A total of 18 pts were enrolled in three dose cohorts: gedatolisib 110 mg weekly cofetuzumab pelidotin 1.40 mg/kg every 3 weeks (n=4), 180 mg, 1.40 mg/kg (n=3), and 180 mg, 2.80 mg/kg (n=11). Nausea, anorexia, fatigue, and mucositis were common but rarely reached grade 3 severity. Myelosuppression was uncommon. ORR was 16.67% (3/18). An additional 3 pts had stable disease (of these 2 had stable disease for>18 weeks); CB18 was 27.80%. Median PFS was 2.00 months (95% confidence interval for PFS: 1.20-6.20). Pts with clinical benefit were enriched with genomic alterations in the PI3K and PTK7 pathways.

The most common, treatment-related adverse events for PF-06647020 administered every 3 weeks were nausea, alopecia,fatigue, headache, neutropenia, and vomiting (45%); 25% of patients had grade 3 neutropenia. Two patients experienced doselimiting toxicities (grade 3 headache and fatigue) at the highest every 3 weeks dose evaluated. The recommended phase II dose was 2.80 mg/kg every 3 weeks. The overall safety profile observed with PF-06647020 administered every 2 weeks was similar to that of the every 3 weeks regimen. Systemic exposure for the ADC and total antibody generally increased in a dose-proportional manner. Antitumor activity was observed in treated patients with overall objective response rates of 27.00% in ovarian cancer (n=63), 19% in NSCLC (n=31), and 21% in TNBC (n=29).

Inclusion criteria for Q3W: advanced/metastatic solid tumors refractory to standard therapy, ECOG PS 0-1, adequate organ function; Part 2 targeted ovarian cancer (OVCA), TNBC, and NSCLC. Q2W included platinum-resistant OVCA (≤2 prior lines) or recurrent NSCLC (≤3 prior lines), ECOG PS 0-2. Exclusions: non-epithelial OVCA, active CNS metastases, unresolved bowel obstruction, recent anticancer therapy (4 weeks), or active infections. Both regimens excluded patients with significant comorbidities (uncontrolled infections, recent major surgery/radiation).

This section details safety assessments for PF-06647020 across Q3W (every 3 weeks) and Q2W (every 2 weeks) regimens, monitoring dose-limiting toxicities (DLTs) during initial treatment cycles (21 days for Q3W, 28 days for Q2W) including hematologic (Grade 4 neutropenia, febrile neutropenia), hepatic (Grade ≥3 bilirubin/transaminases), and non-hematologic toxicities. Treatment-emergent adverse events (AEs), graded per NCI CTCAE v4.03, were tracked for up to 32 months (Q3W) or 19 months (Q2W), with lab abnormalities (hematology, chemistry, urinalysis, coagulation) analyzed for shifts from baseline to Grade ≥3.

Pharmacokinetic (PK) parameters (AUCtau, Cmax, CL, Vss, t1/2, Rac, Tmax, AUClast, AUCinf) were evaluated for PF-06647020, its metabolites (PF-06380101, hu6M024 mAb), and dose-normalized values in DDI sub-studies under Q3W (504-hour tau) and Q2W (336-hour tau) regimens. Efficacy endpoints included objective response rate (ORR), duration of response (DOR), disease control rate (DCR), time to progression (TTP), and progression-free survival (PFS), assessed per RECIST v1.1 via tumor imaging every 6-8 weeks. Immunogenicity (anti-drug antibodies [ADA]/neutralizing antibodies [NAb]) was monitored for ~31 months (Q3W) or 18 months (Q2W).

Inclusion criteria require histologically confirmed PTK7-expressing NSCLC, progression after platinum-based therapy +/- targeted agents (≤2 prior lines [≤3 if targeted]), ECOG 0-1, measurable disease, and adequate organ function. Exclusions include active CNS metastases (unless treated/asymptomatic for ≥2 weeks), unresolved Grade ≥2 toxicity (except alopecia/anaemia), significant comorbidities, recent anticancer therapy (within 28 days, except palliative RT ≤10 fractions), or herbal therapies within 7 days.