A Phase 1 First-In-Human Study of the Anti-CD73 IPH5301 Alone or in Combination With Chemotherapy and Trastuzumab in Patients With Advanced Solid Tumors

NCT05143970 | Recruiting Phase 1 DMC

• 1 other identifier: CHANCES-IPC 2021-008
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

CHANCES-IPC 2021-008 is First In Human, Phase I, multicenter, European study evaluating an anti-CD73, IPH5301 in advanced and/or metastatic cancer. The trial will be conducted in two parts, Part I- Dose escalation: This part aims to identify the maximum tolerated dose (MTD) of IPH5301 agent in monotherapy and recommended phase 2 dose (RP2D) for future trials, followed by a safety expansion study part cohort. Part II- Expansion cohort: A total of 12 HER2-expressing breast cancer patients is planned to be enrolled into the next expansion cohort to select a recommended dose of IPH5301 to be administered in combination with chemotherapy and trastuzumab for evaluation in future trials with selected advanced solid tumors.

Conditions

Metastatic Cancer; Metastatic Breast Cancer; Metastatic Pancreatic Cancer; Metastatic Gastric Cancer; Metastatic Lung Cancer; Metastatic Ovary Cancer; Oesophageal Cancer; Endometrial Cancer; Advanced Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Occurrence of dose limiting toxicity (DLT) of IPH5301 in monotherapy in the dose escalation and in combination with paclitaxel and trastuzumab in the expansion cohort

  DLTs would include any grade 3 toxicity or higher that occurs during the first 4 weeks from the first injection of IPH5301, with the some exceptions

  1 month

Study Arms (1)

IPH5301 administration

EXPERIMENTAL

Part I- Dose escalation: Escalating dose levels of IPH5301 will be evaluated. Part II-Cohort Expansion: IPH5301 will be administrated in combination with trastuzumab and paclitaxel

Drug: IPH5301 ALONE OR IN COMBINATION WITH CHEMOTHERAPY AND TRASTUZUMAB

Interventions

IPH5301 ALONE OR IN COMBINATION WITH CHEMOTHERAPY AND TRASTUZUMAB DRUG

Part I-Dose escalation Patients will receive IPH5301 alone on day 1 (Week 1). Treatment will be administered every 2 weeks until progression or unacceptable toxicity or other reasons requiring treatment discon-tinuation, for a maximum duration of 12 months. Part II- Expansion cohort Patients will receive IPH5301 at a recommended dose (RP2D) or a next lower dose (RP2D-1)in combination with trastuzumab and paclitaxel, at day 1 and every 2 weeks up to 6 cycles of paclitaxel. The RP2D dose will not exceed the designated maximum tolerated dose (MTD).

IPH5301 administration

Eligibility Criteria

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

You may qualify if:

• Patients with incurable advanced and/or metastatic cancer.
• Patients with any of the following cancers:
• In dose escalation: carcinoma of the breast, stomach, esophagus, pancreas, endometrium, ovary or lung.
• In cohort expansion : carcinoma of the breast that expresses HER2. Eligibility is based on HER2 expression as determined locally. HER2-positive is defined by IHC 3+ or gene amplification by in situ hybridization and HER2-low is defined by IHC 1+ or 2+ and no gene amplification by in situ hybridization.
• Prior treatment with at least one prior systemic therapy in the advanced metastatic setting
• Dose escalation: no limit on number of prior systemic therapies and considered as failing standard therapeutic alternatives and candidate to a phase I study by a multi-disciplinary tumor board.
• Cohort expansion: patients must have previously re-ceived (or be considered as non-eligible to) all authorized standard treatments as described below :
• HER2-positive breast cancer patient must have received prior (or be considered as ineligible to) trastuzumab +/- pertuzumab-based chemotherapy, trastuzumab deruxtecan, and could have received, trastuzumab emtansine, and capecitabine+anti-HER2 (trastuzumab, lapatinib or trastuzumab tucatinib) according to label.
• HER2-low breast cancer patients must be candidate to paclitaxel-based chemotherapy according to standard guidelines (i.e. must have received and demonstrated resistance to prior endocrine therapy in combination with CDK4/6 inhibitor if estrogen receptor (ER) and/or progesterone receptor (PR),-positive breast cancer; must have received trastuzumab deruxtecan if ER and/or PR-positive breast cancer and candidate to second-line chemotherapy or beyond ; must have received previous immune checkpoint inhibitor-based chemotherapy if first line-treated PD-L1-positive triple-negative breast cancer; must have received sacituzumab govitecan if triple-negative breast cancer previously treated by at least 2 regimen of cytotoxic chemotherapy, including one line in the metastatic setting ; must have received PARP inhibitors if germline BRCA mutation; must have demonstrated no disease progression within 12 months of any taxanes-based previous chemotherapy)
• Presence of at least one measurable lesion by RECIST outside of the CNS.
• At least 18 years of age.
• ECOG performance status of ≤1.
• For patients included in cohort expansion, adequate echocar-diogram, with a left ventricular ejection fraction ≥55%. Patients with a history of LVEF decline (\< 50%) on anti-HER2 treatment will not be allowed to participate.
• For patients included in the cohort expansion, feasibility of obtaining tumor biopsy at study entry.
• All non-hematological AEs related to prior therapy must have completely resolved or improved to Grade 1 prior to screening for this study (except for alopecia).

You may not qualify if:

• Prior treatment with other monoclonal antibodies or small mol-ecules targeting CD73 or the adenosine pathway.
• Patients with known spinal cord compression.
• Patients with grade 2 or higher peripheral neuropathy.
• Symptomatic, untreated, or actively progressing central nerv-ous system (CNS) metastases. Patients with suspected CNS involvement at screening should have an magnetic resonance imaging (MRI) (preferred) or computed tomography (CT) each preferably with IV contrast of the brain prior to study entry to rule them out. Asymptomatic patients with treated CNS lesions are eligible, provided that definied criteria are met
• Known allergic reactions attributed to compounds of similar product.
• Patients with dyspnea at rest and history of pneumonit-is/interstitial lung disease.
• Patients with any serious underlying medical condition that would impair the subject from receiving or tolerating the planned treatment.
• Concurrent enrollment in another clinical trial, unless it is an non-interventional clinical study or the follow-up period of an interventional study.
• Any concurrent treatment with any anti-cancer agents or drugs that could have anti-tumor effects.
• Active auto-immune disease within the past 2 years.
• ≥ Grade 3 immune related AE or an immune-related neuro-logic or ocular AE of any grade while receiving prior immunotherapy.
• Subjects who have undergone major surgery \<28 days prior to starting study drug.
• Treatment with any conventional or investigational anticancer therapy within 28 days prior to day 1 of study treatment.
• Receipt of live attenuated vaccine or SARS-CoV-2 vaccine within 30 days prior to the first dose of study drug
• Primary immunodeficiency and/or history of allogenic transplantation.

Sponsors & Collaborators

• Innate Pharma: collaborator
• Institut Paoli-Calmettes: lead

Study Sites (1)

Institut Paoli Calmettes

Marseille, France

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Breast Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Lung Neoplasms; Ovarian Neoplasms; Esophageal Neoplasms; Endometrial Neoplasms

Interventions

Drug Therapy; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders; Head and Neck Neoplasms; Esophageal Diseases; Uterine Neoplasms; Uterine Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Anthony GONCALVES, MD PhD

  Institut Paoli-Calmettes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

DOMINIQUE GENRE

CONTACT

0491223778; drci.up@ipc.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2021
• First Posted: December 3, 2021
• Study Start: January 21, 2022
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)