Advanced Cancer, Advanced Solid Tumor, Cervical Cancer, Colon Cancer, Endometrial Cancer, Lung Cancer, Ovarian Cancer
Conditions
Keywords
Antibody-Drug Conjugate, Carcinoma, Cancer, Solid Tumor
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.
Interventions
DRUGPHN-010
PHN-010 is an ADC
Sponsors
Pheon Therapeutics
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose limiting toxicities (Phase 1a) | 18 months |
| Type, incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (Phase 1a) | 18 months |
| Frequency of dose interruptions, reductions, and discontinuations (Phase 1a and 1b) | 18 months |
| Overall response rate (ORR) (Phase 1b) | 36 months |
Secondary
| Measure | Time frame |
|---|---|
| Best overall response (BOR) (Phase 1a and 1b) | 36 months |
| Disease control rate (DCR) (Phase 1a and 1b) | 36 months |
| Progression free survival (PFS) (Phase 1a and 1b) | 36 months |
| Time to response (TTR) (Phase 1a and 1b) | 36 months |
| Overall survival (OS) (Phase 1a and 1b) | 36 months |
| Cancer antigen 125 (CA-125) response (Phase 1a and 1b) | 36 months |
| Time to CA-125 response (Phase 1a and 1b) | 36 months |
| Pharmacokinetics, maximum concentration (Cmax) of total ADC (Phase 1a and 1b) | 36 months |
| Pharmacokinetics, Cmax of total antibody (Phase 1a and 1b) | 36 months |
| Pharmacokinetics, Cmax of free payload (Phase 1a and 1b) | 36 months |
| Pharmacokinetics, time of Cmax (Tmax) of total ADC (Phase 1a and 1b) | 36 months |
| Pharmacokinetics, Tmax of total antibody (Phase 1a and 1b) | 36 months |
| Pharmacokinetics, Tmax of free payload (Phase 1a and 1b) | 36 months |
| Pharmacokinetics, area under the curve (AUC) of total ADC (Phase 1a and 1b) | 36 months |
| Pharmacokinetics, AUC of total antibody (Phase 1a and 1b) | 36 months |
| Pharmacokinetics, AUC of total free payload (Phase 1a and 1b) | 36 months |
| Pharmacokinetics, terminal half-life (t1/2) of total ADC (Phase 1a and 1b) | 36 months |
| Pharmacokinetics, t1/2 of total antibody (Phase 1a and 1b) | 36 months |
| Pharmacokinetics, t1/2 of free payload (Phase 1a and 1b) | 36 months |
| Concentration of anti-drug antibodies (Phase 1a and 1b) | 36 months |
| Type, incidence and severity of AEs and SAEs (Phase 1b) | 18 months |
Countries
United States
Outcome results
None listed