FDA Clears Phase 1/2a Trial of Novel PD-1/VEGFR2 Antibody in Solid Tumors

The FDA has cleared an investigational new drug (IND) application for OTP-01, an investigational PD-1 and VEGFR2 antibody, as a treatment for patients with solid tumors as part of a phase 1/2a trial (NCT07266428), according to a press release from the developer, Ottimo Pharma.¹

Investigators of the open-label trial will assess the safety, tolerability, pharmacodynamics, pharmacokinetics, and early activity of the novel agent among patients in the US and Australia at approximately 20 centers across the world. Investigators have already administered a dose of OTP-01 to the first patient; recruitment for the trial is ongoing. Additionally, developers are exclusively manufacturing the investigational therapy in the US.

“I am proud of our Ottimo team for their remarkable speed in bringing OTP-01 into the clinic since coming out of stealth,” David Epstein, chair and chief executive officer at Ottimo Pharma, stated in the press release.¹ “We are developing this unique, first-in-class antibody to be the ideal backbone therapy to combine with antibody drug conjugates or chemotherapy, with the aim of creating a new standard of care across a wide range of solid tumors.”

Developers engineered OTP-01 as an IgG1 monoclonal antibody that simultaneously engages the PD-1 immune checkpoint and the VEGFR2 angiogenic pathway. According to preclinical data, the agent may inhibit PD-1 in combination with allosteric inhibition of VEGFR2 while modulating several immune subsets and optimally promoting tumor vascular normalization. The agent’s dual-targeting design may facilitate distribution based on the tumor microenvironment and boost intratumoral immune activation.

In the phase 1/2a study, an estimated population of 170 patients will receive OTP-01 intravenously at no more than once a week, with subsequent blood tests conducted to assess the agent’s safety and drug levels.² Additionally, investigators will perform radiographic scans of patient tumors at baseline as well as regular intervals during the study, and patients will have the option to undergo a tumor biopsy before and after therapy to help determine how OTP-01 impacts cancer and the immune system.

The trial’s primary end points include the frequency and severity of adverse effects (AEs) and serious AEs, progression-free survival, disease control rate, duration of response, and objective response rate. Secondary end points include the plasma concentrations of OTP-01, the maximum plasma concentration, the minimum plasma concentration, and the agent’s half-life.

Patients 18 years and older with histologically or cytologically confirmed incurable, recurrent, or metastatic solid tumors; measurable disease based on RECIST v1.1 guidelines; adequate hematologic, renal, and hepatic function; and an ECOG performance status of 0 or 1 are eligible for enrollment on the trial. Other eligibility criteria include having a minimum life expectancy of 3 months and the resolution of all toxicities associated with prior cancer therapies to grade 1 or lower per NCI CTCAE v5.0 guidelines.

Those with a history of grade 4 allergic or anaphylactic reactions to prior monoclonal antibodies or prior toxicity requiring permanent discontinuation of previous immunotherapy are ineligible for enrollment on the trial. Patients are also unable to enroll if they have active autoimmune disease requiring systemic therapy within 2 years of study entry or definitive radiotherapy within 6 weeks or palliative radiation within 2 weeks prior to initiating study treatment.

“Our aim is to fully assess the potential of this distinctive antibody by generating comprehensive clinical and translational data to inform both dose selection and combination strategies, and to ​set the stage for broad development across multiple tumor types,” Mehdi Shahidi, MD, head of Development and chief medical officer at Ottimo, concluded.¹

References

1. Ottimo Pharma announces FDA clearance of investigational new drug (IND) application for OTP-01, a first-in-class, dual-paratopic, single-agent, anti-PD-1/VEGFR2 antibody. News release. Ottimo Pharma. January 8, 2026. Accessed January 8, 2026. https://tinyurl.com/4d3yvsep
2. A study of OTP-01, a dual paratopic PD-1/​VEGFR2 antibody, in patients with advanced solid tumors. ClinicalTrials.gov. Updated December 23, 2025. Accessed January 8, 2025. https://tinyurl.com/4e5rpdpu