Testing the Combination of Anetumab Ravtansine With Either Nivolumab, Nivolumab and Ipilimumab, or Gemcitabine and Nivolumab in Advanced Pancreatic Cancer
A Phase I Study of Anetumab Ravtansine in Combination With Either Anti-PD-1 Antibody, or Anti-CTLA4 and Anti-PD-1 Antibodies or Anti-PD-1 Antibody and Gemcitabine in Mesothelin-Positive Advanced Pancreatic Adenocarcinoma
4 other identifiers
interventional
74
2 countries
45
Brief Summary
This phase I trial studies the side effects and best dose of anetumab ravtansine when given together with nivolumab, ipilimumab and gemcitabine hydrochloride in treating patients with mesothelin positive pancreatic cancer that has spread to other places in the body (advanced). Anetumab ravtansine is a monoclonal antibody, called anetumab ravtansine, linked to a chemotherapy drug called DM4. Anetumab attaches to mesothelin positive cancer cells in a targeted way and delivers DM4 to kill them. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving anetumab ravtansine together with nivolumab, ipilimumab, and gemcitabine hydrochloride may work better in treating patients with pancreatic cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2019
Longer than P75 for phase_1
45 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 24, 2019
CompletedFirst Posted
Study publicly available on registry
January 25, 2019
CompletedStudy Start
First participant enrolled
December 9, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 31, 2027
May 13, 2026
January 1, 2026
7.2 years
January 24, 2019
May 12, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Maximum tolerated dose (MTD)
This study will follow a 3+3 dose escalation design.
Up to 30-37 days post treatment
Secondary Outcomes (1)
Biomarker analysis
Up to 100 days post treatment
Study Arms (3)
Arm I (anetumab ravtansine, nivolumab)
EXPERIMENTALPatients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Treatment repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood on study.
Arm II (anetumab ravtansine, nivolumab, ipilimumab)
EXPERIMENTALPatients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Patients also receive ipilimumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of cycles 2-4. Treatment repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood on study.
Arm III (anetumab ravtansine, nivolumab, gemcitabine)
EXPERIMENTALPatients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Patients also receive gemcitabine hydrochloride over 30-40 minutes on days 1 and 8. Treatment repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood on study.
Interventions
Undergo biopsy
Undergo collection of blood
Given IV
Given IV
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed pancreatic adenocarcinoma that is metastatic or unresectable or recurrent
- Only subjects with positive mesothelin expression (Ventana mesothelin \[MSLN\]- immunohistochemistry \[IHC\]; Negative=H-score =\< 10) are eligible. This is to be performed centrally. For dose escalation cohorts, patients with mesothelin expression in \>= 5% of tumor cells are eligible. For dose expansion, patients must have moderate or strong tumor mesothelin expression defined as \>= 30% of tumor cells with mesothelin expression of 2+/3 on immunohistochemical staining
- Patients must be \>= 18 years of age
- Patients must have received and either progressed or been intolerant to at least 1 systemic therapy
- Life expectancy of at least 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status score 0-1 (Karnofsky \>= 80%)
- Prior anti-cancer treatments are permitted (i.e. chemotherapy, including gemcitabine and nab-paclitaxel; radiotherapy; hormonal, or immunotherapy with the exception of anti-CTLA4, anti-PD1/PD-L1, and combination of anti-CTLA4 and anti-PD1/PD-L1) providing toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery have either resolved, improved to baseline or G1
- At least one (1) measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per RECIST version (v)1.1; measurable disease is a requirement in both dose escalation phase and dose expansion phase
- Note: Measurable lesions may be in an irradiated field as long as there is documented progression and the lesion(s) can be reproducibly measured
- At least one lesion safely accessible for biopsy unless medically contraindicated; biopsies are mandatory both in dose escalation and in dose expansion; in dose escalation and in expansion the following biopsies are optional: at baseline and at progression; biopsy could be: core needle or excisional or punch biopsy. Irradiated lesions can be biopsied if tumor growth is confirmed
- Patients must have archival tumor tissue for mesothelin expression and correlative biomarker studies; subjects must consent to provide tumor blocks or slides and the availability of the tissue must be confirmed prior to subjects receiving study medication; if an archived tumor specimen is unavailable or unsuitable for correlative biomarker studies, a pre-treatment fresh tumor biopsy is required
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours of study enrollment or randomization; WOCBP must agree to appropriate methods of contraception for the duration of treatment and for 6 months after completion of treatment; males who are sexually active with a partner of childbearing potential must agree to appropriate methods of contraception for the duration of treatment. For all male patients, prior to treatment, advice should be sought for conserving sperm due to the chance of irreversible infertility as a consequence of treatment; genetic consultation is recommended if the patient wishes to have children after ending treatment; the investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control
- Highly effective (failure rate of less than 1% per year) contraception methods include:
- Combined (estrogen and progesterone containing: oral, intravaginal, transdermal) and progesterone-only (oral, injectable, implantable) hormonal contraception associated with inhibition of ovulation
- Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
- +15 more criteria
You may not qualify if:
- Patients not recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment. Concurrent enrollment in a non-interventional clinical study or the follow-up period of an interventional study is allowed.
- Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least six weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 14 days prior to trial treatment
- Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial, anti-viral or anti-fungal therapy (washout: 7 days prior to cycle 1 day 1 \[C1D1\])
- Patients are prohibited from receiving the following therapies during the screening and treatment phase of this trial:
- Antineoplastic systemic chemotherapy or biological therapy
- Radiation therapy
- Note: Radiation therapy to a symptomatic solitary lesion or to the brain may be considered on an exceptional case by case basis after consultation with Cancer Therapy Evaluation Program (CTEP); the patient must have clear measurable disease outside the radiated field; administration of palliative radiation therapy will be considered clinical progression for the purposes of determining progression free survival (PFS)
- Live vaccines within 30 days prior to the first dose of trial treatment and while participating in the trial; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Chalmette-Guerin (BCG), typhoid (oral) vaccine, and intranasal influenza vaccines (e.g., Flu-Mist)
- Current or prior use of systemic immunosuppressive medication (except corticosteroids at physiological doses, not exceeding 10 mg prednisone-equivalent day) within 10 days before the first dose of study medication; intranasal, inhaled, topical, or local steroid injections are allowed; steroids as premedication for hypersensitivity reactions (i.e. CT scan premedication) are allowed; systemic glucocorticoids used to modulate symptoms from an event of suspected immunologic etiology are permitted
- Any major surgery within 4 weeks of study drug administration
- Concomitant second malignancies (except adequately treated squamous cell carcinoma \[SCC\] or basal cell carcinoma \[BCC\] skin cancers or in situ bladder, breast or cervical cancers) within the last 3 years prior to study entry
- Uncontrolled or significant cardiovascular disease, including but not limited to ongoing or active symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, unstable cardiac arrhythmia
- National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5 \>= grade (G)2 peripheral neuropathy (sensory or motor)
- Patients with corneal epitheliopathy and at the discretion of the ophthalmologist any other eye disorder
- Active or prior documented inflammatory bowel disease (i.e. ulcerative colitis)
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (45)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
City of Hope at Irvine Lennar
Irvine, California, 92618, United States
Keck Medicine of USC Koreatown
Los Angeles, California, 90020, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
HaysMed
Hays, Kansas, 67601, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
Lawrence Memorial Hospital
Lawrence, Kansas, 66044, United States
The University of Kansas Cancer Center - Olathe
Olathe, Kansas, 66061, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211, United States
Mercy Hospital Pittsburg
Pittsburg, Kansas, 66762, United States
Salina Regional Health Center
Salina, Kansas, 67401, United States
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, 66606, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
University Health Truman Medical Center
Kansas City, Missouri, 64108, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Anna Spreafico
University Health Network Princess Margaret Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 24, 2019
First Posted
January 25, 2019
Study Start
December 9, 2019
Primary Completion (Estimated)
January 31, 2027
Study Completion (Estimated)
January 31, 2027
Last Updated
May 13, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page