OTP-01 (dual PD-1/VEGFR2 antibody) for advanced solid tumors

Phase 1/2A Study of OTP-01, a Dual Paratopic PD-1/VEGFR2 Antibody, in Patients With Advanced Solid Tumors

This trial tests whether OTP-01, an antibody that targets PD‑1 and VEGFR2, is safe, tolerable, and can shrink tumors in adults with advanced solid tumors.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 170 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ottimo Pharma Limited (industry)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone
• Locations: 9 sites (Boston, Massachusetts and 8 other locations)
• Trial ID: NCT07266428 on ClinicalTrials.gov

What this trial studies

OTP‑01 is a dual paratopic antibody designed to block PD‑1 and inhibit VEGFR2 signaling; the trial enrolls adults with advanced solid tumors to define a recommended dose and to monitor safety, pharmacokinetics, and antitumor activity. The study includes a dose‑escalation phase to identify the recommended phase 2 dose and expansion/backfill cohorts for specific tumor types. Participants receive OTP‑01 by intravenous infusion (no more than once weekly), with frequent early blood draws for safety and drug levels, periodic radiographic scans per RECIST v1.1, and optional pre‑ and on‑treatment biopsies. Investigators record adverse events, drug concentrations, and tumor responses to determine tolerability and preliminary efficacy.

Who should consider this trial

Good fit: Adults with histologically confirmed advanced, unresectable or metastatic solid tumors who have measurable disease and who have progressed on, are intolerant to, or have declined available standard therapies per protocol are the intended participants.

Not a fit: Patients whose cancers are well controlled by approved standard treatments, who have inadequate organ function, active uncontrolled illnesses, or whose tumor types are excluded by the protocol are unlikely to receive benefit from this trial.

Why it matters

Potential benefit: If successful, OTP‑01 could provide a new option that combines immune checkpoint blockade with anti‑angiogenic activity to control tumor growth for patients who have exhausted standard therapies.

How similar studies have performed: Combinations targeting PD‑1 and VEGF/VEGFR pathways have shown benefit in several solid tumors, but a single antibody simultaneously targeting PD‑1 and VEGFR2 is a novel approach with limited prior human data.

Eligibility criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed advanced (incurable, recurrent, unresectable, or metastatic) solid tumors.

   1. For dose escalation cohort patients: patients must have a tumor type as defined in the protocol. Patients will have progression on or after or intolerance to most recent systemic therapy. Patients must have received approved standard therapy that is available to the patient that is known to confer clinical benefit, unless this therapy is contraindicated, intolerable to the patient, or is declined by the patient. The reason for treatment decline must be clearly documented in the medical record.
   2. For backfill cohorts: patients must have a tumor type as defined in the protocol. If patients decline an available standard therapeutic regimen known to confer benefit to enroll on this study, the discussion must be clearly documented in the medical record.
2. Measurable disease per RECIST v1.1. Additionally, patients with breast or ovarian cancer with non-measurable, evaluable disease are eligible.
3. ECOG performance status 0-1.
4. Life expectancy of at least 3 months.
5. Willing to provide a pretreatment tumor sample (either an archival sample or a sample obtained by pretreatment biopsy).
6. All toxicity resulting from prior cancer therapies must have resolved to NCI CTCAE v5.0 ≤ Grade 1 or pre-therapy baseline with the exception of alopecia or ≤ Grade 2 neuropathy.
7. Adequate hematological, renal, and hepatic function.
8. Other protocol-defined inclusion criteria apply.

Exclusion Criteria:

1. Receiving systemic corticosteroids at prednisone-equivalent dose of \> 10 mg/day within 4 weeks prior to signing consent. Chronic systemic corticosteroid therapy for physiologic replacement (≤ 10 mg/day of prednisone equivalents) and the use of non-systemic corticosteroids (e.g., inhaled, topical, intra-nasal, intra-articular, or ophthalmic) are permitted
2. History of Grade 4 allergic or anaphylactic reaction to prior monoclonal antibody therapy or allergic reaction to any excipients within the investigational product
3. History of toxicity requiring permanent discontinuation of prior cancer immunotherapy
4. Have an active autoimmune disease that has required systemic treatment in past 2 years (replacement therapy is not considered a form of systemic treatment)
5. History of organ or stem cell transplant or need for immunosuppressive treatment
6. Have proteinuria \> 2 + (within 7 days prior to initiation of study treatment).
7. Received any chemotherapy, immunotherapy or investigational anticancer therapy within 3 weeks or 5 half-lives (whichever is shorter; minimum of 2 weeks) prior to first dose of study drug
8. Definitive radiotherapy within 6 weeks and palliative radiation within 2 weeks prior to the first dose of study drug. If previously irradiated, lesions must have demonstrated clear-cut progression prior to being eligible for evaluation as target lesions
9. Other protocol and subprotocol-defined exclusion criteria apply

Where this trial is running

Boston, Massachusetts and 8 other locations

• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (RECRUITING)
• South Texas Accelerated Research Therapeutics (START) Midwest — Grand Rapids, Michigan, United States (RECRUITING)
• South Texas Accelerated Research Therapeutics (START) — San Antonio, Texas, United States (RECRUITING)
• START Mountain Region — West Valley City, Utah, United States (RECRUITING)
• Cancer Research SA — Adelaide, Australia (RECRUITING)
• Chris O'Brien Lifehouse — Camperdown, Australia (RECRUITING)
• Linear Clinical Research — Nedlands, Australia (RECRUITING)
• START Dublin Early Phase Clinical Trials Unit — Dublin, Ireland (RECRUITING)
• Auckland City Hospital — Auckland, New Zealand (RECRUITING)

Conditions: Advanced Solid Tumors, advanced solid tumors