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

NCT ID: NCT04186637

Last Updated: 2023-06-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-02
• Study Completion Date: 2023-02-28

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose escalation and expansion

ALPN-202

Group Type: EXPERIMENTAL

ALPN-202

Intervention Type: DRUG

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

Interventions

ALPN-202

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adult 18 to 75 years old at screening

2. Pathologically-confirmed, locally advanced or metastatic unresectable solid tumor of an acceptable histology

Part A (Dose Escalation)

1. that is refractory or resistant to standard therapy, including checkpoint inhibitor(s) if approved

2. or for which standard or curative therapy is not available

Part B (Dose Expansion)

1. metastatic cutaneous melanoma

2. PD-L1-positive cancers (other than cutaneous melanoma or renal cell carcinoma)

3. metastatic renal cell carcinoma

3. Protocol-defined measurable disease

4. Available tumor biopsy representative of current disease

5. ECOG performance status grade 0-2

6. Life expectancy of ≥ 3 months

7. 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)

8. Adequate baseline hematologic, renal, and hepatic function

Exclusion Criteria

1. History of ≥ Grade 3 immune-related adverse event leading to treatment discontinuation

2. Active or prior pneumonitis or interstitial lung disease

3. Presence of any active central nervous system metastases

4. Prior organ allograft or allogeneic hematopoietic stem cell transplantation

5. 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.

6. Receipt of any protocol-restricted therapy within the timeframes indicated:

1. PD-L1 inhibitors: 5 half-lives (e.g., atezolizumab, 135 days; avelumab, 31 days; durvalumab, 85 days)

2. Chemotherapy, small molecule anticancer agents (e.g., kinase inhibitors), or radiation: 2 weeks

3. Other monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, antibody like drugs, cytokines, cell therapies, or radioimmunoconjugates: 4 weeks

7. Any active, known, or suspected autoimmune disease

8. Systemic treatment with corticosteroids (> 10 mg/day prednisone) or other immunosuppressive medication

9. Any second malignancy active within the previous 3 years

10. Active infection requiring therapy at the time of the first dose of ALPN-202.

11. Known seropositivity for or active infection by human immunodeficiency virus, hepatitis B or C.

12. Known allergies, hypersensitivity, or intolerance to ALPN-202 or excipients in the drug product formulation.

13. History of Grade 4 infusion-related, anaphylactic or allergic reaction to any previous Fc-based protein therapy.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alpine Immune Sciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Allison Naumovski, Ph.D.

Role: STUDY_DIRECTOR

Alpine Immune Sciences, Inc.

Locations

Investigational Site (004)

Scottsdale, Arizona, United States

Investigational Site (003)

New Haven, Connecticut, United States

Investigational Site (007)

Lafayette, Indiana, United States

Investigational Site (006)

Louisville, Kentucky, United States

Investigational Site (001)

Grand Rapids, Michigan, United States

Investigational Site (009)

Portland, Oregon, United States

Investigational Site (008)

Pittsburgh, Pennsylvania, United States

Investigational Site (102)

Perth, Nedlands, Australia

Investigational Site (101)

Melbourne, Victoria, Australia

Investigational Site (103)

Melbourne, Victoria, Australia

Countries

United States; Australia

References

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.

Reference Type: DERIVED

PMID: 39097413 (View on PubMed)

Other Identifiers

AIS-B01

Identifier Type: -

Identifier Source: org_study_id