, or without available standard or curative therapy.

Conditions

Advanced Solid Tumor; Lymphoma

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  Type, incidence, and severity of adverse events as assessed by CTCAE

  Up to 30 days after last dose of study drug

Secondary Outcomes (1)

• Objective response

  Up to 30 days after last dose of study drug

Study Arms (1)

Dose escalation and expansion

EXPERIMENTAL

ALPN-202

Drug: ALPN-202

Interventions

ALPN-202 DRUG

Multiple dose levels and dose regimens of ALPN-202 will be administered

Dose escalation and expansion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult 18 to 75 years old at screening
• Pathologically-confirmed, locally advanced or metastatic unresectable solid tumor of an acceptable histology
• Part A (Dose Escalation)
• that is refractory or resistant to standard therapy, including checkpoint inhibitor(s) if approved
• or for which standard or curative therapy is not available
• Part B (Dose Expansion)
• metastatic cutaneous melanoma
• PD-L1-positive cancers (other than cutaneous melanoma or renal cell carcinoma)
• metastatic renal cell carcinoma
• Protocol-defined measurable disease
• Available tumor biopsy representative of current disease
• ECOG performance status grade 0-2
• 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, and hepatic function

You may not qualify if:

• History of ≥ Grade 3 immune-related adverse event leading to treatment discontinuation
• 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 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:
• PD-L1 inhibitors: 5 half-lives (e.g., atezolizumab, 135 days; avelumab, 31 days; durvalumab, 85 days)
• 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.
• Known allergies, hypersensitivity, or intolerance to ALPN-202 or excipients in the drug product formulation.

Sponsors & Collaborators

• Alpine Immune Sciences, Inc.: lead

Study Sites (10)

Investigational Site (004)

Scottsdale, Arizona, 85258, United States

Location

Investigational Site (003)

New Haven, Connecticut, 06520, United States

Location

Investigational Site (007)

Lafayette, Indiana, 47905, United States

Location

Investigational Site (006)

Louisville, Kentucky, 40202, United States

Location

Investigational Site (001)

Grand Rapids, Michigan, 49546, United States

Location

Investigational Site (009)

Portland, Oregon, 97213, United States

Location

Investigational Site (008)

Pittsburgh, Pennsylvania, 15232, United States

Location

Investigational Site (102)

Perth, Nedlands, 6009, Australia

Location

Investigational Site (101)

Melbourne, Victoria, 3004, Australia

Location

Investigational Site (103)

Melbourne, Victoria, 3004, Australia

Location

Related Publications (1)

• 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

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, Inc.

  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: November 27, 2019
• First Posted: December 5, 2019
• Study Start: June 2, 2020
• Primary Completion: November 9, 2022
• Study Completion: February 28, 2023
• Last Updated: June 5, 2023

Record last verified: 2023-06

Locations

US (7); AU (3)