IRB Study Number 25-018
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives
• To compare antitumor activity in ORR per Response Evaluation Criteria in Solid Tumor (RECIST) Guidelines version (v) 1.1 as assessed by blinded independent central review (BICR) in patients with incurable metastatic / recurrent HNSCC patients progressed on after anti-PD-1 and platinum containing therapy, treated with petosemtamab monotherapy vs investigator’s choice monotherapy
• To compare OS in patients with incurable metastatic / recurrent HNSCC progressed on after anti-PD-1 and platinum-containing therapy, treated with petosemtamab monotherapy vs investigator’s choice monotherapy
Secondary Objectives
• To evaluate antitumor activity in ORR per RECIST v1.1 as assessed by investigator review
• To evaluate antitumor activity in DOR per RECIST v1.1 as assessed by BICR and investigator review
• To evaluate antitumor activity in TTR per RECIST v1.1 as assessed by BICR and investigator review
• To evaluate antitumor activity in PFS per RECIST v1.1 as assessed by BICR and by investigator review
• To evaluate antitumor activity in CBR per RECIST v1.1 as assessed by BICR and by investigator review
• To evaluate safety and tolerability of petosemtamab monotherapy
• To evaluate patient health-related quality of life (HRQL) using the European Organisation for Research and Treatment of Cancer (EORTC) validated Quality of Life of Cancer Patients Questionnaire (QLQ-C30)
• To evaluate patient HRQL using the updated EORTC validated Quality of Life of Head and Neck Cancer Patients Questionnaire (QLQ-H&N43)
• To characterize the PK of petosemtamab
• To characterize the population PK of petosemtamab
• To characterize the immunogenicity of petosemtamab
Inclusion Criteria
Signed ICF before initiation of any study procedures
Age ≥ 18 years at signing of ICF
Histologically previously confirmed HNSCC with evidence of metastatic or locally advanced disease not amenable to standard therapy with curative intent.
HNSCC patients progressed on or after anti-PD-1 therapy and platinum-containing therapy. Patients treated with platinum-containing therapy only in the adjuvant setting, or in the context of multimodal therapy for locally advanced disease, should have disease progression within 6 months of the last dose of platinum-containing therapy. Patients should not have received >1 line of chemotherapy in the incurable metastatic/recurrent setting.
The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
Documentation of p16 status (positive or negative) by local laboratory IHC for patients with primary oropharyngeal cancer must be available before further clinical assessment to determine eligibility. If local p16 status is not available, then an archival tumor specimen from primary or early metastatic disease should be provided for central testing.
Previous treatments with anti-EGFR therapies are not allowed, unless cetuximab was used with radiotherapy as a multimodal treatment of local disease and the recurrence/progression of the disease was ≥1 year from the last dose of cetuximab.
A baseline new tumor sample (formalin-fixed paraffin-embedded [FFPE]) from a metastatic or recurrent primary site. If the patient has an available tumor sample as an FFPE block with sufficient material (block containing material for ≥20 slides with >20% tumor content), and has not received further anticancer treatment since sample collection, then a new tumor biopsy at baseline is not necessary. If there is no sample, or ≤20 slides are available, then the Sponsor should be consulted to confirm eligibility. If taking a new biopsy is unsafe, and an archival block (taken before previous lines of treatment) is available, then the Sponsor should also be consulted to confirm eligibility. (NOTE: When enough tissue samples for exploratory analyses have been collected, then tissue collection for exploratory analyses will be discontinued.)
Measurable disease as defined by RECIST v1.1 by radiologic methods
ECOG PS of 0 or 1
Life expectancy ≥ 12 weeks, as per investigator
Adequate organ function:
• Absolute neutrophil count (ANC) ≥1.5 X 109/L
• Hemoglobin ≥9 g/dL
• Platelets ≥100 x 109/L
• Serum magnesium, sodium, corrected total calcium, phosphate, and potassium within normal ranges (or corrected with supplements or appropriate treatment If these electrolyte ranges are not within normal range despite corrective treatment, then the Sponsor should be consulted to confirm eligibility.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN) and total bilirubin ≤1.5 x ULN (unless due to known Gilbert’s syndrome, who are excluded if total bilirubin >3.0 x ULN or direct bilirubin >1.5 x ULN); in cases of liver involvement, ALT/AST ≤5 x ULN and total bilirubin ≤2 x ULN will be allowed, unless due to known Gilbert’s syndrome when total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN will be allowed.
• Serum creatinine ≤1.5 x ULN or creatinine clearance ≥60 mL/min calculated according to the Cockroft and Gault formula or Modification of Diet in Renal Disease (MDRD) formula for patients aged >65 years.
• Serum albumin ≥3 g/dL.
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 x ULN unless patient is receiving anticoagulant therapy and in therapeutic range of intended used anticoagulant.
• Activated partial thromboplastin time (APTT) or partial thromboplastin time (PTT)≤1.5 x ULN unless patient is receiving anticoagulant therapy and is in therapeutic range of intended used anticoagulant
Known human immunodeficiency Virus (HIV)-positive patients are eligible provided the cluster of differentiation 4 (CD4+)count is ≥300/μL, viral load is undetectable, and the patient is currently receiving highly active antiretroviral therapy (HAART).
Judged appropriate by the investigator to receive investigator’s choice monotherapy, if randomized to that treatment arm.
Exclusion Criteria
Central nervous system metastases that are untreated or symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 14 days of study entry.
Known leptomeningeal involvement
Participation in an interventional clinical study with any investigational drug within 4 weeks prior to study entry, OR participation in any clinical study with petosemtamab, at any time prior to study entry, regardless if petosemtamab was received or not
Any systemic anticancer therapy within 4 weeks of the first dose of study treatment.
Major surgery or radiotherapy within 3 weeks of the first dose of study treatment. Patients who received prior radiotherapy to ≥25% of bone marrow are not eligible, irrespective of when it was received.
Persistent Grade >1 clinically significant toxicities related to prior antineoplastic therapies (except for alopecia); stable sensory neuropathy Grade ≤2 National Cancer Institute–Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 is allowed.
History of hypersensitivity reaction to any of the excipients of petosemtamab or any investigator’s choice monotherapy treatment required for this study.
Unstable angina; history of congestive heart failure of Class II-IV New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (except atrial fibrillation, paroxysmal supraventricular tachycardia); or history of myocardial infarction within 6 months of study entry
History of prior malignancies with the exception of excised cervical intraepithelial neoplasia or nonmelanoma skin cancer, or curatively treated cancer deemed at low risk for recurrence with no evidence of disease for ≥3 years, or a second primary malignancy for which inclusion of patient should be discussed with the Sponsor
Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy, including patients with a history of interstitial lung disease (ILD) (eg, pneumonitis or pulmonary fibrosis), or evidence of ILD on baseline chest computerized tomography (CT) scan
Current serious illness or medical conditions including, but not limited to, uncontrolled active infection, clinically significant pulmonary, metabolic or psychiatric disorders
Patients with known infectious diseases:
• Active hepatitis B infection (hepatitis B surface antigen [HBsAg] positive) without receiving antiviral treatment. Note:
o Patients who are HBsAg positive must receive antiviral treatment with lamivudine, tenofovir, entecavir, or other antiviral agents, starting ≥7 days before the initiation of study treatment.
o Patients with antecedents of hepatitis B (ie, anti-HBc positive, HBsAg and hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] negative) are eligible.
• Positive test for hepatitis C virus (HCV) RNA. Note: Patients in whom HCV infection resolved spontaneously (ie, positive HCV antibodies without detectable HCV RNA) or who achieved a sustained response after antiviral treatment and show absence of detectable HCV RNA ≥6 months (with the use of interferon [IFN]-free regimens) or ≥ 12 months (with the use of IFN-based regimens) after cessation of antiviral treatment are eligible.
Pregnant or breastfeeding patients; patients of childbearing potential must use highly effective contraception methods prior to study entry, for the duration of study participation, and for 6 months after the last dose of petosemtamab.
Patient has a primary tumor site of nasopharynx, or sinonasal (any histology).
