Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Part A: AsiDNA as a single agent:

The study will follow a dose escalation "3 + 3" cohort design (with 6 dose levels).

All patients will receive a loading dose of AsiDNA for 3 consecutive days as iv infusion at Day 1 (D1), Day 2 (D2) and Day 3 (D3), followed by iv infusion once a week (at D8 and D15 of a 21 days treatment period (1 cycle = 21 days). Each subsequent cycle will be administered on a weekly basis (D1, D8, D15) of a 21 days treatment period.

Part B: AsiDNA combination with Carboplatin with or without Paclitaxel (Background treatments):

* Part B1: Combination cohort of AsiDNA at DL3 (600mg) with Carboplatin AUC 5.
* Part B2: Combination cohort of AsiDNA at DL3 (600mg) with Carboplatin AUC 5 and weekly Paclitaxel: 80 mg/m2 (full dose).

All patients will receive a loading dose of AsiDNA iv infusion (D1, D2, D3) followed by weekly iv administrations.

At cycle 1: Part B1: Carboplatin will be administered by a 1 hour IV infusion at D8, 1 hour after the end of AsiDNA infusion. Part B2: Carboplatin will be administered by a 1 hour IV infusion at D8, 1 hour after the end of AsiDNA infusion and Paclitaxel will be administered by a 1 hour IV infusion at D8, D15, D22 or 1 hour after the end of AsiDNA infusion for weekly administrations.

At each other cycle: AsiDNA will be administered on a weekly basis. Part B1: Carboplatin will be administered by a 1 hour IV infusion at D1, 1 hour after the end of AsiDNA infusion. Part B2; Carboplatin will be administered by a 1 hour IV infusion at D1, 1 hour after the end of AsiDNA infusion and Paclitaxel will be administered on a weekly basis by a 1 hour IV infusion.

Patients will continue study treatment until disease progression, unacceptable toxicity or patient's refusal to continue.

AsiDNA

The aim of the study is to assess:

* Part A: the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of AsiDNA in patients with advanced solid tumors.
* Part B: the safety and preliminary efficacy of AsiDNA in combination with Carboplatin with or without Paclitaxel in patients with Advanced solid tumors.

AsiDNA (a DNA Repair Inhibitor) Administered IntraVenously in Advanced Solid Tumors

An Open-label, Dose-escalation Phase I/Ib Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of AsiDNA, a DNA Repair Inhibitor Administered Intravenously, as Single Agent and to Assess the Safety and the Efficacy of AsiDNA in Combination With Carboplatin With or Without Paclitaxel, in Patients With Advanced Solid Tumors

DLTs will be based on the toxicities observed during the first 3 weeks of study treatment (i.e, cycle 1: from Day 1 to Day 21) for Part A and during the 4 weeks of study treatment (i.e, cycle 1: from Day 1 to Day 28) for Part B.

MTD is defined as the dose immediately below the unacceptable dose or defined as the highest tested dose if no DLT observed at this dose.

Adverse Events will be reported and graded based on the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events (AE) \[CTCAE\] scale, version 4.03.

The following standard plasma PK parameter for IV AsiDNA will be analyzed:

elimination half-life (t1/2) in hours

12-lead ECG will be performed before each cycle (e.g at Day 1 of cycle 1; Day 1 of cycle 2 and Day 1 of each subsequent cycles if any) per usual center's practice.

The following standard plasma PK parameter for IV AsiDNA will be analyzed:

peak plasma concentration (Cmax) in ng/mL

The following standard plasma PK parameter for IV AsiDNA will be analyzed:

time to peak plasma concentration (tmax) in hours

The following standard plasma PK parameter for IV AsiDNA will be analyzed:

area under the curve (AUC) in mg\*h/L.

The following standard plasma PK parameter for IV AsiDNA will be analyzed:

accumulation factor between Day 1 and Day 3 based on total plasma exposure.

Valerio Therapeutics

Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Patients will receive the IMP which is the AsiDNA (etidaligide). AsiDNA will be administered intravenously as a 1-hour infusion. All patients will receive a loading dose for three consecutive days, with Day 1 being the start day of radiotherapy, followed by once weekly administrations during 11 weeks.

The infusion of AsiDNA should be administered between 4 and 6 hours before the planned start of radiotherapy.

After the administration of AsiDNA, Patients with DIBG will receive a total dose of 18 Gy, delivered in 10 fractions of 1.8 Gy, i.e. 5 fractions per week for 2 weeks, starting on Day 1. Patients with supratentorial non-DMG or DMG will receive a total dose of 36 Gy, delivered in 20 fractions of 1.8 Gy, i.e. 5 fractions per week for 4 weeks, starting on Day 1.

Patients with DIBG will receive a total dose of 18 Gy, delivered in 10 fractions of 1.8 Gy, i.e. 5 fractions per week for 2 weeks, starting on Day 1. Patients with supratentorial non-DMG or DMG will receive a total dose of 36 Gy, delivered in 20 fractions of 1.8 Gy, i.e. 5 fractions per week for 4 weeks, starting on Day 1.

Administration of AsiDNA followed by radiotherapy

HGG comprises diffuse midline gliomas (DMG), including diffuse infiltrating brainstem glioma (DIPG), characterised by histone gene mutations, as well as non-DM HGGs mainly in non-midline supratentorial areas, with distinct molecular abnormalities. First-line treatment comprises surgery when doable (non-DM HGGs), and radiotherapy in all cases. Chemotherapy or other drugs in clinical trials may be added during and/or after radiotherapy depending on the HGG subtype. The recurrence rate is nevertheless high in all paediatric and adolescent HGGs. If the time interval between the end of first-line radiotherapy and relapse is long enough, re-irradiation often provides good palliation of symptoms, delays disease progression, improves quality of life and has minimal and manageable toxicity. Nevertheless, strategies to increase efficacy without increasing toxicity in the treatment of recurrent paediatric HGG are much needed.

AsiDNA™ is a DNA repair inhibitor that increases the vulnerability of tumour cells to irradiation without increasing toxicity in healthy tissues. Its novel mechanism of action, based on perturbation of the DNA damage recognition steps in DNA repair, makes its activity specific to tumour cells. Intravenous administration of AsiDNA is currently being investigated in adults with advanced solid tumours. The MTD was not reached during the escalating dose study on the safety, pharmacokinetics and pharmacodynamics of AsiDNA administered as a 1-hour infusion, however an optimal dose range (400-600 mg) was identified for further development, based on the favourable safety and PK profiles. Preclinical studies on AsiDNA added to radiotherapy have shown increased survival and no increase in short- or long-term toxicity due to the high doses of irradiation.

The study will provide paediatric patients who have recurrent HGG with early access to innovation, even during the early drug development stage in adults.

AsiDNA Children, Adolescents and Young Adults

A Phase Ib/II Study on AsiDNA in Association With Re-irradiation in Children, Adolescents and Young Adults With High-grade Glioma

Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.

Dose-limiting toxicities, i.e. grade ≥ 3 toxicities according to NCI-CTCAE version 5.0, considered as at least possibly related to the treatment during the 8 weeks after treatment initiation.

3-month progression-free survival (PFS), i.e. the probability for a patient to be alive and free of disease progression based on clinical or radiological criteria, or death from any cause at 3 months after inclusion in the study. Radiological progression will be assessed using RAPNOHGG criteria. Patients lost to follow-up will be counted as failures at the last assessment date.

Late-onset toxicity, defined as any toxicity, i.e. any AE considered as at least possibly related to treatment, that occurs more than 8 weeks after treatment initiation;

MR pattern of disease response and of potential treatment-related toxicity, assessed by central review based on morphological and functional imaging features present on the various MR examinations;

Best objective response rate, defined as the percentage of patients with complete or partial responses according to RAPNO criteria as assessed by the investigator

Overall survival, defined as the time from inclusion in the study to death from any cause.

Patients alive or lost to follow-up at the cut-off date will be censored at the last date they were known to be alive;

Palliation of symptoms, assessed using the Lansky Play Scale (LPS) or Karnofsky score of ≥ 50 %

Need for corticosteroids and/or bevacizumab

Maximal observed drug concentration (Cmax);

absorption and elimination half-life (t1/2))

time to reach maximum observed drug concentration (Tmax);

area under the curve (AUC0-t (experimental time points)

Institut Curie

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Breast Neoplasms

Prostatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Disease Attributes

Urogenital Neoplasms

Genital Diseases

Urogenital Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Three dose levels of AsiDNA delivered intravenously weekly in combination with Olaparib

Recommended Phase 2 dose of AsiDNA delivered intravenously weekly in combination with Olaparib

All patients will receive a loading dose of AsiDNA intravenously (D1, D2, D3) followed by weekly intravenous administrations in combination with Olaparib.

Olaparib is given orally in combination with AsiDNA

Ashish Gulati, M.D.

Kari Cortez

This is a phase 1b/2 open-label, multicenter, basket study to determine the safety, anti-tumor activity, tolerability, and pharmacokinetics /pharmacodynamics of AsiDNA in combination with olaparib in participants with recurrent epithelial ovarian cancer, breast cancer and metastatic castration-resistant prostate cancer who have progressed on previous Poly (ADP-ribose) polymerase (PARP) inhibitor therapy. The study will be conducted in two phases. The Phase 1b dose escalation study designed to establish the safety, tolerability, pharmacologically active doses/ maximum tolerated dose and/or recommended phase 2 dose of AsiDNA in combination with olaparib.

This is a phase 1b/2 open-label, multicenter, basket study to determine the safety, anti-tumor activity, tolerability, and pharmacokinetics /pharmacodynamics of AsiDNA in combination with olaparib in participants with recurrent epithelial ovarian cancer, breast cancer and metastatic castration-resistant prostate cancer who have progressed on previous PARP inhibitor therapy. The study will be conducted in two phases. The Phase 1b dose escalation study designed to establish the safety, tolerability, pharmacologically active doses/ maximum tolerated dose and/or recommended phase 2 dose of AsiDNA in combination with olaparib.

Once the RP2D has been determined the Phase 2 study will proceed evaluating AsiDNA in combination with olaparib in participants with recurrent ovarian cancer, recurrent breast cancer and recurrent CRPC that failed or progressed on PARP inhibitors (PARPi) therapy. The objective of Phase 2 study is to evaluate the preliminary efficacy as measured by ORR of AsiDNA in combination with olaparib in each of the three cohorts. Eligible participants will be included to receive AsiDNA by IV infusion in addition to olaparib.

Dose Escalation followed by dose expansion

Study To Assess Safety And Efficacy Of AsiDNA In Combination With Olaparib In Participants With Recurrent Solid Tumors

A Phase 1b/2 Basket Study To Assess The Safety And Efficacy Of AsiDNA™ In Combination With Olaparib In Participants With Recurrent Solid Tumors

• Dose-limiting toxicities (DLTs) as determined by adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE 5.0)

• Dose-limiting toxicities (DLTs) as determined by physical examination

• Dose-limiting toxicities (DLTs) as determined vital signs

• Dose-limiting toxicities (DLTs) as determined by ECG

• Dose-limiting toxicities (DLTs) as determined by clinical laboratory tests

• Dose-limiting toxicities (DLTs) as determined by Eastern Cooperative Oncology Group (ECOG) performance status

Pharmacologically active dose (PAD) and/or Maximum Tolerated Dose (MTD).

Objective Response Rate (ORR) defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on Investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria guidelines.

• Safety PK parameters: total exposure including Area under the plasma concentration-time curve (AUC)0-24.

• Safety PK parameters: total exposure including AUC0-last.

• Safety PK parameters: total exposure including Cmax.

• Duration of Response: time from earliest date of disease response (CR or PR) until earliest date of disease progression, or death, whichever occurs first.

• Disease Control Rate: the proportion of participants in whom a CR or PR or stable disease is observed as best overall response.

• Progression Free Survival: time from start of treatment until the first documented radiographic progressive disease or death, whichever occurs first.

Immune System Diseases

Hypersensitivity

Niraparib

Rucaparib

Part A: AsiDN in addition to Niraparib (Safety evaluation) Part B: AsiDN in addition to Niraparib (Efficacy evaluation and Safety confirmation )

Unit dose: Vial containing 100 mg of AsiDNA™ (free acid) Regimen: 3 consecutive infusions (D1, D2, D3) followed by a once a week iv infusion on D8 and D15 of a 21 day-treatment cycle at first cycle, then weekly iv infusion in the absence of disease progression or unacceptable toxicity Mode/route: 1 hour intravenous (iv) infusion

Unit dose: Hard capsule containing 100mg of Niraparib Regimen: The last dose given during the 6 previous months of Niraparib 200 mg/day or 300 mg/day, (or 100 mg/day only if the patient has received this dose since at least 6 months) Daily, 1, 2 or 3 hard capsules at 100mg once daily at approximately the same time each day.

Mode/route: Per os

Product name: Olaparib Pharmaceutical form: Tablets containing 100 or 150mg of Olaparib Route of administration: per os Dose Regimen: The last dose given during the 6 previous months of Olaparib 600 mg/day or 500 mg/day, (or 400 mg/day only if the patient has received this dose since at least 6 months) Two times daily (300mg or 250 mg or 200mg) at approximately the same time each day.

Product name: Rucaparib Pharmaceutical form: Tablets containing 200 or 250 or 300mg of Rucaparib Route of administration: per os Dose Regimen: The last dose given during the 6 previous months of Rucaparib 1200 mg/day or 1000 mg/day, or 800mg/day (or 600 mg/day only if the patient has received this dose since at least 6 months) Two times daily (600mg or 500mg or 400mg or 300mg) at approximately the same time each day.

Patricia PAUTIER, MD

Thibaud MOTREFF

The objective of REVOCAN study is to assess the abrogation of PARP inhibitors resistance in patients with relapsed platinum sensitive ovarian cancer treated with PARP inhibitors in maintenance since at least 6 months and who have only an increase of CA 125 without any progression according to RECIST criteria. AsiDNATM at 600 mg will be tested in addition to PARP inhibitors given according to the label in REVOCAN study.

Safety and Efficacy of AsiDNATM, a DNA Repair Inhibitor, Administered Intravenously in Addition to PARP Inhibitors in Patients With Relapsed Platinum Sensitive Ovarian Cancer Already Treated With PARP Inhibitors Since at Least 6 Months

An Open-label, Multicentric, Phase Ib/II Study to Assess the Safety and Efficacy of AsiDNATM, a DNA Repair Inhibitor, Administered Intravenously in Addition to Niraparib in Patients With Relapsed Platinum Sensitive Ovarian Cancer Already Treated With Niraparib Since at Least 6 Months

Occurrence of cases of Dose Limiting Toxicity (DLT) will be recorded and reviewed according to a predefined definition.

DLTs include the following specific treatment-related AEs occurring during the first 21 days (from D1 to D21) treatment period (based on the National Cancer

Institute \[NCI\] Common Terminology Criteria for Adverse Events (AE) \[CTCAE\] scale, version 5.0 defined as:

* Haematological toxicity:

  1. Grade 4 neutropenia lasting ≥ 7 days,
  2. Febrile Neutropenia,
  3. Grade 4 thrombocytopenia or grade 3 thrombocytopenia associated with bleeding.
* Non haematological toxicity:

Any drug-related non-hematological toxicity grade ≥ 3 toxicity (except alopecia, fatigue, nausea, controlled hypertension and vomiting adequately treated with antiemetic treatment and non-clinically significant laboratory values abnormalities).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
AsiDNA (a DNA Repair Inhibitor) Administered IntraVenously in Advanced Solid Tumors	NCT03579628	Advanced Cancer	AsiDNA	18 Years -	Valerio Therapeutics
AsiDNA Children, Adolescents and Young Adults	NCT05394558	Recurrent High-...	AsiDNA	12 Months - 24 Years	Institut Curie
Study To Assess Safety And Efficacy Of AsiDNA In Combination With Olaparib In Participants With Recurrent Solid Tumors	NCT05700669	Metastatic Cast... Recurrent Epith... Breast Cancer	AsiDNA Olaparib	18 Years -	Valerio Therapeutics
Safety and Efficacy of AsiDNATM, a DNA Repair Inhibitor, Administered Intravenously in Addition to PARP Inhibitors in Patients With Relapsed Platinum Sensitive Ovarian Cancer Already Treated With PARP Inhibitors Since at Least 6 Months	NCT04826198	Ovarian Cancer	AsiDNA Niraparib Olaparib Rucaparib	18 Years -	Gustave Roussy, Cancer Campus, Grand Paris
Study To Assess Safety And Efficacy Of AsiDNA In Combination With Olaparib In Participants With Recurrent Solid Tumors	NCT05700669	Metastatic Cast... Recurrent Epith... Breast Cancer	AsiDNA Olaparib	18 Years -	Valerio Therapeutics
AsiDNA Children, Adolescents and Young Adults	NCT05394558	Recurrent High-...	AsiDNA	12 Months - 24 Years	Institut Curie
AsiDNA (a DNA Repair Inhibitor) Administered IntraVenously in Advanced Solid Tumors	NCT03579628	Advanced Cancer	AsiDNA	18 Years -	Valerio Therapeutics

Spots Global Cancer Trial Database for asidna

Every month we try and update this database with for asidna cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for asidna

Every month we try and update this database with for asidna cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for asidna cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.