Vilastobart+Retifanlimab in BRCA or PALB2 Deficient PC

NCT07765836 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 26-466
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm, open-label, non-randomized multi-institution phase II trial of a Fc enhanced CTLA4 antibody, vilastobart, in combination with PD-1 antibody, retifanlimab, in patients with BRCA1, BRCA2 or PALB2 deficient pancreatic cancer (PC).

Conditions

Pancreatic Cancer Metastatic

Keywords

BRCA1, BRCA2, or PALB2 mutation; metastatic pancreatic cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  The primary endpoint is objective response rate for combination of vilastobart with retifanlimab. Response is measured using RECISTv1.1 and evaluated independently. Evaluation of the primary endpoint will follow a Simon's two-stage design. The objective response rate will be reported with an exact binomial 95% confidence interval.

  Up to 1 year from baseline.

Secondary Outcomes (6)

• Progression free survival (PFS)

  From Day 1 through end of follow up (up to 3 years from registration)

• Overall survival (OS)

  Up to 3 years from registration

• Duration of response (DoR)

  From Day 1 through end of follow up (up to 3 years from registration)

• Overall clinical benefit

  From baseline through up to 1 year.

• Safety and tolerability of vilastobart and retifanlimab

  From baseline through up to 1 year

Study Arms (1)

Vilastobart + Retifanlimab

EXPERIMENTAL

This arm involves screening, study treatment with the study drugs, study visits, and follow-up visits for up to 3 years from time of joining study. Participants will receive up to 4 doses of Vilastobart, and Retifanlimab every three weeks until disease progression, intolerable side effects, or for a total of one year. Premedication for all vilastobart doses is required. For participants who experience disease progression on retifanlimab monotherapy or after completion of therapy on trial may be considered for re-induction with vilastobart and retifanlimab. Treatment beyond disease progression will be permitted for first instance of progressive disease by RECIST only if patients remain clinically stable from their disease and ongoing treatment is considered appropriate by patient, treating physician, and Sponsor Investigator.

Drug: vilastobart (XTX101); Drug: Retifanlimab

Interventions

vilastobart (XTX101) DRUG

100mg administered once every 6 weeks (Day 1 of every 6-week cycle) by intravenous infusion (IV) over about 90-140 minutes. This will continue for up to 4 6-week cycles (4 doses).

Also known as: XTX101

Vilastobart + Retifanlimab

Retifanlimab DRUG

375 mg administered once every 3 weeks (Days 2 and 23 of every 6-week cycle) by intravenous infusion over about 30 minutes. This will continue for up to 12 months.

Also known as: INCMGA00012, MGA012, ZYNYZ

Vilastobart + Retifanlimab

Eligibility Criteria

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

You may qualify if:

• Participant must have histologically proven metastatic pancreatic cancer. Histologies including acinar cell carcinoma, carcinoma, ductal carcinoma, ductal adenocarcinoma, poorly differentiated or adenosquamous carcinoma are allowed.
• Participant must have a germline or somatic pathogenic alteration in BRCA1, BRCA2, or PALB2 on tumor next generation sequencing (NGS) performed using a CLIA certified assay. Somatic pathogenic alterations detected on circulating tumor DNA need confirmation on tumor tissue NGS. Germline pathogenic alterations in BRCA1, BRCA2 or PALB2 do not require further confirmation on tumor NGS. All genomic reports be verified in writing (via email) by site and/or overall PI.
• Participants must have measurable disease per RECIST version 1.1.
• Participant must have at least one disease site which is amenable to safe biopsy and must agree to pre- and on-treatment biopsies (core, incisional, or excisional biopsy) of tumor site. In select cases biopsies can be waived after discussion with the Sponsor Investigator.
• Participant must have had at least one but not more than two lines of cytotoxic chemotherapy for metastatic disease. Receipt of neoadjuvant or adjuvant therapy within the last 12 months may count as one line of therapy in metastatic setting for patients with recurrent disease who are being considered for the study. Receipt of targeted therapy such as KRAS inhibitor, or PARP inhibitor is not counted line of therapy. Recycling of the same agents from prior lines of cytotoxic chemotherapy after disease progression does not count as a new line of therapy.
• Participant must have had prior platinum containing chemotherapy with at least a best response of stable disease. Participants with primary disease progression on platinum chemotherapy are ineligible.
• Age ≥18 years
• ECOG performance status of 0-2.
• Participants must meet the following organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/mcL
• platelets ≥75,000/mcL
• total bilirubin ≤ 1.5x institutional upper limit of normal (ULN). For patients with liver metastases or confirmed/suspected Gilbert syndrome, total bilirubin ≤ 3 × ULN
• AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN. For patients with liver metastases, AST and ALT ≤ 5 × ULN
• glomerular filtration rate (GFR) ≥30 mL/min/1.73 m\^2
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

You may not qualify if:

• Participants with neuroendocrine tumors of the pancreas are excluded.
• Prior anticancer therapy:
• Received prior treatment with anti-CTLA-4 therapy
• Received prior immune-checkpoint anti-PD-1/PD-L1 therapy
• Received prior approved systemic anticancer therapy within 2 weeks or within its 5 half-lives prior to study treatment, whichever is shorter. Note: Long-standing hormonal therapy for prostate, breast, uterine, and adrenal cancer may be permitted to continue if it is deemed to be in the best interest of the patient, after discussion with the Sponsor Investigator.
• Received prior radiotherapy within 2 weeks prior to study treatment. Note: Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia or stable, Grade ≤ 2 non-autoimmune chemotherapy-induced peripheral neuropathy.
• Participants with uncontrolled intercurrent illness that would interfere with ability to participate in the opinion of the treating investigator.
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• Has an active infection requiring systemic intravenous or oral therapy within 7 days of cycle 1 day 1.
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of trial treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. COVID-19 vaccination should not be given within 7 days of trial drug initiation.
• Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (\> 10 mg/day of prednisone or equivalent).
• Physiologic corticosteroid replacement therapy at doses ≤ 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted.
• Participants with asthma that requires intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections may participate.
• Participants using topical, ocular, intra-articular, or intranasal corticosteroids (with minimal systemic absorption) may participate.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Xilio Development, Inc.: collaborator
• Incyte Corporation: collaborator
• Lustgarten Foundation: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Fanconi Anemia, Complementation Group D1; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Harshabad Singh, MBBS MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Harshabad Singh, MBBS MD

CONTACT

617-724-4000; sharshabad@mgb.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 10, 2026
• First Posted: August 14, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: August 14, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)