ALPN-202 With PD-1 Inhibition in Advanced Malignancies (NEON-2)

• ClinicalTrials.gov Identifier: NCT04920383
• Recruitment Status: Active, not recruiting
• First Posted: June 9, 2021
• Last Update Posted: November 9, 2022
• Sponsor: Alpine Immune Sciences, Inc.
• Information provided by (Responsible Party): Alpine Immune Sciences, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor; Lymphoma	Drug: ALPN-202; Drug: Pembrolizumab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Study of ALPN-202 Combined With PD-1 Inhibition in Subjects With Advanced Malignancies (NEON-2)
• Actual Study Start Date: June 22, 2021
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Escalation and Expansion; ALPN-202 + Pembrolizumab	Drug: ALPN-202; Various doses; Drug: Pembrolizumab; Varies

Outcome Measures

Primary Outcome Measures :

1. Dose-limiting Toxicities (DLTs) [ Time Frame: Up to 6 weeks following study day 1 ]
   Incidence of DLTs
2. Adverse Events (AEs) [ Time Frame: 30 days after last dose of study drug ]
   Type, incidence, severity, and seriousness of AEs
3. Laboratory Abnormalities [ Time Frame: Up to 30 days after last dose of study drug ]
   Type, incidence, and severity of laboratory abnormalities

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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:

  1. that is eligible for treatment with a PD-1 or PD-L1 inhibitor, or
  2. that is refractory or resistant to standard therapy, or
  3. 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

Exclusion Criteria:

• 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:

  1. 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)
  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
• 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.
• History of Grade 4 infusion-related, anaphylactic or allergic reaction to any previous Fc-based protein therapy.

• Any serious or uncontrolled cardiovascular condition, including but not limited to:

  1. Any history of myocarditis of any etiology
  2. History of New York Heart Association Class III or IV congestive heart failure, myocardial infarction, unstable angina, cerebrovascular accident, cardiac hospitalization, or other acute uncontrolled heart disease within 6 months of scheduled C1D1
  3. Left ventricular ejection fraction < 45% on screening echocardiogram
  4. Any clinically significant findings on screening EKG such as atrial or ventricular arrythmia (other than sinus tachycardia) or AV conduction abnormality such as left bundle branch block (such subjects may be enrolled after cardiology clearance and Medical Monitor approval)
• Has received prior radiotherapy within 2 weeks of start of study treatment, or have had a history of radiation pneumonitis

Contacts and Locations

Locations

United States, Georgia

Investigational Site (213)

Atlanta, Georgia, United States, 30322

United States, Massachusetts

Investigational Site (212)

Boston, Massachusetts, United States, 02114

United States, Michigan

Investigational Site (301)

Grand Rapids, Michigan, United States, 49546

United States, Tennessee

Investigational Site (203)

Nashville, Tennessee, United States, 37203

United States, Texas

Investigational Site (215)

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Alpine Immune Sciences, Inc.

More Information

• Responsible Party: Alpine Immune Sciences, Inc.
• ClinicalTrials.gov Identifier: NCT04920383
• Other Study ID Numbers: AIS-B02
• First Posted: June 9, 2021
• Last Update Posted: November 9, 2022
• Last Verified: November 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action