A Study to Investigate Safety and Tolerability of TransCon IL-2 β/γ Alone or in Combination With Pembrolizumab and/or TransCon TLR7/8 Agonist or Other Anticancer Therapies in Adult Participants With Locally Advanced or Metastatic Solid Tumor Malignancies

Study Purpose

TransCon IL-2 β/γ is an investigational drug being developed for treatment of locally advanced or metastatic solid tumors. This is a first-in-human, open-label, Phase 1/2, dose escalation and dose expansion study of TransCon IL-2 β/γ as monotherapy or in combination therapy in adult participants with advanced or metastatic solid tumors. Given the unique PK profile enabled by the TransCon technology, TransCon IL-2 β/γ presents the opportunity to enhance the therapeutic index of current IL-2 therapy.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Key

Inclusion Criteria:

- At least 18 years of age, or country defined local legal age.

- Demonstrated adequate organ function at screening.

- Life expectancy >12 weeks as determined by the Investigator.

- Female and male participants of childbearing potential who are sexually active must agree to use highly effective methods of contraception.

- Participants must have histologically confirmed locally advanced, recurrent, or metastatic solid tumor malignancies that cannot be treated with curative intent (surgery or radiotherapy), with the exception of the neoadjuvant cohorts.

- Part 1 and Part 2: Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.

- Part 3 and Part 4: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

- Participants who have undergone treatment with anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte-associated protein (CTLA-4) antibody must have a washout of at least 4 weeks from the last dose and evidence of disease progression per investigator assessment before Cycle 1 Day 1 (C1D1) with the exception of the neoadjuvant cohorts.

- Participants who have previously received an immunotherapy prior to C1D1 must have any immune-related toxicities resolved to ≤Grade 1 or baseline (prior to the immunotherapy) to be eligible, with the exception of participants on well controlled physiologic endocrine replacement.

- Part 3: Neoadjuvant cohorts: participants must have completely resectable disease.

Key

Exclusion Criteria:

- Symptomatic central nervous system metastases and/or carcinomatous meningitis.

- Active autoimmune diseases, regardless of need for immunosuppressive treatment, with the exception of participants well controlled on physiologic endocrine replacement.

- Any uncontrolled bacterial, fungal, viral, or other infection.

- Significant cardiac disease.

- A marked clinically significant baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >480 ms) [CTCAE Grade 1]) using Fridericia's QT correction formula.

- Positive for human immunodeficiency virus (HIV) or has known active hepatitis B or C infection.

- Known hypersensitivity to any study treatment(s) used in the specific study part/cohort.

- Participants who have been previously treated with IL-2 or IL-2 variants (all participants) - Systemic immunosuppressive treatment with the exception for patients on corticosteroid taper (for example, for chronic obstructive pulmonary disease exacerbation).

- Vaccination with live, attenuated vaccines within 4 weeks of C1D1.

- Treatment with any other anti-cancer systemic treatment (approved or investigational) or radiation therapy within 4 weeks of C1D1.

- Part 3: Other active malignancies within the last 2 years.

- Women who are breastfeeding or have a positive serum pregnancy test during screening

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05081609
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Ascendis Pharma Oncology Division A/S
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Davis Torrejon-Castro
Principal Investigator Affiliation	Medical Monitor
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Australia, Belgium, Canada, Italy, Korea, Republic of, Poland, Singapore, Spain, Taiwan, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Advanced Solid Tumor, Locally Advanced Solid Tumor, Metastatic Solid Tumor, Platinum-resistant Ovarian Cancer, Post Anti-PD-1 Melanoma, 2L+ Cervical Cancer, Neoadjuvant Melanoma, Neoadjuvant Non-Small Cell Lung Cancer, Post Anti-PD-(L)1 Non-Small Cell Lung Cancer, Post Anti-PD-(L)1 Small Cell Lung Cancer, Third Line or Later (3L+) HER2+ Breast Cancer, Second or Third Line (2L/3L) Cervical Cancer, Third-line or Later (3L+) Platinum-resistant Ovarian Cancer (PROC)

Additional Details

IL-2 is a key cytokine that directs the immune system through pleiotropic effects mediated by promoting expansion of both cytotoxic effector cells and Tregs. TransCon IL-2 β/γ is designed as a long-acting delivery prodrug of IL-2 β/γ, a potent cytokine signaling molecule, with the potential to improve the safety and efficacy of IL-2.

Arms & Interventions

Arms

Experimental: Part 1 Monotherapy Dose Escalation: TransCon IL-2 β/γ

TransCon IL-2 β/γ in escalating doses to evaluate safety/tolerability and to determine the MTD and RP2D

Experimental: Part 2 Combination Dose Escalation: TransCon IL-2 β/γ with Pembrolizumab

TransCon IL-2 β/γ with Pembrolizumab in escalating doses to evaluate safety/tolerability and determine the MTD and RP2D

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with SOC Chemo

TransCon IL-2 β/γ using the RP2D with SOC Chemotherapy to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with TransCon TLR7/8 Agonist

TransCon IL-2 β/γ with TransCon TLR7/8 Agonist using the RP2D to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Monotherapy Dose Expansion: TransCon IL-2 β/γ followed by surgery

(Optional Arm): TransCon IL-2 β/γ using the RP2D followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with Pembrolizumab followed by surgery

TransCon IL-2 β/γ using the RP2D with Pembrolizumab followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion:TransCon IL-2 β/γ with TransCon TLR7/8 Agonist followed by surgery

TransCon IL-2 β/γ with TransCon TLR7/8 Agonist using the RP2D followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion:TransCon IL-2 β/γ + Pembrolizumab + SOC Chemo followed by surgery

TransCon IL-2 β/γ using the RP2D with Pembrolizumab and SOC Chemotherapy followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion

TransCon IL-2 β/γ + Pembrolizumab TransCon IL-2 β/γ using the RP2D with Pembrolizumab

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ monotherapy

TransCon IL-2 β/γ monotherapy

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ + trastuzumab

TransCon IL-2 β/γ + trastuzumab

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ + trastuzumab emtansine (T-DM1)

TransCon IL-2 β/γ + trastuzumab emtansine (T-DM1)

Experimental: Part 4 Combination Dose Optimization

TransCon IL-2 β/γ + Pembrolizumab TransCon IL-2 β/γ using the RP2D in titrating doses and/or different dose frequencies with Pembrolizumab

Interventions

Drug: - TransCon IL-2 β/γ

TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion

Drug: - Pembrolizumab

Pembrolizumab will be administered as an intravenous (IV) infusion

Drug: - Chemotherapy drug

SOC chemotherapy will be administered as an intravenous (IV) infusion

Drug: - TransCon TLR7/8 Agonist

TransCon TLR7/8 Agonist will be administered as an IT (Intratumoral) injection

Procedure: - Surgery

Surgery will take place 4-6 weeks after last dose of study treatment.

Drug: - Trastuzumab

Trastuzumab will be administered as an intravenous (IV) infusion

Drug: - Trastuzumab emtansine (T-DM1)

Trastuzumab emtansine (T-DM1) will be administered as an intravenous (IV) infusion

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Ascendis Pharma Investigational Site, Los Angeles, California

Status

Recruiting

Address

Ascendis Pharma Investigational Site

Los Angeles, California, 90048

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