Clinical trial NCT06457997: A Study of PHN-010 in Patients With Advanced Solid Tumors
Official title: First-in-Human, Phase 1b Study of PHN-010, an Antibody Drug Conjugate, in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Lung Cancer
Colon Cancer
Endometrial Cancer
Ovarian Cancer
Cervical Cancer
Advanced Solid Tumor
Advanced Cancer
Keywords: Antibody-Drug Conjugate
Carcinoma
Cancer
Solid Tumor
Lead sponsor: Pheon Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-06-13
Enrollment: 273
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This first-in-human study will evaluate safety, tolerability, anti-tumor activity, immunogenicity, pharmacokinetics and pharmacodynamics of PHN-010, a novel antibody-drug conjugate (ADC), in patients with advanced solid tumors.


Eligibility criteria: Key Inclusion Criteria:

* Has histologically confirmed, advanced/metastatic:

  1. Colorectal adenocarcinoma (CRC), or
  2. Serous, endometroid, or clear-cell epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, or
  3. Serous, endometroid or clear-cell endometrial cancer, or
  4. Adenocarcinoma or squamous-cell carcinoma of the cervix, or
  5. Non-small cell lung cancer (NSCLC).
* Has received at least one prior systemic therapy and radiologically or clinically determined progressive disease during or after the most recent line of therapy, and for whom no further standard therapy is available or who is intolerant to standard therapy.
* Has measurable disease.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Has adequate organ function.
* Has available tumor tissue sample at screening (either an archival specimen collected ≤ 3 years prior to the date of informed consent or fresh biopsy material).

Exclusion Criteria:

* Had prior treatment with any ADC containing topoisomerase-1 inhibiting payload.
* Has unstable central nervous system metastasis.
* Has persistent toxicities from previous systemic anti-cancer treatments of Grade \>1.
* Has received systemic anti-neoplastic therapy within five half-lives or 21 days, whichever is shorter, prior to first dose of the study drug.
* Has received wide-field radiotherapy (\> 30% of marrow-bearing bones) within 28 days, or focal radiation for analgesic purpose or for lytic lesions at risk of fracture within 14 days prior to first dose of the study drug, or no recovery from side effects of such intervention.
* Had major surgery (not including placement of vascular access device or tumor biopsies) within 28 days prior to first dose of the study drug, or no recovery from side effects of such intervention.
* Has acute and/or clinically significant bacterial, fungal, or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV).
* Has a history of non-infectious pneumonitis (NIP) / interstitial lung disease (ILD) requiring systemic steroids, active NIP / ILD or suspected NIP / ILD which cannot be ruled out by imaging for Screening.

Other protocol defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Incidence of dose limiting toxicities (Phase 1a)
timeFrame: 18 months
measure: Type, incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (Phase 1a)
timeFrame: 18 months
measure: Frequency of dose interruptions, reductions, and discontinuations (Phase 1a and 1b)
timeFrame: 18 months
measure: Overall response rate (ORR) (Phase 1b)
timeFrame: 36 months
Secondary outcomes:
measure: Best overall response (BOR) (Phase 1a and 1b)
timeFrame: 36 months
measure: Disease control rate (DCR) (Phase 1a and 1b)
timeFrame: 36 months
measure: Progression free survival (PFS) (Phase 1a and 1b)
timeFrame: 36 months
measure: Time to response (TTR) (Phase 1a and 1b)
timeFrame: 36 months
measure: Overall survival (OS) (Phase 1a and 1b)
timeFrame: 36 months
measure: Cancer antigen 125 (CA-125) response (Phase 1a and 1b)
timeFrame: 36 months
measure: Time to CA-125 response (Phase 1a and 1b)
timeFrame: 36 months
measure: Pharmacokinetics, maximum concentration (Cmax) of total ADC (Phase 1a and 1b)
timeFrame: 36 months
measure: Pharmacokinetics, Cmax of total antibody (Phase 1a and 1b)
timeFrame: 36 months
measure: Pharmacokinetics, Cmax of free payload (Phase 1a and 1b)
timeFrame: 36 months
measure: Pharmacokinetics, time of Cmax (Tmax) of total ADC (Phase 1a and 1b)
timeFrame: 36 months
measure: Pharmacokinetics, Tmax of total antibody (Phase 1a and 1b)
timeFrame: 36 months
measure: Pharmacokinetics, Tmax of free payload (Phase 1a and 1b)
timeFrame: 36 months
measure: Pharmacokinetics, area under the curve (AUC) of total ADC (Phase 1a and 1b)
timeFrame: 36 months
measure: Pharmacokinetics, AUC of total antibody (Phase 1a and 1b)
timeFrame: 36 months
measure: Pharmacokinetics, AUC of total free payload (Phase 1a and 1b)
timeFrame: 36 months
measure: Pharmacokinetics, terminal half-life (t1/2) of total ADC (Phase 1a and 1b)
timeFrame: 36 months
measure: Pharmacokinetics, t1/2 of total antibody (Phase 1a and 1b)
timeFrame: 36 months
measure: Pharmacokinetics, t1/2 of free payload (Phase 1a and 1b)
timeFrame: 36 months
measure: Concentration of anti-drug antibodies (Phase 1a and 1b)
timeFrame: 36 months
measure: Type, incidence and severity of AEs and SAEs (Phase 1b)
timeFrame: 18 months
Other outcomes:
Locations:
city: Orlando
country: United States
facility: AdventHealth
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT - San Antonio
state: Texas
city: Fairfax
country: United States
facility: NEXT - Virginia
state: Virginia
city: Seattle
country: United States
facility: University of Washington/Fred Hutchinson Cancer Center
state: Washington
Study officials:
References: