Clinical trial NCT06704724: A Study to Learn About the Study Medicine PF-07985045 When Given Alone or With Other Anti-cancer Therapies in People With Advanced Solid Tumors That Have a Change in a Gene.
Official title: A PHASE 1 OPEN-LABEL STUDY OF PF-07985045 AS A SINGLE-AGENT AND IN COMBINATION WITH OTHER ANTI-CANCER AGENTS IN PARTICIPANTS WITH ADVANCED SOLID TUMORS
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Carcinoma, Pancreatic Ductal
Colorectal Neoplasms
Carcinoma, Non-Small-Cell Lung
Keywords: Carcinoma, Pancreatic Ductal
Carcinoma, Ductal, Pancreatic
Duct-Cell Carcinoma of the Pancreas
Duct-Cell Carcinoma, Pancreas
Ductal Carcinoma of the Pancreas
Pancreatic Duct Cell Carcinoma
Pancreatic Ductal Carcinoma
pancreatic ductal adenocarcinoma
PDAC
Colorectal Neoplasms
Colorectal Cancer
Colorectal Carcinoma
Colorectal Tumors
Neoplasms, Colorectal
Rectal Cancer
Colon Cancer
CRC
MSS CRC
Carcinoma, Non-Small-Cell Lung
Non-Small Cell Lung Cancer
Non-Small Cell Lung Carcinoma
Non-Small-Cell Lung Carcinoma
Nonsmall Cell Lung Cancer
Lung Cancer
NSCLC
KRAS
KRAS gene mutation
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2024-11-26
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to learn about the safety and effects of the study medicine when given alone or together with other anti-cancer therapies. Anti-cancer therapy is a type of treatment to stop the growth of cancer.

This study also aims to find the best amount of study medication.

This study is seeking participants who have solid tumors (a mass of abnormal cells that forms a lump or growth in the body) that:

* are advanced (cancer that doesn't disappear or stay away with treatment) and
* have a KRAS gene mutation (a change in the DNA of the KRAS gene that can cause cells to grow in very high numbers).

This includes (but limited to) the following cancer types:

* Non-Small Cell Lung Cancer (NSCLC): It's a type of lung cancer where the cells grow slowly but often spread to other parts of the body.
* Colorectal Cancer (CRC): This is a disease where cells in the colon (a part of large intestine) or rectum grow out of control.
* Pancreatic ductal adenocarcinoma (PDAC): This is a cancer that starts in the ducts of the pancreas but can spread quickly to other parts of the body. Pancreas is a long, flat gland that lies in the abdomen behind the stomach. Pancreas creates enzymes that help with digestion. It also makes hormones that can help control your blood sugar levels.

All participants in this study will take the study medication (PF-07985045) as pill by mouth once a day. This will be repeated for 21-day or 28-day cycles.

Depending on which part of the study participants are enrolled into they will receive the study medication (PF-07985045 alone or in combination with other anti-cancer medications). These anti-cancer medications will be given in the study clinic by intravenous (IV) that is directly injected into the veins at different times (depending on the treatment) during the 21-day or 28-day cycle.

Participants can continue to take the study medication (PF-07985045) and the combination anti-cancer therapy until their cancer is no longer responding.

The study will look at the experiences of people receiving the study medicines. This will help see if the study medicines are safe and effective.

Participants will be in this study for up to 4 years. During this time, the participants will come into the clinic for 1 to 4 times in each 21-day or 28-day cycle. After the participants have stopped taking the study medication (at about at 2 years) they will be followed for another two years to see how they are doing


Eligibility criteria: Inclusion Criteria:

* Histological or cytological diagnosis of advanced, unresectable, and/or metastatic or relapsed/refractory solid tumor.

  * Note for PDAC: Only participants with the histologic type of adenocarcinoma of the pancreas are allowed to enroll. For PDAC, if loco-regional disease is present, must also have metastatic disease.
  * Note for NSCLC: If a driver mutation is present, the participant was resistant or intolerant of precision medicine therapy (eg, inhibitors of EGFR, ALK, ROS1, or others).
* ECOG PS 0 or 1
* Presence of at least 1 measurable lesion based on RECIST version 1.1 that has not been previously irradiated.
* Documentation of mutated KRAS gene

  1. KRAS mutations of any variant except previously treated G12C, present in tumor tissue or blood
  2. If the participant received KRAS G12C inhibitor treatment previously, the KRAS mutation status must be other than G12C
* Part 1: Participant must have progressed on standard treatment(s) for which no additional, effective therapy is available.

  1. PDAC (2-3L): Participants must have received and radiologically progressed on prior lines of systemic therapy for metastatic pancreatic adenocarcinoma. If participants received prior neoadjuvant or adjuvant chemotherapy and progressed within 6 months of the last dose, then this should be considered as a prior line of systemic therapy.
  2. NSCLC (2-3L): Participants must have received prior lines of anti-cancer treatment and progressed on at least a platinum-containing chemotherapy regimen and checkpoint inhibitor therapy; for participants with EGFR, ALK, or other genomic tumor alterations, participants must have progressed on approved therapy for these alterations.
  3. CRC (2-3L): Participants must have had one or two prior systemic treatment regimens for mCRC. For either one or two prior treatments, these regimens must have included a fluoropyrimidine, oxaliplatin, or irinotecan; for one prior treatment, exposure to VEGF/VEGF receptor (VEGFR) inhibitor is optional.
  4. other tumors: Participants, in the judgment of the investigator, must have progressed or become intolerant to all available standard therapies, or have refused such therapy.
* Part 2:

  1. PDAC (1L) Cohort A2: Participants must not have received prior chemotherapy for metastatic disease. Participant could have received neoadjuvant therapy, adjuvant therapy, or adjuvant chemo-radiotherapy, as long as relapse did not occur within 6 months of completing these forms of adjuvant treatment. If so, the relapse within 6 months would be considered a line of therapy; the participant would be considered 2L, and not 1L.
  2. CRC (2-3L) Cohort B2: Participants must have had one or two prior systemic treatment regimens for mCRC. For either one or two prior treatments, these regimens must have included a fluoropyrimidine, irinotecan, oxaliplatin; for one prior treatment, exposure to a VEGF/VEGF receptor (VEGFR) inhibitor is optional.
  3. CRC (1L) Cohort B3: Participants must not have had prior chemotherapy for advanced or metastatic disease. Participant could have received adjuvant chemotherapy or adjuvant chemo-radiotherapy, as long as relapse did not occur within 6 months of complete of adjuvant therapy. If so, the relapse within 6 months would be considered a line of therapy; the participant would be considered 2L, and not 1L.
  4. NSCLC (1L) Cohort C2: Participants must have a TPS ≥50% and must not have received prior systemic treatment setting.
  5. NSCLC (1L) Cohort C3: Participants with any TPS and must not have received prior systemic treatment setting.

Exclusion Criteria:

* Active or history of pneumonitis/ILD, pulmonary fibrosis requiring treatment with systemic steroid therapy, including evidence to suggest pneumonitis/ILD on baseline assessments including imaging.
* Diagnosis of immunodeficiency or an active autoimmune disease that require systemic treatment with chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy in the past 2 years.
* Sensory peripheral neuropathy ≥Grade 2 (Part 2 only)
* Active or history of clinically significant gastrointestinal (GI) disease (including but not limited to inflammatory GI disease \[eg, ulcerative colitis, Crohn's disease, inflammatory bowel disease\], immune-mediated colitis, peptic ulcer disease, GI bleeding, chronic diarrhea) and other conditions that are unresolved and/or may increase the risk associated with study participation or study treatment administration.
* Active bleeding disorder, including GI bleeding, as evidenced by hematemesis, significant hemoptysis or melena in the past 6 months.
* Major surgery or completion of radiation therapy ≤4 weeks prior to enrollment/randomization or radiation therapy that included \>30% of the bone marrow.
* Known sensitivity or contraindication to any component of study intervention (PF-07985045, gemcitabine, nab-paclitaxel, cetuximab, bevacizumab, FOLFOX, 5-FU, pembrolizumab, sasanlimab, cisplatin, carboplatin, pemetrexed, SHP2 inhibitor(s).
* Hematologic abnormalities.
* Renal impairment.

  * Hepatic abnormalities.

Primary outcomes:
measure: Part 1 & 2: Incidence of Adverse Events (AEs)
timeFrame: Start of treatment up to 30 days after last dose or start of new anticancer therapy (whichever occurs first)
measure: PART 1 & 2: Number of participants with laboratory abnormalities
timeFrame: From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first
measure: Part 1 & Part 2 (Dose Escalation Only): Number of participants with Dose-limiting toxicities (DLT)
timeFrame: Baseline up to 28 days
measure: Part 2: Objective Response - Number of Participants With Objective Response (alone or in combination)
timeFrame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years'
Secondary outcomes:
measure: Part 1 & 2: Maximum Observed Serum Concentration (Cmax)
timeFrame: baseline through end of Cycle 1 (All cycles are 28 days except Part 2 Cohort C2/C3 which are 21 days)
measure: Part 1& 2: Time to Reach Maximum Observed Serum Concentration (Tmax)
timeFrame: Baseline through end of Cycle 1 (All cycles are 28 days except part 2 Cohort C2/C3 which are 21 days)
measure: Part 1 & 2: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: Baseline through end of Cycle 1 (All cycles are 28 days except Part 2 Cohort C2/C3 which are 21 days)
measure: Part 1 & 2: Changes in pERK levels
timeFrame: Baseline through end of Cycle 1 (All cycles are 28 days except Part 2 Cohort C2/C3 which are 21 days)
measure: Objective Response - Number of Participants With Objective Response
timeFrame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years
measure: Part 1: Effect of Food on Cmax
timeFrame: Baseline through end of Cycle 1 (All cycles are 28 days)
measure: Part 1: Effect of Food on Tmax
timeFrame: Baseline through end of Cycle 1 (All cycles are 28 days)
measure: Part 1: Effect of Food on AUClast
timeFrame: Baseline through end of Cycle 1 (All cycles are 28 days)
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Rogers
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Duarte
country: United States
facility: City of Hope (City of Hope National Medical Center, City Of Hope Medical Center)
state: California
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Newton
country: United States
facility: DFCI Chestnut Hill
state: Massachusetts
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: