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.

Prior treatment

• Active pneumonitis/ILD, pulmonary fibrosis requiring treatment with systemic steroid therapy. Additionally, participants in IO combinations (Cohorts C2 and C3) with history and/or active pneumonitis/ILD or pulmonary fibrosis requiring steroids are excluded from enrollment.
• Major surgery or completion of radiation therapy ≤4 weeks prior to enrollment/randomization or radiation therapy that included >30% of the bone marrow.
• Current use or have received PPIs in the last seven days prior to starting study treatment.
• 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).

Other illness

• 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.
• Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including drainage catheter placement, therapeutic thoracentesis or abdominal paracentesis) is eligible.
• Renal impairment.

Other

• Hematologic abnormalities.
• Hepatic abnormalities.

• 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
  • KRAS mutations of any variant except previously treated with any KRAS inhibitor
• Part 1: Participant must have progressed on standard treatment(s) for which no additional, effective therapy is available.
  • 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.
  • NSCLC (2-3L): Participants must have received prior lines of anti-cancer treatment and progressed on at least a platinum-containing chemotherapy regimen and/or checkpoint inhibitor therapy; for participants with EGFR, ALK, or other genomic tumor alterations, participants must have progressed on approved therapy for these alterations.
  • CRC (2-3L): Participants must have had only 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.
  • 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:
  • 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.
  • 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.
  • 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.
  • NSCLC (1L) Cohort C2: Participants must have a TPS ≥50% and must not have received prior systemic treatment setting.
  • NSCLC (1L) Cohort C3: Participants with any TPS and must not have received prior systemic treatment setting.