First-in-Human Study of XMT-1592 in Patients With Ovarian Cancer and NSCLC Likely to Express NaPi2b

NCT04396340 | Terminated Phase 1 FDA Drug

• 1 other identifier: XMT-1592-1
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 1b, a study in high grade serous ovarian cancer and nonsmall cell lung cancer to evaluate the safety and clinical activity of the antibody-drug conjugate (ADC) XMT-1592.

Conditions

Ovarian Cancer; Nonsmall Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose or recommended Phase 2 dose

  Evaluate adverse events and use of concomitant medication use after XMT-1592 doses

  Up to 36 weeks, from the date of first dose until unacceptable side effects or a dose-limiting toxicity is me

Secondary Outcomes (5)

• Time of maximum observed concentration of XMT-1592

  Daily for one week after first dose; weekly until 21 days after first dose; immediately before and after and 1 week after all subsequent doses

• Maximum concentration of XMT-1592

  Daily for one week after first dose; weekly until 21 days after first dose; immediately before and after and 1 week after all subsequent doses

• Area under the concentration curve of the last measurable concentration of XMT-1592

  Daily for one week after first dose; weekly until 21 days after first dose; immediately before and after and 1 week after all subsequent doses

• Antineoplastic effects of XMT-1592

  Every 6 weeks for up to 36 weeks

• Anti-drug antibody and neutralizing antibody

  Every 3 weeks for 9 weeks then every 6 weeks for upto 36 weeks

Study Arms (2)

Dose Escalation

EXPERIMENTAL

XMT-1592 is administered in groups of patients who will receive doses that increase over time until the maximum tolerated dose is achieved.

Biological: XMT-1592

Confirmation of Dose

EXPERIMENTAL

New groups of patients will receive XMT-1592 at the maximum tolerated dose to confirm the recommended Phase 2 dose

Biological: XMT-1592

Interventions

XMT-1592 BIOLOGICAL

XMT-1592 will be administered once every 21 or 28 days until disease progression, unacceptable toxicity, or either the patient or study physician determines it is in the best interest of the patient to discontinue participation in the study.

Confirmation of Dose; Dose Escalation

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to give informed consent.
• ECOG performance status 0 or 1.
• Measurable disease as per RECIST, version 1.1. Resolution of all acute toxic effects of prior therapy or surgical procedures to Grade ≤1 (except alopecia).
• Adequate organ function.
• Confirmed availability of tumor tissue blocks or freshly cut tissue slides for NaPi2b testing. -In EXP, ability to undergo a fresh biopsy before enrollment, unless not medically feasible.
• For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective form of hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner, and to continue the use of contraception for the duration of study treatment and for at least 6 months after the last dose of study treatment.
• Histologically or cytologically confirmed solid tumors of the types specified below, with incurable, locally advanced or metastatic disease that has failed standard therapy or for which no standard treatment option exists.
• Ovarian Cancer: Histological diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer, excluding the mucinous subtype.
• NSCLC: Histological diagnosis of nonsquamous NSCLC.

You may not qualify if:

• Major surgery within 28 days of starting study treatment; -or- systemic anti-cancer therapy within the lesser of 28 days or 5 half-lives of the prior therapy before starting study treatment -or- recent radiation therapy with unresolved toxicity.
• Brain metastases that are: untreated, progressive, have required any type of major treatment, e.g., whole-brain radiation treatment, adjuvant chemotherapy, gamma knife, to control symptoms from brain metastases within 30 days of the first study treatment. Or any history of leptomeningeal metastasis.
• Current known active infection with HIV, hepatitis B virus, or hepatitis C virus.
• No prior history of liver disease such as liver cirrhosis, hepatic fibrosis
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could interfere with per-protocol evaluations.
• Severe dyspnea at rest due to complications of advanced malignancy, or requiring supplementary oxygen therapy.
• Currently active pneumonitis or interstitial lung disease.
• Pregnant or nursing women.
• History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
• Participation in the DES component of the study.
• Prior use of mirvetuximab soravtansine or another ADC containing an auristatin or maytansinoid payload.

Sponsors & Collaborators

• Mersana Therapeutics: lead
• IQVIA Biotech: collaborator

Study Sites (1)

Mary Crowley Cancer Research Center

Dallas, Texas, 75201, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; 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; Endocrine System Diseases; Gonadal Disorders; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Robert Burger, MD

  Mersana Therapeutics

  STUDY DIRECTOR

Study Design

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

Model Details: Open-label, dose escalation to reach MTD. The MTD will be confirmed in 2 parallel cohorts: (1) patients with platinum-resistant ovarian cancer; (2) patients with non-squamous NSCLC, adenocarcinoma subtype.

Study Record Dates

• First Submitted: May 15, 2020
• First Posted: May 20, 2020
• Study Start: May 11, 2020
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)