A Clinical Study to Evaluate the Safety, Tolerability and Efficacy of IOS-1002 Administered Alone and in Combination With Pembrolizumab, a PD-1 Monoclonal Antibody in Advanced Solid Tumors

NCT05763004 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: IOS-1002-201KEYNOTE-F49 / MK-3475-F49
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 5

Brief Summary

The goal of this clinical trial is to learn about IOS-1002 in patients with solid tumors. The main questions it aims to answer are:

• To determine the safety and tolerability of various doses of IOS-1002 administered alone and/or in combination with KEYTRUDA® (pembrolizumab) in a single dose escalation scheme
• To determine the safety, tolerability and efficacy of a selected dose of IOS-1002 administered every 2 weeks alone and in combination with a PD-1 Antibody The study will be conducted in 3 parts:
• Part A (Phase 1a, monotherapy and combination therapy dose escalation): IOS-1002 alone and IOS-1002 plus PD-1 mAb in patients with advanced solid tumors
• Part B (Phase 1b, monotherapy cohort expansion): IOS-1002 alone in patients with advanced solid tumors
• Part C (Phase 1b, combination therapy cohort expansion): IOS-1002 plus PD-1 mAb in patients with advanced solid tumors.

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (1)

• To determine the incidence of treatment emergent Adverse Events (Safety and Tolerability) of various doses of IOS-1002 administered alone and/or in combination with a PD-1 mAb in subjects with advanced solid tumors

  Incidence of any Adverse Event DLTs AEs leading to study treatment discontinuationAEs leading to study discontinuation Abnormal laboratory parameters, vital signs, ECOG performance status, ECG results, and physical examination

  From date of randomization until the date of first documented progression (end of study) or date of death from any cause, whichever came first, assessed up to 48 months

Secondary Outcomes (4)

• To investigate the preliminary antitumor activity of IOS-1002 and in combination with a PD-1 mAb

  From date of randomization until the date of first documented progression (end of study) or date of death from any cause, whichever came first, assessed up to 48 months

• To characterize the PK of IOS-1002 alone and in combination with a PD-1 mAb

  From date of randomization until the date of first documented progression (end of study) or date of death from any cause, whichever came first, assessed up to 48 months

• To characterize the immunogenicity of IOS-1002 alone and in combination with a PD-1 mAb

  From date of randomization until the date of first documented progression (end of study) or date of death from any cause, whichever came first, assessed up to 48 months

• To characterize the immunogenicity of IOS-1002

  From date of randomization until the date of first documented progression (end of study) or date of death from any cause, whichever came first, assessed up to 48 months

Study Arms (2)

IOS-1002 Monotherapy

EXPERIMENTAL

Drug: IOS-1002

IOS-1002 Combination Therapy with KEYTRUDA® (pembrolizumab)

EXPERIMENTAL

Drug: IOS-1002 + KEYTRUDA® (pembrolizumab)

Interventions

IOS-1002 DRUG

monotherapy

IOS-1002 Monotherapy

IOS-1002 + KEYTRUDA® (pembrolizumab) DRUG

combination therapy

IOS-1002 Combination Therapy with KEYTRUDA® (pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old at the time of Screening (signing the informed consent form \[ICF\]).
• Histologically or cytologically confirmed advanced solid tumor (metastatic and/or unresectable) with measurable disease per RECIST v1.1:
• Malignancy that has relapsed or is refractory to, at least 1 standard treatment regimen in the advanced or metastatic setting, if such a therapy exists or for which the subjects who refuse or are ineligible for standard therapy.
• Subjects with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enrol provided the lesions have demonstrated clear progression and can be measured accurately.
• For combination therapy dose-escalation: subjects who have undergone treatment with any agent specifically targeting checkpoint pathway inhibition (such as PD-1, PD-L1, PDL-2, LAG-3, or CTLA-4 antibody) for at least 3 months before disease progression and must have a gap of at least 4 weeks from the last treatment before receiving study treatment on Cycle 1 Day 1
• a. Subjects who experienced prior Grade 1 to 2 checkpoint therapy-related immune mediated AEs must have confirmed recovery from these events at the time of study entry, other than endocrinopathies treated with supplementation. Where applicable, these subjects must also have completed steroid tapers for treatment of these AEs by a minimum of 14 days prior to commencing treatment with study therapy. b) Eligibility of subjects with prior Grade ≥3 checkpoint therapy-related immune AEs, will be considered on a case-by-case basis after discussion with the Medical Monitor (eg, asymptomatic isolated Grade 3 lipase elevations without clinical or radiological features of pancreatitis will be permitted to enrol).
• Adequate organ function at Screening
• Willingness to provide consent to allow the acquisition of fresh tumor biopsy and/or existing formalin tissue sample
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

You may not qualify if:

• Subjects with known or suspected CNS metastases, untreated CNS metastases, or with the CNS as the only site of disease are excluded. EXCEPTION: Subjects with controlled brain metastases will be allowed to enroll. Controlled brain metastases are defined as no radiographic progression for at least 4 weeks following radiation and/or surgical treatment (or 4 weeks of observation if no intervention is clinically indicated), and off steroids for at least 4 weeks prior to Screening, and no new or progressive neurological signs and symptoms.
• Subjects with known carcinomatous meningitis.
• Subjects with a prior malignancy except non-melanoma skin cancers, and in situ cancers such as: bladder, colon, cervical/dysplasia, melanoma, or breast. Subjects with other second malignancies diagnosed more than 2 years ago who have received therapy with curative intent with no evidence of disease during the interval who are considered by the Investigator to present a low risk for recurrence will be eligible.
• Subjects with active, known, or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, euthyroid with a history of Grave's disease (subjects with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid-stimulating immunoglobulin prior to first dose of study treatment), psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity, including subjects with pneumonitis.
• Chronic Obstructive Pulmonary Disease (COPD) requiring recurrent steroids bursts or chronic steroids at doses greater than 10 mg/day of prednisone or the equivalent.
• Uncontrolled or significant cardiovascular disease
• Evidence of active infection ≤7 days prior to initiation of study treatment therapy (does not apply to viral infections that are presumed to be associated with the underlying tumor type required for study entry).
• Evidence or history of active or latent tuberculosis infection including purified protein derivative recently converted to positive; chest x-ray with evidence of infectious infiltrate.
• History of any chronic hepatitis
• Known history of testing positive for HIV or known acquired immunodeficiency syndrome. Note: Testing for HIV must be performed at Screening.
• Any anticancer therapy (eg, chemotherapy, biologics, vaccines, or hormonal treatment) including investigational drugs within 4 weeks prior to the first dose of study treatment administration, except for GnRH agonist therapy for subjects with prostate cancer and anticancer therapies with half-life of \<4 weeks eg, prior use of EGFR TKI (completed at least two weeks prior to first dose of study treatment is acceptable).
• Subjects with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration except for adrenal replacement steroid doses \>10 mg daily prednisone equivalent in the absence of active autoimmune disease. Note: Treatment with a short course of steroids (\<5 days) up to 7 days prior to initiating study treatment is permitted.
• Use of non-oncology vaccines containing live virus for prevention of infectious diseases within 12 weeks prior to study treatment. The use of inactivated seasonal influenza vaccines eg, Fluzone® will be permitted on study without restriction.
• Any major surgery within 4 weeks of study treatment administration. Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment.

Sponsors & Collaborators

• ImmunOs Therapeutics AG: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

Monash Health Medical Center

Clayton, Australia

Location

Austin Health / Cancer Clinical Trials Center

Heidelberg, Australia

Location

Alfread Health

Melbourne, Australia

Location

Peter MacCallum Cancer Center

Melbourne, Australia

Location

Linear Clinical Research

Perth, Australia

Location

MeSH Terms

Interventions

pembrolizumab

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2023
• First Posted: March 10, 2023
• Study Start: March 15, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5)